Muscle Invasive Bladder Cancer Articles

Articles

  • A Multicenter Study Evaluating Safety and Efficacy of TAR-200 in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Ineligible for or Refuse Cisplatin-based Chemotherapy and Who Are Unfit for Radical Cystectomy

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    A Multicenter Study Evaluating Safety and Efficacy of TAR-200 in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Ineligible for or Refuse Cisplatin-based Chemotherapy and Who Are Unfit for Radical Cystectomy


    Condition: Bladder Cancer TNM Staging Primary Tumor (T) T2A, Bladder Cancer TNM Staging Primary Tumor (T) T2B, Bladder Cancer TNM Staging Primary Tumor (T) T3A, Bladder Cancer TNM Staging Primary Tumor (T) T3B

    Intervention:

    • Drug: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200

    Purpose: The purpose of this study is to determine if TAR-200, an investigational drug-delivery system, is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) who are unfit for radical cystectomy (RC) during an 84-day induction period comprised of four consecutive 21-day dosing cycles.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03404791

    Sponsor: Taris Biomedical LLC

    Primary Outcome Measures:

    • Measure: Number of participants with incidence of treatment emergent adverse events (TEAEs) over 4 consecutive 21-day dosing cycles of TAR-200 as assessed by CTCAE V4.0
    • Time Frame: Study Day 0 to Study Day 84
    • Safety Issue:
    • Measure: Number of participants that do not require TAR-200 removal prior to the scheduled date of removal due to meeting any of the Subject Stopping Safety Criteria or other drug or device related AE
    • Time Frame: Study Day 0 to Study Day 84
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Proportion of subjects with clinical complete response (cCR)
    • Time Frame: Approximately Study Day 0 to Study Day 360
    • Safety Issue:
    • Measure: Proportion of subjects with clinical partial response (cPR)
    • Time Frame: Approximately Study Day 0 to Study Day 360
    • Safety Issue:
    • Measure: Proportion of subjects with stable disease (SD)
    • Time Frame: Approximately Study Day 0 to Study Day 360
    • Safety Issue:
    • Measure: Proportion of subjects with progression
    • Time Frame: Approximately Study Day 0 to Study Day 360
    • Safety Issue:
    • Measure: Symptom control
    • Time Frame: Approximately Study Day 0 to Study Day 360
    • Safety Issue:
    • Measure: Time to intervention for symptom control
    • Time Frame: Approximately Study Day 0 to Study Day 360
    • Safety Issue:
    • Measure: Time to progression
    • Time Frame: Approximately Study Day 0 to Study Day 360
    • Safety Issue:
    • Measure: Proportion of subjects undergoing post-treatment interventions by 3, 6, 9, and 12 months
    • Time Frame: Approximately Study Day 0 to Study Day 360
    • Safety Issue:
    • Measure: Proportion of subjects surviving at 12 months
    • Time Frame: Approximately Study Day 0 to Study Day 360
    • Safety Issue:

    Estimated Enrollment: 30

    Study Start Date: January 26, 2018

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    1. Histological proof of non-metastatic muscle-invasive urothelial cell carcinoma of the bladder.
    2. Subject must have been as fully resected as possible per the physician's judgment.
    3. Subjects must be deemed unfit for RC due to comorbid conditions with a risk of mortality.
    4. Subjects must refuse or be deemed ineligible for cisplatin-based chemotherapy.
    5. Subject must refuse or not be eligible for radiotherapy.
    6. Life expectancy of at least 4 months.
    7. Adequate bone marrow, liver, and renal function.
    8. Subjects must be willing to undergo a cystoscopy.
    9. Subjects must be willing to undergo a biopsy for assessment of clinical response.
    10. Written informed consent and authorization for release of personal health information obtained according to local laws.
    11. Age ≥18 years at the time of informed consent.
    12. Females of childbearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 4 weeks after treatment discontinuation. Subject's partner must also use barrier protection while subject is on study until 4 weeks after treatment discontinuation.
    13. Males must be willing to use an effective method of contraception/method to avoid seminal transfer (barrier method or abstinence) from the time consent is signed until 4 weeks after treatment discontinuation. Subject's partner must also use barrier protection while subject is on study until 4 weeks after treatment discontinuation.
    14. Females of childbearing potential must have a negative pregnancy test within 21 days prior to Study Day 0.

    Exclusion Criteria:

    1. Other active malignancies.
    2. Presence of any bladder or urethral anatomic feature that in the opinion of the Investigator may prevent the safe placement, indwelling use, or removal of TAR-2
    3. Pyeloureteral tube externalized to the skin (ureteral stent or unilateral nephrostomy tube is allowed).
    4. Evidence of bladder perforation during diagnostic cystoscopy.
    5. Bladder post-void residual volume (PVR) of >750 mL.
    6. Concurrent clinically significant infections as determined by the treating Investigator.
    7. Known hypersensitivity to gemcitabine (or other drug excipients) or chemically related drugs.
    8. Known hypersensitivity to the device constituent or TARIS Inserter materials.
    9. Use of an investigational product within 30 days or 5 half-lives, whichever is longer, preceding Study Day
    10. Female subject who is lactating/breastfeeding.
    11. Difficulty providing blood samples.
    12. Unwilling or unable to provide informed consent or comply with the requirements of this protocol, including the presence of any condition (physical, mental or social) that is likely to affect the subject's return for scheduled visits and follow-up.
    13. Other unspecified reasons that, in the opinion of the Investigator, make the subject unsuitable for enrollment.

    Contact:

    • TARIS Biomedical LLC
    • +1-971-676-7750

    Locations:

    • Mayo Clinic
    • Phoenix Arizona 85054 United States
    • Chesapeake Urology
    • Hanover Maryland 21076 United States
    • Michigan Institute of Urology
    • Troy Michigan 48084 United States
    • University of Rochester Medical Center
    • Rochester New York 14642 United States
    • Urology Associates of Nashville
    • Nashville Tennessee 37209 United States
    • Vanderbilt University Medical Center
    • Nashville Tennessee 37232 United States
    • North Austin Urology
    • Austin Texas 78750 United States
    • Urology of Virginia
    • Virginia Beach Virginia 23462 United States
    • Fundacion Puigvert
    • Barcelona Spain
    • Hospital Universitario 12 de Octubre
    • Madrid Spain
    • Instituto Valenciano de Oncologia
    • Valencia Spain

    View trial on ClinicalTrials.gov


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    Published July 12, 2019
  • A Multicenter Study of TAR-200 in Combination With Nivolumab (OPDIVO) in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Scheduled for Radical Cystectomy and Are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy

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    A Multicenter Study of TAR-200 in Combination With Nivolumab (OPDIVO) in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Scheduled for Radical Cystectomy and Are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy


    Condition: Bladder Cancer TNM Staging Primary Tumor (T) T2, Bladder Cancer TNM Staging Primary Tumor (T) T2A, Bladder Cancer TNM Staging Primary Tumor (T) T2B, Bladder Cancer TNM Staging Primary Tumor (T) T3, Bladder Cancer TNM Staging Primary Tumor (T) T3A, Bladder Cancer TNM Staging Primary Tumor (T) T3B, Bladder Cancer TNM Staging Regional Lymph Node (N) N0, Bladder Cancer TNM Staging Regional Lymph Node (N) N1, Bladder Cancer TNM Staging Distant Metastasis (M) M0

    Intervention:

    • Drug: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200
    • Drug: Nivolumab Injection [Opdivo]

    Purpose: The purpose of this study is to determine if TAR-200, an investigational drug delivery system, in combination with nivolumab is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) who are scheduled for radical cystectomy (RC) during an 84-day dosing cycle induction period comprised of four consecutive 21-day dosing cycles.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03518320

    Sponsor: Taris Biomedical LLC

    Primary Outcome Measures:

    • Measure: Number of participants with incidence of treatment emergent adverse events (TEAEs) over 4 consecutive 21-day dosing cycles of TAR-200 in combination with Nivolumab as assessed by CTCAE V4.0.
    • Time Frame: Study Day 0 to Study Day 180
    • Safety Issue:
    • Measure: Number of participants that do not require treatment discontinuation prior to the scheduled end date due to meeting any of the Subject Stopping Safety criteria or other drug or device related AE
    • Time Frame: Study Day 0 to Study Day 180
    • Safety Issue:

    Estimated Enrollment: 25

    Study Start Date: January 2, 2019

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • 1. Histological proof of muscle-invasive urothelial carcinoma of the bladder (stage cT2-cT3b, N0-1, M0). Subjects with mixed histology are required to have documented dominant transitional cell pattern with no more than 10% squamous differentiation and 10% glandular differentiation. Micropapillary/sarcomatoid/adenocarcinoma/plasmacytoid variants are not allowed. 2. Subjects with a total tumor size of ≤2 cm following TURBT are eligible. Subjects with a tumor or tumors totaling >2 cm at screening must undergo a second debulking TURBT to reduce the tumor(s) to ≤2 cm to be eligible for treatment. 3. Adequate bone marrow, liver, and renal function, as documented by the following laboratory assessments conducted within 28 days prior to dosing:
    • Hemoglobin ≥9.0 g/dL
    • Absolute neutrophil count (ANC) ≥1,500/mm3
    • Platelet count ≥100,000/mm3
    • Total bilirubin ≤1.5x upper limit of normal (ULN)
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5x ULN
    • Glomerular filtration rate (GFR) ≥30 ml/min/1.73 m2 (assessed using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) 4. Willing to undergo multiple cystoscopies during the study for TAR-200 removal and post-insertion examination. 5. Deemed eligible for and willing to undergo RC by the attending urologist. 6. Subjects must refuse cisplatin-based combination chemotherapy (and understand the risk and benefits of doing so) or be deemed ineligible for cisplatin-based chemotherapy by meeting at least one of the following criteria:
    • GFR <60 mL/min/1.73 m2 (assessed using the CKD-EPI equation)
    • Common Terminology Criteria for Adverse Events (CTCAE) v4 Grade ≥2 audiometric hearing loss
    • CTCAE v4 Grade ≥2 peripheral neuropathy 7. Prior systemic chemotherapy for indications other than urothelial cell carcinoma of the bladder is permitted. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (National Cancer Institute CTCAE version 4.03) or baseline before administration of study drug. Participants with toxicities attributed to prior anti cancer therapy which are not expected to resolve and result in long lasting sequelae, such as peripheral neuropathy after platinum-based therapy or audiometric hearing loss, are permitted to enroll. 8. Written informed consent and authorization for release of personal health information obtained according to local laws. 9. Age ≥18 years at the time of consent. 10. Women of childbearing potential (WOCBP) must be willing to use a highly effective method of contraception (hormonal or intrauterine device [IUD] method of birth control with a failure rate of <1% when used consistently and correctly; or abstinence) for the duration of treatment with TAR-200 in combination with nivolumab plus 5 half-lives of study treatment, plus 30 days (duration of ovulatory cycle), for a total of 5 months post treatment completion. Note: WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements, but still must undergo pregnancy testing as described in this protocol. 11. WOCBP must have a negative pregnancy test within 24 hours prior to Study Day 0. 12. Males must be willing to use an effective method of contraception to avoid seminal transfer (double barrier method) or abstinence for the duration of treatment with TAR 200 in combination with nivolumab plus 5 half-lives of the study treatment, plus 90 days (duration of sperm turnover), for a total of 7 months post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time. 13. Azoospermic males should also use double barrier contraceptive methods to avoid contamination of the non-treatment sexual partner. Exclusion Criteria: 1. Active malignancies within 3 years except for those with a negligible risk of metastasis or death treated with expected curative outcome. 2. Prior systemic chemotherapy for urothelial cell carcinoma of the bladder. 3. Prior treatment with an anti-programmed death-1 (PD-1), anti-PD-L1, anti PD L2, anti-CD137, or anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co stimulation or checkpoint pathways. 4. Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis. 5. Subjects who require immunosuppressive medications such as methotrexate, tumor necrosis factor inhibitors, or systemic corticosteroids (>10 mg/day prednisone equivalents) within 2 weeks prior to study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 6. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 7. Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use, or removal of TAR 200. 8. Pyeloureteral tube externalized to the skin is exclusionary. Unilateral nephrostomy tube or ureteral stent is permitted as long as it does not interfere with placement or retention of TAR-200 in the bladder. 9. Indwelling catheters are not permitted. 10. Subjects with evidence of bladder perforation during diagnostic cystoscopy may be treated if perforation has resolved prior to dosing. 11. Bladder post-void residual volume of >500 mL. 12. History of diagnosis of neurogenic bladder requiring intermittent catheterization. 13. Active, uncontrolled urogenital bacterial, viral or fungal infections, including urinary tract infection (UTI). Skin/nail fungal infections are not exclusionary. Subjects with active shingles (varicella zoster infection) will be excluded from the study. 14. Subjects with a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus RNA or hepatitis C antibody (HCV antibody) indicating acute or chronic infection. 15. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Note: Testing for HIV must be performed at sites where mandated locally. 16. Uncontrolled adrenal insufficiency. 17. New York Heart Association Functional Classification of Heart Failure: Class III or IV (Appendix 1). 18. Eastern Cooperative Oncology Group (ECOG) performance status ≥2. 19. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements. 20. Subjects who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation. 21. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity. 22. Subjects must have recovered from the effects of major surgery requiring general anesthetic or significant traumatic injury at least 14 days before Study Day 0. 23. History of allergy or hypersensitivity to gemcitabine (or other drug excipients in TAR-200) or drugs chemically-related to gemcitabine. 24. History of allergy or hypersensitivity to the device constituent or Inserter materials. 25. History of allergy or hypersensitivity to nivolumab drug components. 26. Female subject who is pregnant (as verified by urine test at time of screening) or lactating or of childbearing potential and not using acceptable methods of contraception. 27. Difficulty providing blood samples. 28. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent. 29. Use of an investigational product (IP) within 30 days or 5 half-lives, whichever is longer, preceding Study Day 0. 30. Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and sponsor approval is required.) 31. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness Other protocol defined inclusion/

    Exclusion Criteria:

    1. Active malignancies within 3 years except for those with a negligible risk of metastasis or death treated with expected curative outcome.
    2. Prior systemic chemotherapy for urothelial cell carcinoma of the bladder.
    3. Prior treatment with an anti-programmed death-1 (PD-1), anti-PD-L1, anti PD L2, anti-CD137, or anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co stimulation or checkpoint pathways.
    4. Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis.
    5. Subjects who require immunosuppressive medications such as methotrexate, tumor necrosis factor inhibitors, or systemic corticosteroids (>10 mg/day prednisone equivalents) within 2 weeks prior to study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
    6. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
    7. Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use, or removal of TAR 2
    8. Pyeloureteral tube externalized to the skin is exclusionary. Unilateral nephrostomy tube or ureteral stent is permitted as long as it does not interfere with placement or retention of TAR-200 in the bladder.
    9. Indwelling catheters are not permitted.
    10. Subjects with evidence of bladder perforation during diagnostic cystoscopy may be treated if perforation has resolved prior to dosing.
    11. Bladder post-void residual volume of >500 mL.
    12. History of diagnosis of neurogenic bladder requiring intermittent catheterization.
    13. Active, uncontrolled urogenital bacterial, viral or fungal infections, including urinary tract infection (UTI). Skin/nail fungal infections are not exclusionary. Subjects with active shingles (varicella zoster infection) will be excluded from the study.
    14. Subjects with a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus RNA or hepatitis C antibody (HCV antibody) indicating acute or chronic infection.
    15. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Note: Testing for HIV must be performed at sites where mandated locally.
    16. Uncontrolled adrenal insufficiency.
    17. New York Heart Association Functional Classification of Heart Failure: Class III or IV (Appendix 1).
    18. Eastern Cooperative Oncology Group (ECOG) performance status ≥
    19. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
    20. Subjects who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
    21. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
    22. Subjects must have recovered from the effects of major surgery requiring general anesthetic or significant traumatic injury at least 14 days before Study Day
    23. History of allergy or hypersensitivity to gemcitabine (or other drug excipients in TAR-200) or drugs chemically-related to gemcitabine.
    24. History of allergy or hypersensitivity to the device constituent or Inserter materials.
    25. History of allergy or hypersensitivity to nivolumab drug components.
    26. Female subject who is pregnant (as verified by urine test at time of screening) or lactating or of childbearing potential and not using acceptable methods of contraception.
    27. Difficulty providing blood samples.
    28. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
    29. Use of an investigational product (IP) within 30 days or 5 half-lives, whichever is longer, preceding Study Day
    30. Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and sponsor approval is required.)
    31. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness Other protocol defined inclusion/exclusion criteria could apply.

    Contact:

    • TARIS Biomedical LLC
    • +1-781-676-7750

    Locations:

    • DuPage Medical Group
    • Hinsdale Illinois 60521 United States
    • University of Rochester Medical Center
    • Rochester New York 14642 United States
    • Duke University Medical Center
    • Durham North Carolina 27710 United States
    • The University of Oklahoma Stephenson Cancer Center
    • Oklahoma City Oklahoma 73104 United States
    • Thomas Jefferson University
    • Philadelphia Pennsylvania 19107 United States
    • Vanderbilt University Medical Center
    • Nashville Tennessee 37232 United States

    View trial on ClinicalTrials.gov


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    Published October 13, 2018
  • A Phase 1b, Multicenter, Open Label Study Evaluating Safety, Tolerability and Preliminary Efficacy of GemRIS 225 mg in Subjects With Muscle-Invasive Transitional Cell Carcinoma of the Bladder

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    A Phase 1b, Multicenter, Open Label Study Evaluating Safety, Tolerability and Preliminary Efficacy of GemRIS 225 mg in Subjects With Muscle-Invasive Transitional Cell Carcinoma of the Bladder


    Condition: Urinary Bladder Cancer

    Intervention:

    • Drug: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200

    Purpose: The purpose of this study is to determine if TAR-200, an investigational drug-delivery system, is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) between diagnosis and radical cystectomy (RC).

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02722538

    Sponsor: Taris Biomedical LLC

    Primary Outcome Measures:

    • Measure: Number of participants with treatment emergent adverse events (TEAEs) coded with MedDRA and graded for severity with CTCAE v4.0
    • Time Frame: Maximum 132 days
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Number of participants who are tolerant of TAR-200 indwelling
    • Time Frame: From Day 0 up to Day 7
    • Safety Issue:
    • Measure: Percentage of participants who are tolerant of TAR-200 indwelling
    • Time Frame: From Day 0 up to Day 7
    • Safety Issue:
    • Measure: Number of participants who are tolerant of TAR-200 indwelling
    • Time Frame: From Day 21 up to Day 28
    • Safety Issue:
    • Measure: Percentage of participants who are tolerant of TAR-200 indwelling
    • Time Frame: From Day 21 up to Day 28
    • Safety Issue:
    • Measure: Cmax, plasma dFdU
    • Time Frame: From Day 0 up to Day 28
    • Safety Issue:
    • Measure: Tmax, plasma dFdU
    • Time Frame: From Day 0 up to Day 28
    • Safety Issue:
    • Measure: Cavg, plasma dFdU
    • Time Frame: From Day 0 up to Day 28
    • Safety Issue:
    • Measure: Cmax, plasma dFdC
    • Time Frame: From Day 0 up to Day 28
    • Safety Issue:
    • Measure: Tmax, plasma dFdC
    • Time Frame: From Day 0 up to Day 28
    • Safety Issue:
    • Measure: Cavg, plasma dFdC
    • Time Frame: From Day 0 up to Day 28
    • Safety Issue:
    • Measure: Cmax, urine dFdU (Arm 1 only)
    • Time Frame: From Day 0 up to Day 28
    • Safety Issue:
    • Measure: Tmax, urine dFdU (Arm 1 only)
    • Time Frame: From Day 0 up to Day 28
    • Safety Issue:
    • Measure: Cavg, urine dFdU (Arm 1 only)
    • Time Frame: From Day 0 up to Day 28
    • Safety Issue:
    • Measure: Cmax, urine dFdC (Arm 1 only)
    • Time Frame: From Day 0 up to Day 28
    • Safety Issue:
    • Measure: Tmax, urine dFdC (Arm 1 only)
    • Time Frame: From Day 0 up to Day 28
    • Safety Issue:
    • Measure: Cavg, urine dFdC (Arm 1 only)
    • Time Frame: From Day 0 up to Day 28
    • Safety Issue:
    • Measure: Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (AKT) (Arm 1)
    • Time Frame: Anti-tumor analysis will occur at study visit Day 28.
    • Safety Issue:
    • Measure: Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD31) (Arm 1)
    • Time Frame: Anti-tumor analysis will occur at study visit Day 28.
    • Safety Issue:
    • Measure: Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (Ki67) (Arm 1)
    • Time Frame: Anti-tumor analysis will occur at study visit Day 28.
    • Safety Issue:
    • Measure: Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (TUNEL) (Arm 1)
    • Time Frame: Anti-tumor analysis will occur at study visit Day 28.
    • Safety Issue:
    • Measure: Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD4) (Arm 1)
    • Time Frame: Anti-tumor analysis will occur at study visit Day 28.
    • Safety Issue:
    • Measure: Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD8) (Arm 1)
    • Time Frame: Anti-tumor analysis will occur at study visit Day 28.
    • Safety Issue:
    • Measure: Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (PD-L1) (Arm 1)
    • Time Frame: Anti-tumor analysis will occur at study visit Day 28.
    • Safety Issue:
    • Measure: Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (AKT) (Arm 2)
    • Time Frame: Anti-tumor analysis will occur at study visit Day 42.
    • Safety Issue:
    • Measure: Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD31) (Arm 2)
    • Time Frame: Anti-tumor analysis will occur at study visit Day 42.
    • Safety Issue:
    • Measure: Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (Ki67) (Arm 2)
    • Time Frame: Anti-tumor analysis will occur at study visit Day 42.
    • Safety Issue:
    • Measure: Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (TUNEL) (Arm 2)
    • Time Frame: Anti-tumor analysis will occur at study visit Day 42.
    • Safety Issue:
    • Measure: Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD4) (Arm 2)
    • Time Frame: Anti-tumor analysis will occur at study visit Day 42.
    • Safety Issue:
    • Measure: Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (CD8) (Arm 2)
    • Time Frame: Anti-tumor analysis will occur at study visit Day 42.
    • Safety Issue:
    • Measure: Preliminary anti-tumor effects assessed in tumor material (post-treatment) for immunohistochemical tissue biomarkers of drug-induced cell death (PD-L1) (Arm 2)
    • Time Frame: Anti-tumor analysis will occur at study visit Day 42.
    • Safety Issue:

    Estimated Enrollment: 26

    Study Start Date: May 2016

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histological proof of muscle-invasive transitional cell carcinoma of the bladder (stage II-III). Subjects with evidence of metastatic nodal disease to the obuturator or presacral lymph nodes only may be included (N1 M0). Subjects with any degree of fixation of the pelvic sidewall are not eligible.
    • In Arm 1, subjects must have residual visible tumor following TURBT. In Arm 2, subjects must be fully resected (i.e., no visible tumor or as little tumor as possible) after restaging TURBT 2-6 weeks prior to Study Day 0.
    • Adequate bone marrow, liver, and renal function, as assessed by the following requirements conducted within 21 days prior to dosing: 1. Hemoglobin ≥ 9.0 g/dL 2. Absolute neutrophil count (ANC) ≥ 1,500/mm3 3. Platelet count ≥ 100,000/mm3 4. Total bilirubin ≤ 1.5xULN (upper limit of normal) 5. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5xULN 6. Glomerular Filtration Rate (GFR) ≥ 30% (≥ 30 ml/min/1.73 m2)
    • Subjects must be willing to undergo a cystoscopy on study for investigational product removal.
    • Eligible for and willing to undergo RC per the attending urologist.
    • Subjects must be deemed ineligible for cisplatin-based combination chemotherapy by the attending medical oncologist.
    • Subjects medically eligible for neoadjuvant cisplatin-based combination chemotherapy who refuse this therapeutic option and understand the risks and benefits of doing so.
    • Prior radiation therapy is allowed provided that no radiation therapy was administered to the urinary bladder.
    • Written informed consent and Health Insurance Portability and Accountability Act of 1966 (HIPAA) authorization for release of personal health information.
    • Age > 18 years at the time of consent.

    Exclusion Criteria:

    • Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome.
    • Prior systemic chemotherapy for transitional cell carcinoma of the bladder. Any other prior systemic chemotherapy for a non-urothelial carcinoma must have been completed > 5 years prior to initiation of study.
    • Previous exposure to gemcitabine instillations.
    • Currently receiving other intravesical chemotherapy.
    • Concurrent clinically significant infections as determined by the treating investigator.
    • Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use or removal of TAR-200.
    • Documented history of vesicoureteral reflux or the presence of an indwelling ureteral stent or nephrostomy tube at the time of screening.
    • Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥ 6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis.
    • Bladder Post-Void Residual Volume (PVR) of > 250-mL.
    • Active, uncontrolled urogenital bacterial, viral or fungal infections, including urinary tract infection that in the opinion of the investigator, contraindicates participation. Skin/nail fungal infections are not exclusionary. Subjects with active shingles (varicella zoster infection) will be excluded from the study.
    • History or presence of any significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, gynecological, endocrine, immunological, dermatological, neurological or psychiatric disease or disorder that, in the opinion of the investigator, contraindicates participation.
    • History of diagnosis of neurogenic bladder.
    • Concomitant immunosuppressive medications, such as methotrexate or TNF inhibitors, within 2 weeks of Study Day 0, exclusive of steroid doses ≤ 5 mg daily.
    • Difficulty providing blood samples.
    • Unwilling or unable to provide informed consent or comply with the requirements of this protocol, including the presence of any condition (physical, mental or social) that is likely to affect the subject's return for scheduled visits and follow-up.
    • Other unspecified reasons that, in the opinion of the investigator or TARIS, make the subject unsuitable for enrollment.

    Contact:

    • TARIS Biomedical
    • 781-676-7750

    Locations:

    • University of Southern California Norris Comprehensive Cancer Center
    • Los Angeles California United States
    • University of Chicago Medical Center
    • Chicago Illinois United States
    • Johns Hopkins Hospital
    • Baltimore Maryland United States
    • Columbia University Medical Center
    • New York New York 10032 United States
    • Ohio State University Wexner Medical Center
    • Columbus Ohio United States
    • Radboudumc
    • Nijmegen Netherlands

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • A Phase 2 Study of Check Point Inhibitor, Durvalumab (Medi4736) for Bacillus Calmette-Guérin (BCG) Refractory Urothelial Carcinoma in Situ (CIS) of the Bladder

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    A Phase 2 Study of Check Point Inhibitor, Durvalumab (Medi4736) for Bacillus Calmette-Guérin (BCG) Refractory Urothelial Carcinoma in Situ (CIS) of the Bladder


    Condition: Carcinoma in Situ of Bladder, Bladder Cancer

    Intervention:

    • Drug: Durvalumab
    • Procedure: Cystoscopy with Biopsy

    Purpose: The purpose of this study is to test if an experimental drug called Durvalumab (Medi4736) given by intravenous (IV) infusion is effective in treating carcinoma in situ (CIS) of the bladder that no longer responds to Bacillus Calmette-Guérin (BCG) and to collect information on the safety of these drugs and whether they cause any side effects.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02901548

    Sponsor: H. Lee Moffitt Cancer Center and Research Institute

    Primary Outcome Measures:

    • Measure: Complete Response Rate at 6 Months
    • Time Frame: 6 Months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Complete Response Rate at 24 Months
    • Time Frame: 24 Months
    • Safety Issue:

    Estimated Enrollment: 34

    Study Start Date: February 16, 2017

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Must have pathologically confirmed urothelial carcinoma in situ (CIS) of the bladder that meet one of the following criteria: 1. Persistence of high-grade CIS at 6 months following an adequate course of BCG; OR
    • 2. Stage/grade progression at 3 months after induction BCG; OR
    • 3. Recurrence of high-grade CIS after achieving a disease-free state (i.e., CR) following induction of an adequate course of BCG that occurs < 9 months after the last exposure to BCG; OR
    • 4. Persistent CIS noted on the bladder biopsies within 3 months of completing at least 2 induction BCG (minimum of five weekly instillations). An adequate course of BCG should be defined as at least one course of induction (minimum of five weekly instillations) and one maintenance (two of three instillations) in a 6 months period, with an exception for any patient with grade/stage progression after induction BCG (minimum of five weekly instillations).
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
    • Adequate organ and marrow function.
    • Written informed consent and any locally required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
    • Females must not be pregnant, or breast feeding and must have a negative urine or serum pregnancy test within 28 days prior to treatment on day 1. Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from the time of screening, and must agree to continue using such precautions for 90 days after the final dose of Durvalumab. They must also refrain from egg cell donation for 90 days after the final dose of Durvalumab.
    • Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception and refrain from sperm donation from Day 1 through 90 days after receipt of the final dose of Durvalumab.

    Exclusion Criteria:

    • Muscle invasive (T2 or above) urothelial carcinoma or urothelial carcinoma outside the bladder.
    • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) or previous enrolment in the present study.
    • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
    • History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence; Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ.
    • Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, tyrosine kinase inhibitor, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 30 days prior to the first dose of study drug and within 6 weeks for nitrosourea, mitomycin C or intravesical therapy).
    • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction.
    • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
    • Any unresolved toxicity (CTCAE grade 2 or above) from previous anti-cancer therapy. [Potential participants with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy)].
    • Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
    • Active or prior documented autoimmune disease within the past 2 years. NOTE: Potential participants with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
    • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
    • History of primary immunodeficiency.
    • History of allogeneic organ transplant.
    • History of pneumonitis.
    • History of hypersensitivity to durvalumab or any excipient.
    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any participant known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the participant to give written informed consent.
    • Known history of previous clinical diagnosis of tuberculosis.
    • History of leptomeningeal carcinomatosis.
    • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab.
    • Females who are pregnant, breast-feeding or males or females of reproductive potential who are not employing an effective method of birth control.
    • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
    • Uncontrolled seizures.
    • Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.

    Contact:

    • Jingsong Zhang, M.D., Ph.D.
    • 813-745-1363

    Locations:

    • Mount Sinai Medical Center Miami
    • Miami Beach Florida 33140 United States
    • H. Lee Moffitt Cancer Center and Research Institute
    • Tampa Florida 33612 United States

    View trial on ClinicalTrials.gov


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    Published October 9, 2017
  • A Phase 3, Randomized, Study of Neoadjuvant Chemotherapy Alone Versus Neoadjuvant Chemotherapy Plus Nivolumab or Nivolumab and BMS-986205, Followed by Continued Post- Surgery Therapy With Nivolumab or Nivolumab and BMS-986205 in Participants With Muscle-

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    A Phase 3, Randomized, Study of Neoadjuvant Chemotherapy Alone Versus Neoadjuvant Chemotherapy Plus Nivolumab or Nivolumab and BMS-986205, Followed by Continued Post- Surgery Therapy With Nivolumab or Nivolumab and BMS-986205 in Participants With Muscle- Invasive Bladder Cancer


    Condition: Bladder Cancer, Muscle-Invasive Bladder Cancer, BMS-986205

    Intervention:

    • Biological: Nivolumab
    • Drug: BMS-986205
    • Drug: Gemcitabine
    • Drug: Cisplatin
    • Drug: BMS-986205 Placebo

    Purpose: A study to evaluate nivolumab + chemotherapy or nivolumab/ BMS-986205 + chemotherapy followed by continued Immuno-Oncology therapy after radical cystectomy (RC) compared with neoadjuvant standard of care (SOC) chemotherapy alone in patients with muscle-invasive bladder cancer (MIBC)

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03661320

    Sponsor: Bristol-Myers Squibb

    Primary Outcome Measures:

    • Measure: Pathological Complete Response (pCR) rate, in all randomized participants
    • Time Frame: Approx. 39 months
    • Safety Issue:
    • Measure: Event-Free Survival (EFS), in all randomized participants
    • Time Frame: Approx. 57 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Overall Survival (OS) in all randomized participants
    • Time Frame: Approx. 76 months
    • Safety Issue:
    • Measure: Incidence of Adverse Events (AE) in all treated participants
    • Time Frame: Approx. 76 months
    • Safety Issue:
    • Measure: Incidence of Serious Adverse Events (SAE) in all treated participants
    • Time Frame: Approx. 76 months
    • Safety Issue:
    • Measure: Incidence of Laboratory abnormalities in all treated participants
    • Time Frame: Approx. 76 months
    • Safety Issue:
    • Measure: Incidence of death in all treated participants
    • Time Frame: Approx. 76 months
    • Safety Issue:
    • Measure: Pathological Complete Response (pCR) rate, in all randomized participants
    • Time Frame: Approx. 39 months
    • Safety Issue:
    • Measure: Event Free Survival (EFS), in all randomized participants
    • Time Frame: Approx. 57 months
    • Safety Issue:

    Estimated Enrollment: 1200

    Study Start Date: October 12, 2018

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Participants with MIBC, clinical stage T2-T4a, N0 (<10 mm on CT or MRI), M0, diagnosed at TURBT and confirmed by radiographic imaging. Variant histology is acceptable if there is a predominant urothelial component.
    • Participant must be deemed eligible for Radial Cystectomy (RC) by his/her oncologist and/or urologist, and must agree to undergo Radial Cystectomy (RC) after completion of neoadjuvant therapy.
    • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

    Exclusion Criteria:

    • Clinical evidence of positive LN (≥ 10 mm in short axis) or metastatic bladder cancer
    • Prior systemic therapy, radiation therapy, or surgery for bladder cancer other than TURBT or biopsies is also not permitted
    • Ineligible to receive cisplatin due to Grade 2 or higher peripheral neuropathy or audiometric hearing loss, or calculated (Cockcroft-Gault formula) GFR or measured (24-hour urine) creatinine clearance (CrCl) < 50 mL/min

    Contact:

    • Recruiting sites have contact information. Please contact the sites directly. If there is no contact information
    • please email:

    Locations:

    • Local Institution
    • Mobile Alabama 36608 United States
    • Local Institution
    • Chandler Arizona 85224 United States
    • Arizona Oncology Associates
    • Tucson Arizona 85711 United States
    • Local Institution
    • Irvine California 92868 United States
    • Local Institution
    • La Jolla California 92093-0987 United States
    • UC Davis Comprehensive Cancer Center
    • Sacramento California 95817 United States
    • Local Institution
    • San Jose California 95124 United States
    • Rocky Mountain Cancer Centers Llp
    • Littleton Colorado 80120-4413 United States
    • Local Institution
    • New Haven Connecticut 06520 United States
    • Local Institution
    • Newark Delaware 19713 United States
    • Woodlands Medical Specialists, Pa
    • Pensacola Florida 32503 United States
    • H. Lee Moffitt Cancer Center
    • Tampa Florida 33612 United States
    • Northside Hospital
    • Atlanta Georgia 30342 United States
    • The University Of Chicago
    • Chicago Illinois 60637 United States
    • Illinois Cancer Care
    • Peoria Illinois 61615 United States
    • Local Institution
    • Baltimore Maryland 21201 United States
    • Maryland Oncology Hematology, P.A.
    • Columbia Maryland 21044 United States
    • Beth Israel Deaconess Medical Center
    • Boston Massachusetts 02215 United States
    • Dana Farber Cancer Institute
    • Boston Massachusetts 02215 United States
    • Minnesota Oncology Hematology
    • Minneapolis Minnesota 55404 United States
    • University of Minnesota
    • Minneapolis Minnesota 55455 United States
    • The Nebraska Medical Center
    • Omaha Nebraska 68198-6840 United States
    • Oncology Hematology West P.C. dba Nebraska Cancer Specialists
    • Omaha Nebraska 68310 United States
    • Comprehensive Cancer Centers Of Nevada
    • Las Vegas Nevada 89169 United States
    • Local Institution
    • Camden New Jersey 08103 United States
    • New York Oncology Hematology, Pc
    • Albany New York 12208 United States
    • Local Institution
    • Lake Success New York 11042 United States
    • Columbia University Medical Center (Cumc)
    • New York New York 10032 United States
    • Local Institution
    • Cleveland Ohio 44195 United States
    • Northwest Cancer Specialists, Pc
    • Tualatin Oregon 97062 United States
    • Local Institution
    • Charleston South Carolina 29425 United States
    • Vanderbilt University Medical Center
    • Nashville Tennessee 37232 United States
    • Texas Oncology, PA - Central Austin Cancer Center
    • Austin Texas 78731 United States
    • Local Institution
    • Dallas Texas 75390 United States
    • Local Institution
    • Fort Sam Houston Texas 78234 United States
    • Virginia Oncology Associates
    • Norfolk Virginia 23502 United States
    • Instituto Medico Especializado Alexander Fleming
    • Capital Federal Buenos Aires 1426 Argentina
    • Hospital Aleman
    • Ciudad Autonoma Buenos Aires Buenos Aires 1118 Argentina
    • Hospital Britanico De Buenos Aires
    • Ciudad Autonoma de Buenos Aires Buenos Aires 1280 Argentina
    • Local Institution
    • Garran Australian Capital Territory 2605 Australia
    • Local Institution
    • Kingswood New South Wales 2747 Australia
    • Local Institution
    • Macquarie Park New South Wales 2109 Australia
    • Local Institution
    • St Leonards New South Wales 2065 Australia
    • Calvary Hospital
    • North Adelaide South Australia 5006 Australia
    • Local Institution
    • Heidelberg Victoria 3084 Australia
    • Local Institution
    • Murdoch 6150 Australia
    • Local Institution
    • Klagenfurt Am Woerthersee 9020 Austria
    • Universitaetsklinikum Krems
    • Krems 3500 Austria
    • Krankenhaus der Elisabethinen Linz GmbH
    • Linz 4010 Austria
    • AKH Allgemeines Krankenhaus Wien
    • Wien 1090 Austria
    • Local Institution
    • Bruxelles 1200 Belgium
    • Local Institution
    • Gent 9000 Belgium
    • Local Institution
    • Leuven B-300 Belgium
    • Local Institution
    • Wilrijk 2610 Belgium
    • Local Institution
    • Fortaleza Ceara 60130-241 Brazil
    • Local Institution
    • Ipatinga Minas Gerais 35160-158 Brazil
    • Local Institution
    • Ijui RIO Grande DO SUL 98700-000 Brazil
    • Local Institution
    • Porto Alegre RIO Grande DO SUL 90610-000 Brazil
    • Local Institution
    • Barretos SAO Paulo 14780-070 Brazil
    • Local Institution
    • Jau SAO Paulo 17210-080 Brazil
    • Local Institution
    • Sao Jose Do Rio Preto SAO Paulo 15090-000 Brazil
    • Local Institution
    • Rio De Janeiro 20231-050 Brazil
    • Local Institution
    • Sao Paulo 01246-000 Brazil
    • Local Institution
    • Abbotsford British Columbia V2S 0C2 Canada
    • Local Institution
    • Kelowna British Columbia V1Y 5L3 Canada
    • Local Institution
    • North York Ontario M2K 1E1 Canada
    • Local Institution
    • Chicoutimi Quebec G7H 5H6 Canada
    • Local Institution
    • Montreal Quebec H3T 1M5 Canada
    • Pontificia Universidad Catolica de Chile
    • Santiago Metropolitana 8330024 Chile
    • Hospital Clinico de la Universidad De Chile
    • Santiago Metropolitana 8380456 Chile
    • Fundacion Arturo Lopez Perez
    • Santiago Metropolitana Chile
    • Foscal Internacional
    • Bucaramanga 681004 Colombia
    • Oncomedica S.A.
    • Monteria 230003 Colombia
    • Local Institution
    • ?lborg 9000 Denmark
    • Local Institution
    • Arhus 8000 Denmark
    • Local Institution
    • Herlev 2730 Denmark
    • Local Institution
    • Helsinki 00290 Finland
    • Local Institution
    • Tampere 33521 Finland
    • Local Institution
    • Turku 20521 Finland
    • Local Institution
    • Besancon 25030 France
    • Local Institution
    • Bordeaux 33075 France
    • Local Institution
    • Marseille 13273 France
    • Local Institution
    • Nice 06189 France
    • Local Institution
    • Paris 75014 France
    • Local Institution
    • Pierre Benite 69310 France
    • Local Institution
    • Rennes Cedex 35042 France
    • Local Institution
    • Saint Herblain Cedex 44805 France
    • Local Institution
    • Strasbourg Cedex 67091 France
    • Local Institution
    • TOULOUSE Cedex 9 31059 France
    • Universitaetsklinikum Aachen
    • Aachen 52074 Germany
    • Local Institution
    • Erfurt 99028 Germany
    • Klinik Essen-Mitte
    • Essen 45136 Germany
    • Johann Wolfgang Goethe Universitaet
    • Frankfurt Main 60590 Germany
    • Universitaetsmedizin Goettingen
    • Goettingen 37075 Germany
    • Local Institution
    • Heidelberg 69120 Germany
    • Marien Hospital Herne
    • Herne 44625 Germany
    • Universitaetsklinikum Jena
    • Jena 07747 Germany
    • University Hospital Schleswig-Holstein
    • Luebeck 23538 Germany
    • Universitaetsklinikum Magdeburg
    • Magdeburg 39120 Germany
    • Universitaetsmedizin Der Johannes Gutenberg-Universitaet
    • Mainz 55101 Germany
    • Klinikum rechts der Isar der TU
    • Muenchen 81675 Germany
    • Klinikum Nuernberg Nord, Urologische Klinik
    • Nuernberg 90419 Germany
    • Krankenhaus der Barmherzigen Brueder
    • Trier 54292 Germany
    • Local Institution
    • Athens 11528 Greece
    • Local Institution
    • Chaidari 12462 Greece
    • Local Institution
    • Larissa 41110 Greece
    • Local Institution
    • Beer Sheva 84101 Israel
    • Local Institution
    • Haifa 3109601 Israel
    • Local Institution
    • Ramat Gan 52621 Israel
    • Local Institution
    • Bari 70124 Italy
    • IRCCS Istituto Nazionale Tumori Milano
    • Milano 20133 Italy
    • Ospedale Di Carpi
    • Modena 41012 Italy
    • Istituto Oncologico Veneto IOV
    • Padova 35128 Italy
    • Azienda Ospedaliera Universitaria Pisana
    • Pisa 56126 Italy
    • Fondazione Policlinico Universitario A. Gemelli
    • Roma 00168 Italy
    • Local Institution
    • Komaki-shi Aichi 485-8520 Japan
    • Local Institution
    • Fukuoka-shi Fukuoka 8128582 Japan
    • Local Institution
    • Sapporo-shi Hokkaido 0030804 Japan
    • Local Institution
    • Sapporo Hokkaido 060-8543 Japan
    • Local Institution
    • Sapporo Hokkaido 0608604 Japan
    • Local Institution
    • Tsukuba-shi Ibaraki 3058576 Japan
    • Local Institution
    • Yokohama-shi Kanagawa 2220036 Japan
    • Local Institution
    • Niigata-shi Niigata 9518520 Japan
    • Local Institution
    • Osaka-sayama-shi Osaka 5898511 Japan
    • Local Institution
    • Takatsuki-shi Osaka 5698686 Japan
    • Local Institution
    • Hidaka-shi Saitama 3501298 Japan
    • Local Institution
    • Hamamatsu-shi Shizuoka 4313192 Japan
    • Local Institution
    • Minato-ku Tokyo 1058470 Japan
    • Local Institution
    • Shinjuku-Ku Tokyo 1608582 Japan
    • Local Institution
    • Kita-gun 7610793 Japan
    • Local Institution
    • Kyoto 606-8507 Japan
    • Local Institution
    • Goyang-si Gyeonggi-do 10408 Korea, Republic of
    • Local Institution
    • Seoul 02841 Korea, Republic of
    • Local Institution
    • Seoul 03080 Korea, Republic of
    • Local Institution
    • Seoul 06351 Korea, Republic of
    • Local Institution
    • La Paz BAJA Californa SUR 23040 Mexico
    • Local Institution
    • Df Distrito Federal 06720 Mexico
    • Local Institution
    • Zapopan Jalisco 45050 Mexico
    • Local Institution
    • Monterrey Nuevo LEON 64460 Mexico
    • Local Institution
    • Colima 28017 Mexico
    • Local Institution
    • Amsterdam 1066 CX Netherlands
    • Local Institution
    • Groningen 9713 GZ Netherlands
    • Local Institution
    • Sittard-Geleen 6162 BG Netherlands
    • Local Institution
    • Auckland 1023 New Zealand
    • Local Institution
    • Christchurch 8011 New Zealand
    • Local Institution
    • Gralum 1714 Norway
    • Local Institution
    • Lorenskog 1478 Norway
    • Local Institution
    • Oslo 0379 Norway
    • Local Institution
    • Lisboa 1649-035 Portugal
    • Local Institution
    • Porto 4200-072 Portugal
    • Institute Of Oncology "Prof.Dr.Alexandru Trestioreanu" Bucha
    • Bucharest 020122 Romania
    • Local Institution
    • Craiova 200347 Romania
    • Local Institution
    • Saint-Petersburg 194044 Russian Federation
    • Local Institution
    • St Petersburg 197758 Russian Federation
    • Local Institution
    • Singapore 169610 Singapore
    • Local Institution
    • Lugo 27003 Spain
    • Local Institution
    • Madrid 28007 Spain
    • Local Institution
    • Madrid 28033 Spain
    • Local Institution
    • Madrid 28041 Spain
    • Local Institution
    • Malaga 29010 Spain
    • Local Institution
    • Sevilla 41013 Spain
    • Local Institution
    • Kaohsiung 883 Taiwan
    • Local Institution
    • Taichung 40705 Taiwan
    • Local Institution
    • Taipei 10048 Taiwan
    • Local Institution
    • Taipei 11217 Taiwan
    • Local Institution
    • Chelmsford Essex CM1 7ET United Kingdom
    • Local Institution
    • York Yorkshire YO31 8HE United Kingdom
    • Local Institution
    • Glasgow G12 0YN United Kingdom
    • Local Institution
    • Lancaster LA1 4RP United Kingdom
    • Local Institution
    • London SE1 9RT United Kingdom
    • Local Institution
    • Oxford OX3 7LE United Kingdom

    View trial on ClinicalTrials.gov


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    Published June 4, 2019
  • A Phase I Single-Arm Study of the Combination of Durvalumab (MEDI4736) and Vicinium (Oportuzumab Monatox, VB4-845) in Subjects With High-Grade Non-Muscle-Invasive Bladder Cancer Previously Treated With BCG

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    A Phase I Single-Arm Study of the Combination of Durvalumab (MEDI4736) and Vicinium (Oportuzumab Monatox, VB4-845) in Subjects With High-Grade Non-Muscle-Invasive Bladder Cancer Previously Treated With BCG


    Condition: Urinary Bladder Neoplasms

    Intervention:

    • Drug: Durvalumab
    • Drug: Vicinium

    Purpose: Background: Non-muscle-invasive bladder cancer is in the early stages. But it usually comes back after treatment. The drugs Vicinium and Durvalumab may help the immune system find and destroy cancer cells. Objective: To test if the drugs Durvalumab and Vicinium together are safe and effective to treat people with bladder cancer that has not spread to the muscle in the bladder. Eligibility: People ages 18 and older who have bladder cancer that has not spread to the muscle in the bladder and was treated unsuccessfully with Bacillus Calmette-Guerin Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Tumor sample from previous surgery. If one is not available, they will have a biopsy: A small piece of tumor is removed. Cystoscopy to examine the inside of the bladder. This may include a biopsy or removing tumors. CT or MRI: They lie in a machine that takes pictures of the body. Electrocardiogram to test heart function Participants will receive Durvalumab and Vicinium in 2 phases: First phase: Durvalumab every 4 weeks and Vicinium once a week for 3 months Second phase: Durvalumab every 4 weeks and Vicinium once every other week Participants will have tumor samples taken every 3 months. They will have blood and urine tests throughout the study. Participants will continue treatment for up to 2 years. Participants will have a visit about 30 days after their last treatment. This includes blood and urine tests. It may include a cytoscopy or additional biopsies.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03258593

    Sponsor: National Cancer Institute (NCI)

    Primary Outcome Measures:

    • Measure: safety and tolerability
    • Time Frame: one year
    • Safety Issue:

    Estimated Enrollment: 40

    Study Start Date: June 7, 2018

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum 100 Years
    • Gender: All

    Inclusion Criteria:

    • Patients must have histologically or cytologically confirmed by NCI Laboratory of Pathology as high grade non-muscle invasive urothelial (transitional cell carcinoma) of the bladder as follows:
    • Carcinoma-in-situ (CIS) with or without papillary tumors
    • High-grade Ta or T1 disease based on a biopsy/TURBT performed within 12 weeks of the initial dose of study treatment. If multiple bladder biopsies/TURBTs are required to confirm eligibility, the timing of the last bladder biopsy to the initial dose of study treatment must be within 12 weeks.
    • Patients with persistent T1 high grade disease on TURBT following a single induction course of BCG (at least 5 of 6 doses) may also be eligible for this trial provided that the patient is surgically unfit for cystectomy as deemed by the investigator or the patient declines cystectomy.
    • Subjects with BCG unresponsive disease as defined by the Society of Urologic Oncology and the FDA: Subjects must have received at least two courses of intravesical BCG (at least 5 of 6 induction doses of BCG and at least 2 of 3 maintenance doses of BCG under a maintenance regimen or at least 2 doses of a repeat induction course). Please note exception above for persistent T1 disease. There is no upper limit on the amount of prior BCG a subject may have received.
    • Patients who have met eligibility criterion above must have received last BCG dose within a year of enrollment.
    • The investigator must document that he/she believes the subject would not benefit from additional BCG treatment at the time of study entry.
    • Age >= 18 years at time of signing the informed consent form (ICF). Because no dosing or adverse event data are currently available on the use of Vicinium in combination with durvalumab in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials. Furthermore, NMIBC does not occur in children.
    • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
    • Adequate organ and marrow function as defined below:
    • Hemoglobin >= 9.0 g/dL
    • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (> 1500 per mm^3)
    • Platelet count >= 75 x 10^9/L (>75,000 per mm^3)
    • Serum bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN).
    • AST (SGOT)/ALT (SGPT) less than or equal to 2.5 x institutional ULN
    • Creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
    • Males: Creatinine CL (mL/min) = (Weight (kg) x (140
    • Age))/72 x serum creatinine (mg/dL)
    • Females: Creatinine CL (mL/min)= (Weight (kg) x (140
    • Age) x 0.85 )/72 x serum creatinine (mg/dL)
    • Female subjects must either be of non-reproductive potential (i.e., post-menopausal as described below) OR history of surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
    • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
    • Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, or had chemotherapy-induced menopause with last menses >1 year ago
    • The effects of Vicinium and durvalumab on the developing human fetus are unknown. For this reason, all sexually active subjects agree to use barrier contraception (i.e., condoms) while receiving study treatment and for 120 days following their last dose of study treatment. Female subjects of child-bearing potential and male subjects whose sexual partners are WOCBP agree to use barrier contraception and a second form of contraception while receiving study treatment and for 4 months following their last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
    • Written informed consent obtained from the subject prior to performing any protocol- related procedures
    • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
    • Body weight > 30 kg

    Exclusion Criteria:

    • Patients who are receiving any other investigational agents.
    • QT interval corrected for heart rate using Fridericia s formula (QTcF) >=470 ms. (Any clinically significant abnormalities detected require triplicate ECG results and a mean QT interval corrected for heart rate using Fridericia s formula (QTcF) >=470 ms calculated from 3 ECGs.)
    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Vicinium or durvalumab or other agents used in the study.
    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Urinary tract infections (UTIs) are excluded from being an exclusion criterion for treatment unless they are grade 3 or higher.
    • Pregnant women are excluded from this study because it is unknown whether Vicinium and/or durvalumab have any teratogenic effects. In nursing mothers, breastfeeding should be discontinued as these medications may have the potential risk for adverse events in nursing infants secondary to treatment of the mother.
    • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
    • Evidence of non-bladder urothelial (transitional cell) carcinoma by biopsy, cytology, or radiological imaging within the past 2 years of treatment (e.g. upper tract transitional cell carcinoma, urethral urothelial carcinoma).
    • Subjects with hydronephrosis, except for those subjects where hydronephrosis has been longstanding (i.e., predates the diagnosis of the CIS, Ta, or T1 by more than 2 years) and diagnostic evaluation at screening shows no evidence of tumor causing the hydronephrosis.
    • Any other anticancer therapy (e.g., chemotherapy, biologic therapy, immunotherapy, targeted therapy, endocrine therapy, radiation therapy, intravesical therapy, investigational agent) within 28 days of the first dose of study therapy (and within 6 weeks for nitrosourea or mitomycin C) other than a single dose of intravesical chemotherapy which is permitted between 28 days and 14 days prior to the first dose of study treatment.
    • The subject has a diagnosis of another malignancy within 2 years before the first dose of study treatment, except for superficial skin cancer, localized prostate cancer on active surveillance, or localized solid tumors deemed cured by surgery and not treated with systemic anticancer therapy and not expected to require anticancer therapy in the next 2 years i.e., while the subject may be taking study treatment.
    • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
    • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g. colitis or Crohn s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
    • Subjects with vitiligo or alopecia
    • Subjects with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormonal replacement
    • Any chronic skin condition that does not require systemic therapy
    • Subjects without active disease in the last 5 years may be included but only after consultation with the Principal Investigator
    • Subjects with celiac disease controlled by diet alone
    • History of primary immunodeficiency.
    • History of allogeneic organ transplant.
    • History of hypersensitivity to durvalumab or any excipient
    • History of hypersensitivity to Vicinium or its components
    • Active infection with tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and PPD testing if indicated), hepatitis B (known positive HBV surface antigen (HBsAg) result, hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with HIV are excluded from participating on this clinical trial because their immunodeficiency would confound the evaluation of adverse events which would hinder meeting the primary objective. Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
    • History of leptomeningeal carcinomatosis
    • Receipt of live attenuated vaccination within 30 days prior to the first dose of Vicinium or durvalumab
    • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
    • Subjects with uncontrolled seizures
    • Any unresolved toxicity NCI CTCAE Grade >=2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
    • Subjects with Grade >=2 neuropathy will be evaluated on a case-by-case basis after consultation with the Principal Investigator.
    • Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Principal Investigator.

    Contact:

    • Sonia E Bellfield, R.N.
    • (240) 760-6118

    Location:

    • National Institutes of Health Clinical Center
    • Bethesda Maryland 20892 United States

    View trial on ClinicalTrials.gov


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    Published July 5, 2018
  • A Phase II Open Label Single Arm Study of Adjuvant Nivolumab Following Chemo-Radiation in Localized Muscle-Invasive Bladder Cancer (NEXT)

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    A Phase II Open Label Single Arm Study of Adjuvant Nivolumab Following Chemo-Radiation in Localized Muscle-Invasive Bladder Cancer (NEXT)


    Condition: Bladder Cancer

    Intervention:

    • Drug: Nivolumab

    Purpose: This is a phase 2, single arm, open label trial to evaluate the rate of failure free survival at 2 years after start of chemoradiation with adjuvant nivolumab in adult subjects who undergo chemoradiation for localized bladder cancer.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03171025

    Sponsor: University of Utah

    Primary Outcome Measures:

    • Measure: Two-year rate of failure-free survival (FFS)
    • Time Frame: 2 years
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Rate of failure-free survival at two years in subjects with intact bladder (FFSIB).
    • Time Frame: 2 years
    • Safety Issue:
    • Measure: Rate of acute and late grade 2 or higher treatment related Genitourinary, Gastrointestinal, hematologic and immune related adverse events.
    • Time Frame: Patient safety will be evaluated throughout the treatment period and follow up (treatment with Nivolumab is expected to last 1 year for each patient and follow up for 2 years)
    • Safety Issue:
    • Measure: Effect of treatment on Quality of Life
    • Time Frame: Quality of life questionnaires done every 3 months while patients are on treatment for 1 year
    • Safety Issue:
    • Measure: Cystoscopic Local Control
    • Time Frame: Done at 6 months, 1 year and 2 years
    • Safety Issue:
    • Measure: Rate of salvage cystectomy
    • Time Frame: During study treatment that is expected to last for 1 year
    • Safety Issue:
    • Measure: Rate of distant failure free survival
    • Time Frame: 2 years
    • Safety Issue:
    • Measure: Overall Survival
    • Time Frame: 5 years
    • Safety Issue:

    Estimated Enrollment: 28

    Study Start Date: July 10, 2017

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Patients with muscularis propria invasion clinical stages 2 to 4 (T2-4a, N0 or N+, M0 or T1 with N+), who are not candidates for radical cystectomy.
    • Patients may have undergone partial cystectomy for removal of bladder tumor prior to chemoradiation.
    • Staging is determined prior to chemoradiation
    • Patients have been evaluated by a urologic oncologist to determine eligibility for radical cystectomy prior to chemoradiation. Patients may not be candidates for radical cystectomy due to one or more reasons such as but not limited to comorbidities, age, surgical risk or patient refusal to undergo radical cystectomy. Patients who refuse to undergo radical cystectomy are not required to be evaluated by a urologic oncologist.
    • Patients must have histologically proven primary carcinoma of the bladder or urethra or lower ureter (adenocarcinoma or transitional or squamous-cell carcinoma)
    • Treating investigator has determined that the patients are not a candidate for radical cystectomy. Patients have been evaluated by a urologic oncologist to determine eligibility for radical cystectomy prior to chemoradiation. Patients may not be candidates for radical cystectomy due to one or more reasons such as, but not limited to, comorbidities, age, surgical risk, or patient refusal to undergo radical cystectomy.
    • Tumor tissue from the most recently resected site of disease (preferable) or from the transurethral resection that yielded the initial muscle invasive diagnosis must be provided for biomarker correlative analyses. Enrollment is permitted if adequate archived tissue is unavailable.
    • Patients must have received systemic radiosensitizing chemotherapy with definitive pelvic radiation therapy. Patients may have received partial amount of chemotherapy and radiation (both) to be eligible.
    • Platinum based chemotherapy prior to chemoradiation is permitted but not mandatory
    • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2
    • Age ≥18.
    • Adequate bone marrow function White Blood Cell (WBC) > 2000/µl, neutrophils >1500/µl, Hemoglobin >9.0 g/dl.
    • Serum bilirubin and aminotransferase values less than 1.5 times the upper limit of the normal range
    • Creatinine clearance of 20 ml/min or greater as measured by the Cockroft-Gault formula
    • Able to start study treatment within 90 days of completion of chemoradiation.
    • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
    • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
    • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.
    • All toxicities attributed to prior anti-cancer therapy other than nephropathy, neuropathy, hearing loss, alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 4.03) or baseline before administration of study drug. Subjects with toxicities attributed to prior anti-cancer therapy which are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum based therapy, are permitted to enroll.
    • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

    Exclusion Criteria:

    • Evidence of distant metastases or lymph node metastasis (es) that was not within the radiation field.
    • Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin. A history of localized early stage malignancy that has undergone potentially curative therapy or is low grade and does not require active treatment is allowed.
    • Diffuse bladder carcinoma in situ (CIS) that was not able to be encompassed in a boost radiotherapy volume
    • Patients with inflammatory bowel disease
    • Patients with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
    • Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration. Inhaled, ocular, intraarticular, intranasal and topical steroids are permitted.
    • Patients with a known chronic immunocompromised state, HIV infection or active Hepatitis B or Hepatitis C infection.
    • Pregnancy or women of childbearing potential not willing to use contraception and men who are sexually active and not willing/able to use medically acceptable forms of contraception and breast-feeding women not willing to stop breastfeeding during study.
    • Severe active co-morbidity as determined by the investigator or principal investigator
    • Life expectancy less than 2 years

    Contact:

    • Hillary Finch
    • 801-213-6126

    Location:

    • Huntsman Cancer Institute
    • Salt Lake City Utah 84112 United States

    View trial on ClinicalTrials.gov


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    Published October 9, 2017
  • A Phase II Study Investigating Preoperative MPDL3280A in Operable Transitional Cell Carcinoma of the Bladder (ABACUS)

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    A Phase II Study Investigating Preoperative MPDL3280A in Operable Transitional Cell Carcinoma of the Bladder (ABACUS)


    Condition: Bladder Cancer

    Intervention:

    • Drug: MPDL3280A

    Purpose: ABACUS is an open-label, international, multi-centre, window of opportunity phase II trial for patients with histologically confirmed (T2-T4a) transitional cell carcinoma of the bladder. The trial aims to test the efficacy of preoperative MPDL3280A and will include extensive biomarker work on samples from these patients. Eligible patients will receive two 3-weekly cycles of MPDL3280A pre-cystectomy. Following cystectomy, patients will be followed up for safety, survival, and disease data.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02662309

    Sponsor: Queen Mary University of London

    Primary Outcome Measures:

    • Measure: Efficacy of MPDL3280A pre-cystectomy with respect to pathological complete response rate (pCRR)
    • Time Frame: 2-3 months (timeframe dependent on delay to surgery)
    • Safety Issue:
    • Measure: Efficacy of MPDL3280A pre-cystectomy on immune parameters
    • Time Frame: 2-3 months (timeframe dependent on delay to surgery)
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Safety and tolerability of MPDL3280A when given to this patient population pre-cystectomy
    • Time Frame: Approx 34 weeks (from screening registration, throughout treatment and up to 24 weeks post-cystectomy - timeframe dependent on delay to surgery)
    • Safety Issue:
    • Measure: Efficacy of MPDL3280A pre-cystectomy with respect to anti-tumour effects as measured by radiological response (RR)
    • Time Frame: Approx 34 weeks (timeframe dependent on delay to pre-cystectomy visit)
    • Safety Issue:
    • Measure: Efficacy of MPDL3280A pre-cystectomy with respect to anti-tumour effects based on disease free survival (DFS)
    • Time Frame: Up to 2 years post-cystectomy
    • Safety Issue:
    • Measure: Efficacy of MPDL3280A pre-cystectomy with respect to anti-tumour effects based on overall survival (OS)
    • Time Frame: Up to 2 years post-cystectomy
    • Safety Issue:

    Estimated Enrollment: 85

    Study Start Date: February 2016

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • 1. Willing and able to provide written informed consent 2. Ability to comply with the protocol 3. Age ≥ 18 years 4. Histopathologically confirmed transitional cell carcinoma (T2-T4a) of the bladder. Patients with mixed histologies are required to have a dominant transitional cell pattern. 5. Residual disease after TURBT (surgical opinion, cystoscopy or radiological presence). 6. Fit and planned for cystectomy (according to local guidelines). 7. N0 or M0 disease CT or MRI (within 4 weeks of registration) 8. Representative formalin-fixed paraffin embedded (FFPE) bladder tumour samples with an associated pathology report that are determined to be available and sufficient for central testing. 9. Patients who refuse neoadjuvant cisplatin based chemotherapy or in whom neoadjuvant cisplatin based therapy is not appropriate. 10. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 11. Negative pregnancy test within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential. 12. For female patients of childbearing potential to use a highly effecting form(s) of contraception (i.e. one that results in a low failure rate [<1% per year] when used consistently and correctly) and to continue its use for 90 days after the last dose of MPDL3280A. 13. Adequate hematologic and end-organ function within 4 weeks prior to the first study treatment defined by the following:
    • ANC ≥ 1500 cells/μL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
    • WBC counts > 2500/μL
    • Lymphocyte count ≥ 500/μL
    • Platelet count ≥ 100,000/μL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
    • Haemoglobin ≥ 9.0 g/dL (patients may be transfused or receive erythropoietic treatment to meet this criterion).
    • AST or ALT, and alkaline phosphatase ≤ 2.5 times the institutional upper limit of normal (ULN) (patients with known Gilbert disease who have serum bilirubin level ≤ 3 × the institutional ULN may be enrolled).
    • INR and aPTT ≤ 1.5 × the institutional ULN. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
    • Calculated creatinine clearance ≥ 20 mL/min (Cockcroft-Gault formula)

    Exclusion Criteria:

    1. Pregnant and lactating female patients.
    2. Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
    3. Previously intravenous chemotherapy for bladder cancer.
    4. Patients with prior allogeneic stem cell or solid organ transplantation.
    5. Prior treatment with CD137 agonists, anti-CTLA-4, anti−programmed death−1 (PD-1), or anti−PD-L1 therapeutic antibody or pathway-targeting agents.
    6. Patients must not have had oral or IV steroids for 14 days prior to study entry. The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids (i.e., for adrenal insufficiency), and mineralocorticoids (e.g., fludrocortisone) is allowed.
    7. Received therapeutic oral or intravenous (IV) antibiotics within 14 days prior to enrolment (Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible).
    8. Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study.
    9. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]−2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.
    10. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to enrolment.
    11. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).
    12. Malignancies other than UBC within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score ≤ 3 + 4 and PSA < 10 ng/mL undergoing active surveillance and treatment naive).
    13. Severe infections within 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
    14. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina.
    15. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan (History of radiation pneumonitis in the radiation field (fibrosis) is permitted).
    16. Patients with uncontrolled Type 1 diabetes mellitus. Patients with Type 1 diabetes controlled on a stable insulin regimen are eligible.
    17. Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
    18. Positive test for HIV
    19. Patients with active tuberculosis
    20. History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
    21. Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > the institutional ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while on study.
    22. History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
    23. Patients with a history of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone.
    24. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    25. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the MPDL3280A formulation

    Contact:

    • ABACUS Coordinator
    • 020 7882 8275

    Locations:

    • Centre Hospitalier Universitaire (CHU) de Bordeaux
    • Bordeaux France
    • Hospices Civils de Lyon
    • Lyon France
    • Institut Paoli-Calmettes
    • Marseille France
    • Institut Claudius Régaud
    • Toulouse France
    • Universitätsklinik Köln
    • Cologne Germany
    • Universitätsklinikum Düsseldorf
    • Düsseldorf Germany
    • Universitätsklinikum des Saarlandes
    • Homburg Germany
    • Universitätsklinikum Schleswig-Holstein
    • Lübeck Germany
    • LMU: Urologische Klinik und Poliklinik
    • Munich Germany
    • Universitätsklinikum Tübingen
    • Tübingen Germany
    • Netherlands Cancer Institute (NKI)
    • Amsterdam Netherlands
    • Athaia Xarxa Manresa
    • Barcelona Spain
    • Hospital del Mar
    • Barcelona Spain
    • Hospital Germans Trias i Pujol
    • Barcelona Spain
    • Hospital Santa Creu i Sant Pau
    • Barcelona Spain
    • Hospital Vall d'Hebron
    • Barcelona Spain
    • Hospital Reina Sofía
    • Córdoba Spain
    • Hospital 12 de Octubre
    • Madrid Spain
    • CHU de Santiago
    • Santiago de Compostela Spain
    • Hospital Virgen del Rocío
    • Sevilla Spain
    • Cambridge University Hospitals NHS Trust
    • Cambridge United Kingdom
    • Clatterbridge Cancer Centre NHS Foundation Trust
    • Liverpool United Kingdom
    • Barts Health NHS Trust
    • London United Kingdom
    • University College London Hospitals NHS Foundation Trust
    • London United Kingdom
    • Oxford University Hospitals NHS Foundation Trust
    • Oxford United Kingdom
    • Sheffield Teaching Hospitals NHS Foundation Trust
    • Sheffield United Kingdom
    • University Hospital Southampton NHS Foundation Trust
    • Southampton United Kingdom

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • A Phase II Study of Chemoradiation for Bladder Preservation in Patients With Muscle Invasive Bladder Carcinoma After Complete Response to Neoadjuvant Chemotherapy

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    A Phase II Study of Chemoradiation for Bladder Preservation in Patients With Muscle Invasive Bladder Carcinoma After Complete Response to Neoadjuvant Chemotherapy


    Condition: Bladder Cancer, Bladder Carcinoma, Transition Cell Cancer, Muscle Invasive Bladder Carcinoma

    Intervention:

    • Procedure: Transurethral Resection of the Bladder Tumor & Cystoscopy
    • Radiation: Intensity Modulated Radiation Therapy
    • Behavioral: Expanded Prostate Cancer Index Composite Short Form 12
    • Behavioral: International Prostate Symptom Score

    Purpose: Bladder preservation in patients with complete response after neoadjuvant chemotherapy will lead to equivalent or superior relapse free rates compared to cystectomy rates from historical controls.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02145390

    Sponsor: University of Miami

    Primary Outcome Measures:

    • Measure: Rate of Failure-Free Survival with Intact Bladder (FFSIB) in Study Participants
    • Time Frame: 2 years
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Rate of Failure-Free Survival (FFS) at two years
    • Time Frame: 2 Years
    • Safety Issue:
    • Measure: Rate of Acute and Late Grade 2 or Higher Treatment-Related GU, GI and Hematologic Toxicity.
    • Time Frame: Up to 2 years Post-Treatment
    • Safety Issue:
    • Measure: Rate of Overall Survival in Study Participants
    • Time Frame: Up to 3 years
    • Safety Issue:

    Estimated Enrollment: 68

    Study Start Date: January 5, 2016

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • 1. Pathologically proven diagnosis of primary carcinoma of the bladder(transitional cell cancer). Must be operable patients with muscularis propria invasion and American Joint Committee on Cancer (AJCC) clinical stages T2-4a, N0 or N+, M0. Patients with prostatic urethra involvement with transitional cell cancer (TCC) are eligible if it is completely resected and the patient has no evidence of stromal invasion of the prostate. 2. Patients must be able to tolerate systemic chemotherapy combined with pelvic radiation therapy and radical cystectomy. 3. Zubrod Performance Status of ≤1. 4. Age ≥18. 5. Complete Blood Count (CBC)/differential obtained no more than 8 weeks prior to enrollment on study, with adequate bone marrow function defined as follows:
    • White Blood Cell (WBC) ≥ 4000/ml
    • Absolute neutrophil count (ANC) ≥1,800 cells/mm
    • Platelets ≥100,000 cells/mm
    • Hemoglobin ≥ 10.0 mg/dl (Note: the use of transfusion or other intervention to achieve this level is acceptable) 6. Serum bilirubin of 2.0mg or less; 7. Serum creatinine of 1.5mg or less; creatinine clearance of 60ml/min or greater no more than 8 weeks prior to enrollment (Note: calculated creatinine clearance is permissible, using Cockcroft-Gault formula. If the creatinine clearance is greater than 60ml/min, then a serum creatinine of up to 1.8mg is allowable at the discretion of the principal investigator.) Note: Prechemotherapy laboratory investigations and Eastern Cooperative Oncology Group (ECOG) evaluation must meet inclusion criteria irrespective of where they were drawn, retroactive, prior to cycle 1 of cisplatin/gemcitabine. Inclusion criteria from these initial investigations will be used for evaluation of enrollment eligibility. 8. Patients must be willing and able to provide study-specific informed consent prior to study entry

    Exclusion Criteria:

    • 1. Tumor related untreated active hydronephrosis 2. Evidence of distant metastases. 3. Diffuse bladder carcinoma in situ (CIS) not able to be encompassed in a boost radiotherapy volume. 4. Previous systemic chemotherapy (for any cancer) or pelvic radiation therapy 5. A prior or concurrent malignancy of any other site or histology unless the patient has been disease free for greater than or equal to five years except for non-melanoma skin cancer and/or stage T1a prostate cancer or carcinoma in situ of the uterine cervix 6. Patients that are not candidates for radical cystectomy (T4b disease are considered unresectable) 7. Pregnancy or women of childbearing potential [not post-menopausal or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy)] and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic 8. Severe active co-morbidity:
    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of enrollment
    • History of hepatic insufficiency resulting in clinical jaundice and/or coagulation defects (Note: laboratory tests for liver function and coagulation parameters are not required for enrollment into this protocol)
    • Known diagnosis of Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition (Note: HIV testing is not required for enrollment into this protocol). The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
    • As determined by the investigator or principal investigator

    Location:

    • University of Miami Sylvester Comprehensive Cancer Center
    • Miami Florida 33136 United States

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • A Phase II Study of the Anti-PD-L1 Antibody MPDL3280A in Subjects With Non-metastatic Transitional Cell Carcinoma of the Bladder

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    A Phase II Study of the Anti-PD-L1 Antibody MPDL3280A in Subjects With Non-metastatic Transitional Cell Carcinoma of the Bladder


    Condition: Carcinoma, Transitional Cell

    Intervention:

    • Drug: MPDL3280A Dose Level 1
    • Drug: MPDL3280A Dose Level 2
    • Drug: MPDL3280A Dose Level 3

    Purpose: This is a single arm, open label Phase II study of MPDL3280A, an anti-PD-L1 antibody administered as neoadjuvant therapy to subjects with either BCG-refractory non-muscle invasive transitional cell carcinoma (TCC) of the bladder, or muscle-invasive TCC appropriate for cystectomy and refusing or ineligible for neoadjuvant chemotherapy. Enrolled patients will be assigned sequentially to dose levels in cohorts of 6 patients per dose level. The starting dose level is 1200mg x 1 dose and will be escalated in subsequent cohorts to 1200mg q 3 weeks x 2 doses, and finally 1200mg q 3 weeks x 3 doses to determine the impact of increasing number of treatments on the modulated immune response with the tumor tissue. Subjects with adverse pathology (pT3/pT4 or N+) will be offered the option of adjuvant MPDL3280A for up to 16 cumulative cycles of treatment. After all neoadjuvant study therapy is administered, each subject will undergo cystectomy to evaluate pathologic response to treatment and for immunologic characterization in the resected tissue. Serum and urine will be obtained as well to characterize circulating immune responses. After the multi-dose portion of the study has completed accrual two expansion cohorts of up to 15 patients each with NMIBC or MIBC will be accrued at the highest dose level for further characterization of safety, efficacy, and immunologic analysis. Patients with pT3, pT4, or N+ disease at the time of cystectomy and no metastatic disease will be offered the option of adjuvant MPDL3280A for up to a total of 16 cumulative cycles. All subjects will be followed clinically for up to 2 years to assess for disease recurrence.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02451423

    Sponsor: University of California, San Francisco

    Primary Outcome Measures:

    • Measure: Change in CD3+ T cell count/µm2
    • Time Frame: Up to 1 year
    • Safety Issue:
    • Measure: Pathologic T0 rate
    • Time Frame: procedure
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Adverse Events
    • Time Frame: Up to 2 years
    • Safety Issue:
    • Measure: Percentage of treatment-related delay in surgery
    • Time Frame: Starting at Week 12
    • Safety Issue:
    • Measure: Frequency of treatment related Adverse Events
    • Time Frame: Up to 6 months
    • Safety Issue:
    • Measure: Frequency of treatment related Adverse Events
    • Time Frame: Up to 2 years
    • Safety Issue:

    Estimated Enrollment: 42

    Study Start Date: April 2016

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • 18 years of age or older
    • ECOG performance status 0, 1
    • Histologically document transitional cell carcinoma with the presence of any of the following stages: CIS, high-grade Ta, any grade T1, or any grade cT2-T4, considered appropriate for radical cystectomy. Subjects with mixed histology are required to have a dominant TCC pattern.
    • For subjects with NMIBC, BCG-refractory or BCG-resistant disease. BCG-refractory disease is defined as the absence of a complete response by 6 months in patients who have received induction and maintenance OR two induction courses of BCG. BCG-resistant disease is defined as persistent or recurrent disease after 2 induction courses of BCG within 1 year OR cancer recurrence within 1 year of initiation of therapy for patients who have received induction plus maintenance BCG therapy. Subjects with NMIBC must be suitable for and willing to undergo a radical cystectomy at the completion of study therapy.
    • For subjects with muscle invasive disease: not suitable neoadjuvant cisplatin-based chemotherapy as determined by the following:
    • Creatinine clearance less than 60ml/min. GFR should be assessed by calculation from serum/plasma creatinine (Cockcroft-Gault formula)
    • CTCAE Gr >/= 2 hearing loss
    • CTCAE Gr >/= 2 neuropathy
    • Subjects with MIBC not meeting the above criteria are still eligible provided the patient declines neoadjuvant cisplatin-based chemotherapy, after specific informed consent describing the known benefits of cisplatin-based chemotherapy. The reason for declining must be documented.
    • Adequate bone marrow function defined as
    • WBC > 2500 cells/mm3
    • ANC > 1500 cells/mm3
    • Hemoglobin > 9 g/dL. Patients may be transfused or receive erythropoietic treatment to meet this criterion.
    • Platelet count > 100,000 cells/mm3
    • Adequate renal function: Serum creatinine < 2 mg/dL OR calculated CrCl > 30ml/min
    • Serum bilirubin < 1.5 x ULN (except for patients with documented Gilbert's disease)
    • AST and ALT < 2.5 x ULN
    • Ability to understand and willingness to sign a written informed consent.
    • Have available evaluable archival tumor tissue for PD-L1 biomarker assessment. Presence of PD-L1 antigen on tumors is NOT required for study entry.
    • The effects of MPDL3280A on the developing human fetus are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception prior to study entry, during study participation, and for 90 days after study treatment discontinuation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 90 days after completion of study drug administration.

    Exclusion Criteria:

    • Subjects with primary TCC of the ureter, urethra, or renal pelvis without TCC of the bladder are not allowed.
    • Known distant metastatic disease (e.g. pulmonary or hepatic metastases).
    • Subjects with malignant lymphadenectomy in the abdomen or pelvis considered appropriate for radical cystectomy and lymphadnectomy with the goal of complete resection of all malignant disease are allowed.
    • Intravesical chemo- or biologic therapy within 6 weeks of first treatment.
    • Prior systemic chemotherapy or radiation therapy for transitional cell carcinoma of the bladder.
    • Subjects who have received prior intravesical chemotherapy are allowed.
    • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti CTLA-4, anti-PD1 and anti-PD-L1 therapeutic antibodies.
    • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vacuities, or glomerulonephritis.
    • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study.
    • Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen are eligible for this study.
    • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
    • History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
    • Chronic liver disease
    • HIV or active hepatitis B virus (HBV; chronic or acute; defined as having a positive hepatitis B surface antigen [Bag] test at screening) or active hepatitis C
    • Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBc Ab] and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1, but detection of HBV DNA in these patients will not exclude study participation.
    • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
    • Active tuberculosis
    • Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
    • Prior allogeneic stem cell or solid organ transplant
    • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study. Inactivated vaccines (such as hepatitis A or polio vaccines) are permitted during the study.
    • Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to Cycle 1, Day 1 and for at least 12 weeks after the last dose.
    • Clinically significant active infection or uncontrolled medical condition
    • Uncontrolled cystitis, significant bladder pain or spasms, or gross hematuria that in the opinion of the treating investigator, should preclude study entry.
    • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina
    • Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
    • Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure other than cystectomy during the course of the study
    • Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial
    • Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the Study Chair.
    • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone for adrenal insufficiency) is allowed.
    • Pregnant or nursing women are excluded
    • Known hypersensitivity to Chinese hamster ovary (CHO) cell products or any component of the MPDL3280A formulation
    • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    • Malignancies other than UC within 5 years prior to Cycle 1, Day 1, with the exception of those with a low risk of metastasis or death treated with expected curative outcome (such as, but not limited to, adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent and absence of PSA relapse, or ductal carcinoma in situ of the breast treated surgically with curative intent) or incidental prostate cancer (T1a, Gleason score ≤ 6 and PSA < 0.5 ng/mL).

    Contact:

    • Lawrence Fong, MD
    • 877-827-3222

    Location:

    • University of California, San Francisco
    • San Francisco California 94158 United States

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • A Phase II Trial of MK3475 in Combination With Gemcitabine and Concurrent Hypofractionated Radiation Therapy as Bladder Sparing Treatment for Muscle-Invasive Urothelial Cancer of the Bladder

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    A Phase II Trial of MK3475 in Combination With Gemcitabine and Concurrent Hypofractionated Radiation Therapy as Bladder Sparing Treatment for Muscle-Invasive Urothelial Cancer of the Bladder


    Condition: Muscle-invasive Urothelial Cancer of the Bladder

    Intervention:

    • Biological: Pembrolizumab
    • Procedure: Transurethral Resection of Bladder Tumor
    • Drug: Gemcitabine
    • Radiation: External Beam Radiation Therapy

    Purpose: This trial is to assess the efficacy of pembrolizumab (MK3475) added to concurrent radiation and gemcitabine in the management of patients with muscle-invasive urothelial cancer who are not candidates for or decline radical cystectomy.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02621151

    Sponsor: NYU Langone Health

    Primary Outcome Measures:

    • Measure: Two-year bladder-intact disease-free survival rate
    • Time Frame: 2 years
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Safety (adverse events) of the protocol therapy
    • Time Frame: From beginning of protocol therapy to 90 days after the end of radiation therapy
    • Safety Issue:
    • Measure: Complete response (CR) rate
    • Time Frame: up to 21 weeks
    • Safety Issue:
    • Measure: Overall survival
    • Time Frame: up to 5 years
    • Safety Issue:
    • Measure: Metastasis-free survival
    • Time Frame: up to 5 years
    • Safety Issue:

    Estimated Enrollment: 54

    Study Start Date: August 11, 2016

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologically confirmed muscle-invasive urothelial cancer of the bladder within 60 days of study enrollment. Patients must be willing to provide a TURBT specimen during screening and prior to enrollment if adequate specimen (FFPE tissue block or 20 unstained slides) from initial TURBT documenting muscle-invasive urothelial bladder cancer is not available.
    • Clinical stage T2-T4a, N0, M0 urothelial bladder cancer.
    • Deemed to not be a candidate for radical cystectomy by attending urologic oncologist or refuse radical cystectomy.
    • Be willing and able to provide written informed consent/assent for the trial.
    • Be ≥ 18 years of age on day of signing informed consent.
    • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance Scale.
    • Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of protocol enrollment.
    • Absolute neutrophil count >= 1,500 /mcL;
    • Platelets >= 100,000 /mcL;
    • Hemoglobin >= 9.0 g/dL;
    • Serum creatinine <=1.5 x upper limit of normal (ULN) or calculated creatinine clearance >= 30 mL/min as calculated by Cockcrof-Gault formaulae or by 24 hour urine collection;
    • Serum total bilirubin <=1.5 x ULN or direct bilirubin <= ULN for subjects with total bilirubin levels > 1.5 x ULN;
    • Aspartate aminotransferase and alanine aminotransferase <= 1.5 x ULN;
    • Albumin >= 2.5 mg/dL;
    • International normalized ratio or prothrombin time (PT) <= 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial prothrombin time (PTT) is within therapeutic range of intended use of anticoagulants;
    • Activated Partial Thromboplastin Time (aPTT) <= 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
    • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
    • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
    • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

    Exclusion Criteria:

    • Has received prior targeted small molecule therapy, radiation therapy or systemic chemotherapy for urothelial bladder cancer including neoadjuvant chemotherapy. Prior intravesical chemotherapy or intravesical immunotherapy is permissible, however, no prior intravesical therapy is permitted within 4 weeks of study enrollment; adjuvant therapy is not permitted.
    • Has received prior pelvic radiation therapy.
    • Has a history of inflammatory bowel disease or history of scleroderma.
    • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
    • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
    • Has a known history of active TB (Bacillus Tuberculosis).
    • Hypersensitivity to pembrolizumab or any of its excipients.
    • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
    • If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
    • Any prior history of invasive malignancy within the past 5 years except non-melanoma skin cancer, carcinoma in-situ, localized prostate cancer without biochemical recurrence following definitive treatment.
    • Has any history of inflammatory bowel disease or scleroderma.
    • Has other active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
    • History of Guillain-Barre Syndrome or Stevens-Johnson Syndrome
    • Has known history of, or any evidence of active, non-infectious pneumonitis.
    • Has an active infection requiring systemic therapy.
    • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
    • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
    • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
    • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
    • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
    • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
    • Has received a live vaccine within 30 days of planned start of study therapy. Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

    Contact:

    • Arjun Balar, MD
    • 212-731-5820

    Locations:

    • University of Chicago
    • Chicago Illinois 60637 United States
    • University of Michigan Health System
    • Ann Arbor Michigan 48109 United States
    • NYU Perlmutter Cancer Center
    • New York New York 10016 United States
    • Memorial Sloan Kettering
    • New York New York 10065 United States
    • University of North Carolina
    • Chapel Hill North Carolina 27599-7305 United States

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • A Phase III Multicentre Randomised Controlled Trial to Compare the Efficacy of Robotically Assisted Radical Cystectomy (RARC) and Intracorporeal Urinary Diversion With Open Radical Cystectomy (ORC) in Patients With Bladder Cancer

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    A Phase III Multicentre Randomised Controlled Trial to Compare the Efficacy of Robotically Assisted Radical Cystectomy (RARC) and Intracorporeal Urinary Diversion With Open Radical Cystectomy (ORC) in Patients With Bladder Cancer


    Condition: Bladder Cancer

    Intervention:

    • Procedure: Intracorporeal Robot Assisted Radical Cystectomy
    • Procedure: Open Radical Cystectomy

    Purpose: This is a prospective multicentre randomised controlled trial comparing the outcomes from Intracorporeal RARC (iRARC) with open radical cystectomy (ORC) in patients with bladder cancer. The study will recruit patients with non-muscle invasive bladder cancer (NMIBC) or muscle invasive bladder cancer (MIBC) who have selected radical cystectomy for the treatment of bladder cancer. The time of interest for measurement of the primary outcomes will be 90 days post-surgery. Eligible patients will include those receiving neo-adjuvant chemotherapy (typically gemcitabine and cisplatin) and those having either an ileal conduit or a neo-bladder reconstruction. Patients who have selected radical cystectomy after appropriate counselling and following a specialist multi-disciplinary team (SMDT) recommendation, will be approached and asked to consent for this study. Consenting participants will be randomised 1:1 to either iRARC or ORC. Patients will be followed for a minimum of 90 days post-surgery. The study will be conducted in National Health Service (NHS) Trusts designated as Cancer Centres. Patients will be stratified by - Type of urinary diversion (Continent diversion or ileal conduit) - Performance status - Centre Trial assessments will be conducted at baseline (before surgery), whilst participants are on admission and then 5, 12, 26 weeks,1 year and 18 months post surgery.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03049410

    Sponsor: University College, London

    Primary Outcome Measures:

    • Measure: Days at home within 90 days of the surgery
    • Time Frame: 90 days post surgery
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Difficulties due to health conditions measured using WHODAS version 2.0
    • Time Frame: 12 months post surgery
    • Safety Issue:
    • Measure: Quality of Life measured using EQ-5D-5L Health Questionnaire and EORTC QLQ-C30 version 3.
    • Time Frame: 12 months post surgery
    • Safety Issue:

    Estimated Enrollment: 340

    Study Start Date: March 1, 2017

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Participants must be over 18 years of age.
    • Male or female
    • Histopathological confirmation of bladder cancer (UCC, SCC, adenocarcinoma or rare variant)
    • CIS or stage pTa or pT1 or ≥pT2 or mobile bladder mass on bimanual examination under anaesthesia (see Section 22: Definitions for TNM definitions)
    • Node status ≤ N1 on imaging criteria or PET -ve outside pelvis
    • ECOG grade 0, 1, 2 or 3
    • Able to give informed written consent to participate.

    Exclusion Criteria:

    • Unwilling to undergo cystectomy.
    • Previous abdominal surgery rendering them unsuitable for either iRARC or ORC.
    • Patients with upper urinary tract disease
    • Concomitant disease that would render the patient unsuitable for the trial
    • Pregnant or lactating females
    • Previous radiotherapy for bladder cancer

    Contact:

    • Chris Brew-Graves
    • 0207 679 9280

    Locations:

    • North Bristol NHS Trust
    • Bristol United Kingdom
    • Queen Elizabeth University Hospital
    • Glasgow United Kingdom
    • St James' University Hospital
    • Leeds United Kingdom
    • University College London Hospitals NHS Foundation Trust
    • London NW1 2BU United Kingdom
    • Guy's Hospital
    • London United Kingdom
    • Royal Berkshire Hospital
    • Reading United Kingdom
    • Sheffield Teaching Hospitals NHS Foundation Trust
    • Sheffield S10 2JF United Kingdom
    • Lister Hospital
    • Stevenage United Kingdom

    View trial on ClinicalTrials.gov


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    Published October 9, 2017
  • A Phase III Surgical Trial to Evaluate the Benefit of a Standard Versus an Extended Pelvic Lymphadenectomy Performed at Time of Radical Cystectomy for Muscle Invasive Urothelial Cancer

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    A Phase III Surgical Trial to Evaluate the Benefit of a Standard Versus an Extended Pelvic Lymphadenectomy Performed at Time of Radical Cystectomy for Muscle Invasive Urothelial Cancer


    Condition: Bladder Cancer

    Intervention:

    • Procedure: therapeutic conventional surgery
    • Procedure: therapeutic standard lymphadenectomy
    • Procedure: therapeutic extended lymphadenectomy

    Purpose: RATIONALE: Lymphadenectomy may remove tumor cells that have spread to nearby lymph nodes in patients with invasive bladder cancer. It is not yet known whether extended pelvic lymphadenectomy is more effective than standard pelvic lymphadenectomy during surgery. PURPOSE: This randomized phase II trial is studying standard pelvic lymphadenectomy to see how well it works compared to extended pelvic lymphadenectomy in treating patients undergoing surgery for invasive bladder cancer.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT01224665

    Sponsor: Southwest Oncology Group

    Primary Outcome Measures:

    • Measure: Disease-free survival
    • Time Frame: Up to 6 years from date of Step 2 Registration
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Overall survival
    • Time Frame: Up to 6 years from date of Step 2 Registration
    • Safety Issue:
    • Measure: Morbidity
    • Time Frame: Up to 6 years from date of Step 2 Registration
    • Safety Issue:

    Estimated Enrollment: 620

    Study Start Date: August 2011

    Eligibility:

    • Age: minimum 18 Years maximum 120 Years
    • Gender: All

    Disease Characteristics:

    • Histologically confirmed urothelial carcinoma of the bladder
    • Stage T2, T3, or T4a disease
    • No clinical stage consistent with a low-risk of node metastasis (CIS only, T1)
    • No T4b disease (fixed lesion)
    • Disease that requires primary radical cystectomy and lymph node dissection for definitive treatment
    • No laparoscopic surgery
    • Predominant urothelial carcinoma with any of the following elements allowed:
    • Adenocarcinoma
    • Squamous cell carcinoma
    • Micropapillary or minor components of other rare phenotype
    • No pure squamous cell carcinoma or adenocarcinoma
    • No visceral or nodal metastatic disease proximal to the common iliac bifurcation by 2-view chest x-ray and abdominal-pelvic imaging by computerized tomography or MRI of the abdomen and pelvis
    • No intra-operative pelvic lymph node involvement (confirmed by frozen section) at or above the bifurcation of the common iliac vessels in any of the extended template

    Patient Characteristics:

    • Zubrod performance status 0-2
    • ALT and AST ≤ upper limit of normal (ULN)*
    • Alkaline phosphatase ≤ ULN*
    • Not pregnant or nursing
    • Fertile patients must use an effective contraception
    • No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or stage I or II cancer from which the patient is in complete remission for the past 5 years
    • Medically suitable to undergo cystectomy, in the physician's opinion NOTE: *Levels may be ≥ ULN provided metastatic disease is excluded using dedicated liver imaging, bone scan, or biopsy.

    Prior Concurrent Therapy:

    • See Disease Characteristics
    • No prior partial cystectomy for invasive bladder cancer
    • No prior pelvic surgery that would obviate a complete extended lymphadenectomy (e.g., aorto-femoral/iliac bypass)
    • Prior neoadjuvant chemotherapy for this cancer allowed provided it has been completed and patient has recovered
    • No prior pelvic irradiation

    Contact:

    • Jennifer I Scott
    • 210-614-8808 Ext. 1007

    Locations:

    • Los Angeles County-USC Medical Center
    • Los Angeles California 90033 United States
    • USC / Norris Comprehensive Cancer Center
    • Los Angeles California 90033 United States
    • Stanford Cancer Institute
    • Palo Alto California 94304 United States
    • University of California Davis Comprehensive Cancer Center
    • Sacramento California 95817 United States
    • UCSF Medical Center-Mount Zion
    • San Francisco California 94115 United States
    • UCSF Medical Center-Mission Bay
    • San Francisco California 94158 United States
    • University of Colorado Cancer Center - Anschutz Cancer Pavilion
    • Aurora Colorado 80045 United States
    • Yale University
    • New Haven Connecticut 06520 United States
    • Moffitt Cancer Center
    • Tampa Florida 33612 United States
    • University of Chicago Comprehensive Cancer Center
    • Chicago Illinois 60637 United States
    • Loyola University Medical Center
    • Maywood Illinois 60153 United States
    • Louisiana State University Health Sciences Center Shreveport
    • Shreveport Louisiana 71103 United States
    • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Baltimore Maryland 21287 United States
    • Brigham and Women's Hospital
    • Boston Massachusetts 02115 United States
    • Mayo Clinic
    • Rochester Minnesota 55905 United States
    • Washington University School of Medicine
    • Saint Louis Missouri 63110 United States
    • Memorial Sloan-Kettering Cancer Center
    • New York New York 10065 United States
    • University of Rochester
    • Rochester New York 14642 United States
    • Cleveland Clinic Foundation
    • Cleveland Ohio 44195 United States
    • Ohio State University Comprehensive Cancer Center
    • Columbus Ohio 43210 United States
    • Oregon Health and Science University
    • Portland Oregon 97239 United States
    • Portland Veterans Administration Medical Center
    • Portland Oregon 97239 United States
    • Parkland Memorial Hospital
    • Dallas Texas 75235 United States
    • UT Southwestern/Simmons Cancer Center-Dallas
    • Dallas Texas 75390 United States
    • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
    • Houston Texas 77030 United States
    • Baylor Saint Luke's Medical Center
    • Houston Texas 77030 United States
    • M D Anderson Cancer Center
    • Houston Texas 77030 United States
    • Audie L Murphy Veterans Affairs Hospital
    • San Antonio Texas 78209 United States
    • University of Texas Health Science Center at San Antonio
    • San Antonio Texas 78229 United States
    • BCCA-Vancouver Cancer Centre
    • Vancouver British Columbia V5Z 4E6 Canada
    • QEII Health Sciences Centre/Capital District Health Authority
    • Halifax Nova Scotia B3H 1V8 Canada
    • London Regional Cancer Program
    • London Ontario N6A 4L6 Canada
    • University Health Network-Princess Margaret Hospital
    • Toronto Ontario M5G 2M9 Canada
    • McGill University Department of Oncology
    • Montreal Quebec H2W 1S6 Canada
    • The Research Institute of the McGill University Health Centre (MUHC)
    • Montreal Quebec H3H 2R9 Canada

    View trial on ClinicalTrials.gov


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    Published January 25, 2017
  • A Phase III, Open-Label, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Versus Observation as Adjuvant Therapy in Patients With PD-L1-Selected, High-Risk Muscle-Invasive Bladder Cancer After Cystectomy

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    A Phase III, Open-Label, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Versus Observation as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Urothelial Carcinoma After Surgical Resection


    Condition: Carcinoma, Transitional Cell

    Intervention:

    • Drug: Atezolizumab

    Purpose: This Phase III, open-label, randomized, multicenter study is to evaluate the efficacy and safety of adjuvant treatment with atezolizumab compared with observation in participants with muscle-invasive UC who are at high risk for recurrence following resection. Eligible participants will be randomized by a 1:1 ratio into atezolizumab group or control group.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02450331

    Sponsor: Hoffmann-La Roche

    Primary Outcome Measures:

    • Measure: Disease-Free Survival (DFS), as Assessed by Investigator
    • Time Frame: Randomization up to first occurrence of DFS event (assessed at screening/randomization, every 12 weeks after randomization in first 3 years, every 24 weeks for Years 4 and 5, and at Year 6)
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Overall Survival (OS)
    • Time Frame: Randomization until death due to any cause (up to approximately 8 years)
    • Safety Issue:
    • Measure: Disease-Specific Survival (DSS), as Assessed by Investigator
    • Time Frame: Randomization until death due to UC (up to approximately 8 years)
    • Safety Issue:
    • Measure: Distant Metastasis-Free Survival (DMFS)
    • Time Frame: Randomization up to diagnosis of distant metastases or death from any cause (assessed at screening/randomization, every 12 weeks after randomization in first 3 years, every 24 weeks for Years 4 and 5, and at Year 6)
    • Safety Issue:
    • Measure: Non-Urinary Tract Recurrence-Free Survival (NURFS)
    • Time Frame: Randomization up to time of first occurrence of a NURFS event (assessed at screening/randomization, every 12 weeks after randomization in first 3 years, every 24 weeks for Years 4 and 5, and at Year 6)
    • Safety Issue:
    • Measure: Percentage of Participants with Adverse Events (AEs)
    • Time Frame: Screening up to approximately 1 year
    • Safety Issue:
    • Measure: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
    • Time Frame: Pre-dose (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, and every 8 cycles from Cycle 8; at treatment discontinuation (up to 1 year); 120 days after last dose (last dose = up to 1 year) (Cycle length = 21 days)
    • Safety Issue:
    • Measure: European Quality of Life (EuroQoL) Group 5-Dimension 5-Level (EQ-5D-5L) Self Report Questionnaire Health Utility Score
    • Time Frame: Day 1 of Cycle 1 up to 6 years (detailed timeframe is provided in outcome description section)
    • Safety Issue:
    • Measure: Minimum Observed Serum Atezolizumab Concentration (Cmin)
    • Time Frame: Pre-dose (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, every 8 cycles from Cycle 8, at treatment discontinuation (up to 1 year), 120 days after treatment discontinuation (up to 1 year 4 months)
    • Safety Issue:
    • Measure: Maximum Observed Serum Atezolizumab Concentration (Cmax)
    • Time Frame: Pre-dose (Hour 0) and 0.5 hours after end of infusion on Day 1 of Cycle 1 (infusion duration = 60 minutes, Cycle length = 21 days)
    • Safety Issue:

    Estimated Enrollment: 800

    Study Start Date: October 5, 2015

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma) of the bladder or upper urinary tract (i.e., renal pelvis or ureters)
    • For participants treated with prior neoadjuvant chemotherapy: tumor stage of ypT2-4a or ypN+ (ypT2-4 or ypN+ for participants with upper urinary tract UC) and M0
    • For participants who have not received prior neoadjuvant chemotherapy: tumor stage of pT3-4a or pN+ (pT3-4 or pN+ for participants with upper urinary tract UC) and M0
    • Representative formalin-fixed paraffin-embedded tumor specimens from surgical resection (i.e., radical cystectomy, nephroureterectomy, or lymph node dissection) in paraffin blocks (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for central testing and determined to be evaluable for tumor programmed death-ligand 1 (PD-L1) expression prior to study enrollment
    • Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging scan of the pelvis, abdomen, and chest no more than 4 weeks prior to randomization
    • Full recovery from cystectomy or nephroureterectomy within 14 weeks following surgery
    • Eastern Cooperative Oncology Group performance status of less than or equal to (
    • Life expectancy greater than or equal to (>/=) 12 weeks
    • Adequate hematologic and end-organ function
    • For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use contraceptive methods that result in a failure rate of less than (<) 1 percent (%) per year during the treatment period and for at least 5 months after the last dose of atezolizumab

    Exclusion Criteria:

    • Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
    • Adjuvant chemotherapy or radiation therapy for UC following surgical resection
    • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug prior to enrollment
    • Malignancies other than UC within 5 years prior to Cycle 1, Day 1
    • Pregnancy or breastfeeding
    • Significant cardiovascular disease
    • Severe infections within 4 weeks prior to Cycle 1, Day 1
    • Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1
    • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
    • History of autoimmune disease
    • Prior allogeneic stem cell or solid organ transplant
    • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
    • Positive test for human immunodeficiency virus and/or active hepatitis B or hepatitis C or tuberculosis
    • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1
    • Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-CD40, anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies

    Contact:

    • Reference Study ID Number: WO29636 www.roche.com/about_roche/roche_worldwide.htm
    • 888-662-6728 (U.S. and Canada)

    Locations:

    • Mayo Clinic Arizona
    • Phoenix Arizona 85259 United States
    • HonorHealth Research Institute - Pima - Virginia G. Piper Cancer Care Network
    • Scottsdale Arizona 85258 United States
    • CBCC Global Research Inc., at Comprehensive Blood and Cancer Center
    • Bakersfield California 93309 United States
    • UCLA
    • Los Angeles California 90024 United States
    • USC Norris Cancer Center
    • Los Angeles California 90033 United States
    • Central Coast Medical Oncology
    • Los Angeles California 90095-1772 United States
    • Stanford University Medical Center
    • Palo Alto California 94304 United States
    • Torrance Heath Association DBA Torrance Memorial Physican Network / Cancer Care Associate
    • Redondo Beach California 90277 United States
    • Pacific Central Coast Health Centers SLO Oncology and Hematology
    • San Luis Obispo California 93401 United States
    • University Of Colorado
    • Aurora Colorado 80045 United States
    • The Urology Center of Colorado
    • Denver Colorado 80211 United States
    • Yale Cancer Center; Medical Oncology
    • New Haven Connecticut 06520 United States
    • University Of Miami Hospital
    • Miami Florida 33136 United States
    • Northwestern University Feinberg School Of Medicine
    • Chicago Illinois 60611 United States
    • University of Chicago; Hematology/Oncology
    • Chicago Illinois 60637 United States
    • Indiana University
    • Indianapolis Indiana 46202 United States
    • University of Iowa Hospital & Clinic; Division of Hematology/Oncology
    • Iowa City Iowa 52242 United States
    • Cancer Center of Kansas
    • Wichita Kansas 67214 United States
    • Albert B. Chandler Medical Center; University of Kentucky
    • Lexington Kentucky 40536 United States
    • Norton Cancer Institute
    • Louisville Kentucky 40202 United States
    • New England Cancer Specialists
    • Scarborough Maine 04074 United States
    • John Hopkins Sidney Kimmel Comprehensive Cancer Center
    • Baltimore Maryland 21287 United States
    • Chesapeake Urology Research Associates
    • Towson Maryland 21204 United States
    • Massachusetts General Hospital.
    • Boston Massachusetts 02114 United States
    • Dana Farber Cancer Inst.
    • Boston Massachusetts 02115 United States
    • Beth Israel Deaconess Medical Center
    • Boston Massachusetts 02215 United States
    • University Of Michigan
    • Ann Arbor Michigan 48109 United States
    • Karmanos Cancer Institute
    • Detroit Michigan 48201 United States
    • Henry Ford Health System
    • Detroit Michigan 48202 United States
    • University of Minnesota
    • Minneapolis Minnesota 55455 United States
    • Southeast Nebraska Cancer Ctr
    • Lincoln Nebraska 68510 United States
    • MSK @Basking Ridge
    • Basking Ridge New Jersey 07920 United States
    • Saint Barnabas Medical Center Cancer Center
    • Livingston New Jersey 07039 United States
    • Memorial Sloan-Kettering Cancer Center
    • Commack New York 11725 United States
    • MSKCC @ Commack
    • Commack New York 11725 United States
    • MSKCC @ West Harrison
    • Harrison New York 10604 United States
    • Monter Cancer Center
    • Lake Success New York 11042 United States
    • Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
    • New York New York 10016 United States
    • Columbia University Medical Center
    • New York New York 10032 United States
    • MSKC @ Rockville
    • Rockville Centre New York 11570 United States
    • MSKCC at Sleepy Hollow
    • Sleepy Hollow New York 10591 United States
    • Associated Medical Professionals of NY, PLLC
    • Syracuse New York 13210-1155 United States
    • Levine Cancer Institute
    • Charlotte North Carolina 28204 United States
    • Duke Cancer Center
    • Durham North Carolina 27710 United States
    • Wake Forest University Baptist Medical Center
    • Winston-Salem North Carolina 27157 United States
    • Cleveland Clinic
    • Cleveland Ohio 44106 United States
    • Fairview Hospital; Cleveland Clinic Cancer Center
    • Cleveland Ohio 44111 United States
    • The Ohio State University Wexner Medical Center
    • Columbus Ohio 43212 United States
    • Hillcrest Hospital; Hirsch Cancer Center
    • Mayfield Heights Ohio 44124 United States
    • Cleveland CL N Coast Cancer Cr
    • Sandusky Ohio 44870 United States
    • St. Luke's University Health network
    • Bethlehem Pennsylvania 18015 United States
    • Penn State Milton S. Hershey Medical Center
    • Hershey Pennsylvania 17033 United States
    • Abramson Cancer Center; Univ of Pennsylvania
    • Philadelphia Pennsylvania 19104 United States
    • Kimmel Cancer Center Thomas Jefferson University
    • Philadelphia Pennsylvania 19107 United States
    • Fox Chase-Temple Cancer Center
    • Philadelphia Pennsylvania 19111 United States
    • Miriam Hospital
    • Providence Rhode Island 02906 United States
    • University of Texas Southwestern
    • Dallas Texas 75390-8897 United States
    • Baylor College of Medicine; Gastroenterology
    • Houston Texas 77030 United States
    • University of Texas Health Science Center at San Antonio
    • San Antonio Texas 78229 United States
    • University of Virginia
    • Charlottesville Virginia 22906 United States
    • Seattle Cancer Care Alliance
    • Seattle Washington 98109 United States
    • Macquarie University Hospital
    • Sydney New South Wales 2109 Australia
    • Royal Brisbane & Women's Hosp; Cancer Care Serv
    • Herston Queensland 4029 Australia
    • Monash Medical Centre; Oncology
    • Clayton Victoria 3168 Australia
    • Austin and Repatriation Medical Centre; Cancer Services
    • Melbourne Victoria 3084 Australia
    • Healthcare Institution "Gomel Regional Clinical Oncologic Dispensary"
    • Gomel 246012 Belarus
    • N.N. Alexandrov National Cancer Centre of Belarus
    • Minsk District 223040 Belarus
    • Minsk City Clinical Oncologic Dispensary
    • Minsk BU-220013 Belarus
    • Vitebsk Regional Clinical Oncology Dispensary
    • Vitebsk BU-210603 Belarus
    • ZNA Middelheim
    • Antwerpen 2020 Belgium
    • Institut Jules Bordet
    • Bruxelles 1000 Belgium
    • Cliniques Universitaires St-Luc
    • Bruxelles 1200 Belgium
    • UZ Gent
    • Gent 9000 Belgium
    • UZ Leuven Gasthuisberg
    • Leuven 3000 Belgium
    • Sint Augustinus Wilrijk
    • Wilrijk 2610 Belgium
    • Cross Cancer Institute ; Dept of Medical Oncology
    • Edmonton Alberta T6G 1Z2 Canada
    • BCCA-Vancouver Cancer Centre
    • Vancouver British Columbia V5Z 4E6 Canada
    • Queen Elizabeth II Health Sciences Centre; Oncology
    • Halifax Nova Scotia B3H 2Y9 Canada
    • Royal Victoria Hospital
    • Barrie Ontario L4M 6M2 Canada
    • London Regional Cancer Centre
    • London Ontario N6A 4L6 Canada
    • Lakeridge Health Oshawa; Oncology
    • Oshawa Ontario L1G 2B9 Canada
    • The Ottawa Hospital Cancer Centre; Oncology
    • Ottawa Ontario K1H 8L6 Canada
    • North York General Hospital
    • Toronto Ontario M2J 1V1 Canada
    • Sunnybrook Odette Cancer Centre
    • Toronto Ontario M4N 3M5 Canada
    • McGill University; Glen Site; Oncology
    • Montreal Quebec H4A 3J1 Canada
    • Centre Hospitalier universitaire de Québec/ Hotel Dieu de Québec
    • Quebec G1R 3S1 Canada
    • Cancer Hospital Chinese Academy of Medical Sciences.
    • Beijing 100021 China
    • Peking University First Hospital
    • Beijing 100034 China
    • Friendship Hospital, Capital Medical University
    • Beijing 100050 China
    • Peking University Third Hospital
    • Beijing 100083 China
    • Beijing Cancer Hospital
    • Beijing 100142 China
    • the First Hospital of Jilin University
    • Changchun 130021 China
    • Hu Nan Provincial Cancer Hospital
    • Changsha 410006 China
    • The Second Affiliated Hospital, Sun Yat-sen University
    • Guangzhou City 510120 China
    • Sun Yet-sen University Cancer Center
    • Guangzhou 510060 China
    • Jiangsu Cancer Hospital
    • Nanjing 210009 China
    • Jiangsu Province Hospital
    • Nanjing 210036 China
    • Huashan Hospital Affiliated to Fudan University
    • Shanghai City 200040 China
    • Fudan University Shanghai Cancer Center
    • Shanghai 200032 China
    • Zhongshan Hospital Fudan University
    • Shanghai 200032 China
    • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
    • Shanghai 200092 China
    • Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
    • Shanghai 200127 China
    • Tianjin Cancer Hospital; urologic tumor
    • Tianjin City 300060 China
    • The 2nd Hospital of Tianjin Medical University
    • Tianjin 201203 China
    • Masarykuv onkologicky ustav
    • Brno 656 53 Czechia
    • University Hospital Olomouc
    • Olomouc 77520 Czechia
    • Hospital Pardubice
    • Pardubice 532 03 Czechia
    • University Hospital Motol; Department of Urology
    • Praha 5 15006 Czechia
    • Helsinki University Central Hospital; Urology Clinics
    • Helsinki 00029 Finland
    • Tampere University Hospital; Dept Of Urology
    • Tampere 33520 Finland
    • Turku University Central Hospital; Urology clinic
    • Turku 20520 Finland
    • ICO Paul Papin; Oncologie Medicale.
    • Angers 49055 France
    • Institut Sainte Catherine;Recherche Clinique
    • Avignon 84918 France
    • Hopital Saint Andre
    • Bordeaux 33075 France
    • Centre Francois Baclesse; Recherche Clinique
    • Caen 14076 France
    • Centre Jean Perrin
    • Clermont Ferrand 63011 France
    • Centre Leon Berard; Departement Oncologie Medicale
    • Lyon 69373 France
    • Centre D'Oncologie de Gentilly; Oncology
    • Nancy 54100 France
    • Centre Antoine Lacassagne
    • Nice 06189 France
    • Hopital Cochin; Unite Fonctionnelle D Oncologie
    • Paris 75014 France
    • Hopital Saint Louis; Oncologie Medicale
    • Paris 75475 France
    • Institut Mutualiste Montsouris; Oncologie
    • Paris 75674 France
    • Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale
    • Paris 75908 France
    • ICO - Site René Gauducheau
    • Saint Herblain 44805 France
    • Institut Claudius Regaud; Departement Oncologie Medicale
    • Toulouse 31059 France
    • Institut Gustave Roussy; Departement Oncologie Medicale
    • Villejuif 94805 France
    • Uniklinik RWTH Aachen; Klinik für Urologie
    • Aachen 52074 Germany
    • Charité - Universitätsmedizin Berlin; CC 8: Chirurgische Medizin; Klinik für Urologie
    • Berlin 12200 Germany
    • Augusta-Kranken-Anstalt gGmbH; Klinik für Hämatologie, Onkologie & Palliativmedizin
    • Bochum 44791 Germany
    • Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Urologie
    • Dresden 01307 Germany
    • Universitätsklinikum Düsseldorf; Urologische Klinik
    • Düsseldorf 40225 Germany
    • Uniklinik Essen; Urologische Klinik & Poliklinik
    • Essen 45122 Germany
    • Asklepios Klinik Altona, Abteilung für Urologie
    • Hamburg 22763 Germany
    • Universitätsklinikum der Ruhr-Universität Bochum, Marien-Hospital Herne, Urologische Klinik
    • Herne 44625 Germany
    • Universitätsklinikum des Saarlandes; Klinik für Urologie und Kinderurologie
    • Homburg/Saar 66424 Germany
    • Medizinische Fakultät Mannheim, Universitätsklinikum Mannheim, Klinik für Urologie
    • Mannheim 68167 Germany
    • Klinikum rechts der Isar der TU München; Urologische Klinik und Poliklinik
    • München 81675 Germany
    • Universitätsmedizin Rostock, Urologische Klinik und Poliklinik
    • Rostock 18057 Germany
    • Diakonie-Klinikum Stuttgart, Urologische Klinik
    • Stuttgart 70176 Germany
    • Universitätsklinikum Tübingen; Klinik für Urologie
    • Tübingen 72076 Germany
    • Universitätsklinikum Ulm; Klinik für Urologie
    • Ulm 89081 Germany
    • Alexandras General Hospital of Athens; Oncology Department
    • Athens 115 28 Greece
    • University Hospital of Patras Medical Oncology
    • Patras 265 04 Greece
    • Rambam Health Care Campus; Oncology - Hafia
    • Hafia 3109601 Israel
    • Shaare Zedek Medical Center; Oncology Dept
    • Jerusalem 91031 Israel
    • Hadassah Ein Karem Hospital; Oncology Dept
    • Jerusalem 9112001 Israel
    • Meir Medical Center; Oncology
    • Kfar-Saba 4428164 Israel
    • Rabin Medical Center; Oncology Dept
    • Petach Tikva 4941492 Israel
    • Chaim Sheba Medical Center; Oncology Dept
    • Ramat Gan 5262100 Israel
    • Tel-Aviv Sourasky Medical Center
    • Tel Aviv 6423906 Israel
    • Assaf Harofeh; Oncology
    • Zerifin 6093000 Israel
    • Az. Osp. Cardarelli; Divisione Di Oncologia
    • Napoli Campania 80131 Italy
    • ISTITUTO NAZIONALE TUMORI IRCCS FONDAZIONE G. PASCALE; Dipartimento Uro-Ginecologico
    • Napoli Campania 80131 Italy
    • Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
    • Bologna Emilia-Romagna 40138 Italy
    • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
    • Meldola Emilia-Romagna 47014 Italy
    • Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica
    • Roma Lazio 00152 Italy
    • Irccs Ospedale San Raffaele;Oncologia Medica
    • Milano Lombardia 20132 Italy
    • Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche
    • Milano Lombardia 20141 Italy
    • A.O. UNIVERSITARIA S. LUIGI GONZAGA; Oncologia Medica
    • Orbassano Piemonte 10043 Italy
    • Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia
    • Arezzo Toscana 52100 Italy
    • Azienda Ospedaliera S. Maria - Terni; Oncologia
    • Terni Umbria 05100 Italy
    • Nagoya University Hospital; Urology
    • Aichi 466-8560 Japan
    • Hirosaki University School of Medicine & Hospital; Urology
    • Aomori 036-8563 Japan
    • Shikoku Cancer Center
    • Ehime 791-0280 Japan
    • Hiroshima City Hiroshima Citizens Hospital; Urology
    • Hiroshima 730-8518 Japan
    • National Hospital Organization Hokkaido Cancer Center
    • Hokkaido 003-0804 Japan
    • University of Tsukuba Hospital
    • Ibaraki 305-8576 Japan
    • Iwate Medical University Hospital; Urology
    • Iwate 020-8505 Japan
    • Kyoto University Hospital
    • Kyoto 606-8507 Japan
    • Niigata University Medical & Dental Hospital
    • Niigata 951-8520 Japan
    • Okayama University Hospital
    • Okayama 700-8558 Japan
    • Osaka University Hospital; Urology
    • Osaka 565-0871 Japan
    • Kindai University Hospital; Urology
    • Osaka 589-8511 Japan
    • Saitama Medical University International Medical Center
    • Saitama 350-1298 Japan
    • Shizuoka Cancer Center; Urology
    • Shizuoka 411-8777 Japan
    • National Cancer Center Hospital; Urology
    • Tokyo 104-0045 Japan
    • The University of Tokyo Hospital
    • Tokyo 113-8655 Japan
    • The Cancer Institute Hospital, JFCR; Urology
    • Tokyo 135-8550 Japan
    • Tokyo Women's Medical University Hospital
    • Tokyo 162-8666 Japan
    • Kyorin University Hospital
    • Tokyo 181-8611 Japan
    • National Cancer Center
    • Gyeonggi-do 10408 Korea, Republic of
    • Severance Hospital, Yonsei University Health System; Pharmacy
    • Seoul 03722 Korea, Republic of
    • Asan Medical Center
    • Seoul 05505 Korea, Republic of
    • Samsung Medical Center
    • Seoul 6351 Korea, Republic of
    • NKI/AvL
    • Amsterdam 1066 CX Netherlands
    • VU MEDISCH CENTRUM; Dept. of Medical Oncology
    • Amsterdam 1081 HV Netherlands
    • Academ Ziekenhuis Groningen; Medical Oncology
    • Groningen 9713 GZ Netherlands
    • UMC Radboud Nijmegen
    • Nijmegen 6500 HB Netherlands
    • Erasmus Mc - Daniel Den Hoed Kliniek; Interne Oncologie
    • Rotterdam 3015AA Netherlands
    • St. Antonius locatie Leidsche Rijn
    • Utrecht 3543 AZ Netherlands
    • KO-MED Centra Kliniczne Lublin II
    • Lublin 20-362 Poland
    • Oddzial Chemioterapii Szpitala Klinicznego Nr 1 w Poznaniu
    • Poznan 60-569 Poland
    • SpecjalistycznySzpital Miejski w Toruniu; Oddział Urologii Ogólnej i Onkologicznej
    • Toruń 87-100 Poland
    • Szpital Kliniczny Dzieciątka Jezus; Oddział Urologii
    • Warszawa 02-005 Poland
    • Centralny Szpital Kliniczny Mswia; Klinika onkologii, hematologii i chorob wewnetrznych
    • Warszawa 02-507 Poland
    • Międzyleski Szpital Specjalistyczny; Oddział Urologii
    • Warszawa 04-749 Poland
    • Uniwersytecki Szpital Kliniczny im. Jana Miklulicza-Radeckiego we Wrocławiu; Departament Of Urology
    • Wroclaw 50-556 Poland
    • GBUZ Nizhegorodskay Region: Clinical Diagnostic Center
    • Nizhni Novgorod Niznij Novgorod 603001 Russian Federation
    • Sverdlovsk Regional Oncology Dispensary; Chemotherapy
    • Ekaterinburg 620905 Russian Federation
    • Ivanovo Regional Oncology Dispensary
    • Ivanovo 153040 Russian Federation
    • Ctr Clinical Hosptial of President'S Affairs Board; Oncology
    • Moscow 121356 Russian Federation
    • P.A. Herzen Oncological Inst. ; Oncology
    • Moscow 125284 Russian Federation
    • Privolzhsk Regional Medical Center
    • Nizhny Novgorod 603001 Russian Federation
    • City Clinical Oncology Dispensary
    • Saint-Petersburg 197022 Russian Federation
    • MCMC Medical City; Oncology
    • Tumen 625047 Russian Federation
    • SBEI of HPE "Bashkir State Medical University" of MoH RF
    • Ufa 450000 Russian Federation
    • Clinic for Urology; Clinical Hospital Center "Dragisa Misovic-Dedinje"
    • Belgrade 11000 Serbia
    • Clinic for Urology; Military Medical Academy
    • Belgrade 11000 Serbia
    • Clinical Center of Serbia; Clinic of Urology
    • Belgrade 11000 Serbia
    • Clinical Center of Vojvodina
    • Novi Sad 21000 Serbia
    • Oncology Institute of Vojvodina
    • Sremska Kamenica 21204 Serbia
    • Hospital Univ. Central de Asturias; Servicio de Oncologia
    • Oviedo Asturias 33011 Spain
    • Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
    • Sabadell Barcelona 08208 Spain
    • Hospital de Donostia; Servicio de Oncologia Medica
    • San Sebastian Guipuzcoa 20080 Spain
    • Hospital Univ Vall d'Hebron; Servicio de Oncologia
    • Barcelona 08035 Spain
    • Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department
    • Barcelona 08036 Spain
    • Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia
    • Barcelona 08041 Spain
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
    • Madrid 28007 Spain
    • Hospital Ramon y Cajal; Servicio de Oncologia
    • Madrid 28034 Spain
    • Hospital Clinico San Carlos; Servicio de Oncologia
    • Madrid 28040 Spain
    • Hospital Universitario 12 de Octubre; Servicio de Oncologia
    • Madrid 28041 Spain
    • Hospital Universitario La Paz; Servicio de Oncologia
    • Madrid 28046 Spain
    • Instituto Valenciano Oncologia; Oncologia Medica
    • Valencia 46009 Spain
    • UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie
    • Zürich 8091 Switzerland
    • Taichung Veterans General Hospital; Division of Urology
    • Taichung 407 Taiwan
    • National Taiwan University Hospital, Department of Urology
    • Taipei 10048 Taiwan
    • Chang Gung Medical Foundation-Linkou, Urinary Oncology
    • Taoyuan 333 Taiwan
    • Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology
    • Adana 01250 Turkey
    • Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department
    • Edirne 22770 Turkey
    • Bezmialem Vakif Univ Medical; Bezmialem Vakif Univ T
    • Istanbul 34093 Turkey
    • Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology
    • Istanbul 34300 Turkey
    • Ege Uni Medical Faculty; Oncology Dept
    • Izmir 35100 Turkey
    • Medikal Park Izmir Hospital
    • Karşıyaka 35575 Turkey
    • Hacettepe Uni Medical Faculty Hospital; Oncology Dept
    • Sıhhiye, Ankara 06100 Turkey
    • Regional Clinical Center of Urology and Nephrology n.a. V.I. Shapoval Department of Urology #4
    • Kharkiv Kharkiv Governorate 61037 Ukraine
    • CI Dnipropetrovsk CMCH #4 MA of MOHU Ch of Oncology and MR
    • Dnipropetrovsk 49102 Ukraine
    • GU "Institution of urology of Academy Medical science of Ukraine"
    • Kiev 04053 Ukraine
    • Lviv State Oncology Regional Treatment and Diagnostic Centre; Department of hemotherapy
    • Lviv 79031 Ukraine
    • Zaporozhye Regional Oncology Hospital; Dept of Oncology
    • Zaporozhye 69104 Ukraine
    • University Hospitals Birmingham NHS Foundation Trust
    • Birmingham B15 2TH United Kingdom
    • University Hospitals Bristol NHS Foundation Trust
    • Bristol BS2 8BJ United Kingdom
    • Beatson West of Scotland Cancer Centre
    • Glasgow G12 0YN United Kingdom
    • Barts Health NHS Trust - St Bartholomew's Hospital
    • London EC1A 7BE United Kingdom
    • Sarah Cannon Research Institute
    • London W1G 6AD United Kingdom
    • James Cook Uni Hospital
    • Middlesborough TS4 3BW United Kingdom
    • Churchill Hospital
    • Oxford OX3 7LJ United Kingdom
    • Royal Preston Hosptial
    • Preston PR2 9HT United Kingdom
    • Southampton General Hospital
    • Southampton SO16 6YD United Kingdom

    View trial on ClinicalTrials.gov


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    Published February 13, 2017
  • A Phase III, Randomized, Open-Label, Multi-Center, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Gemcitabine+Cisplatin for Neoadjuvant Treatment Followed by Durvalumab Alone for Adjuvant Treatment in Patients With Mus

    {{header-clinical-trials-navigation}}

    A Phase III, Randomized, Open-Label, Multi-Center, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Gemcitabine+Cisplatin for Neoadjuvant Treatment Followed by Durvalumab Alone for Adjuvant Treatment in Patients With Muscle-Invasive Bladder Cancer


    Condition: Muscle Invasive Bladder Cancer

    Intervention:

    • Drug: Durvalumab
    • Drug: Cisplatin
    • Drug: Gemcitabine

    Purpose: A Global Study to Determine the Efficacy and Safety of Durvalumab in Combination with Gemcitabine+Cisplatin for Neoadjuvant Treatment and Durvalumab Alone for Adjuvant Treatment in Patients with Muscle-Invasive Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03732677

    Sponsor: AstraZeneca

    Primary Outcome Measures:

    • Measure: Pathologic complete response (pCR) rates at time of cystectomy following neoadjuvant treatment, as assessed by central pathology review
    • Time Frame: Up to 6 months
    • Safety Issue:
    • Measure: Event-free survival (EFS) per central review defined as time from randomization to the first recurrence of disease (after cystectomy), or progression in patients who were precluded for cystectomy, or death due to any cause, whichever occurs first
    • Time Frame: Up to 48 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Proportion of patients who achieve
    • Time Frame: Up to 6 months
    • Safety Issue:
    • Measure: EFS at 24 months (EFS24) defined as time from randomization to the first recurrence of disease (after cystectomy), or first progression in patients who were precluded for cystectomy, or death due to any cause, whichever occurs first
    • Time Frame: Up to 24 months
    • Safety Issue:
    • Measure: Proportion of patients who undergo cystectomy
    • Time Frame: Up to 6 months
    • Safety Issue:
    • Measure: Overall survival rate at 5 years, as determined based on time from date of randomization to date of death, from any cause
    • Time Frame: Up to 60 months
    • Safety Issue:
    • Measure: PFS2 defined as the time from the date of randomization to the earliest date of progression which occurs on subsequent therapy following an EFS event or death
    • Time Frame: Up to 84 months
    • Safety Issue:
    • Measure: Safety and Tolerability as evaluated by adverse events occurring throughout the study
    • Time Frame: Up to 84 months
    • Safety Issue:
    • Measure: Immunogenicity of durvalumab when used in combination with gemcitabine/cisplatin as measured by presence of antidrug antibodies (ADA)
    • Time Frame: Up to 12 months
    • Safety Issue:

    Estimated Enrollment: 1050

    Study Start Date: November 16, 2018

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum 130 Years
    • Gender: All

    Criteria: Inclusion: - Patient resectable muscle-invasive bladder cancer with clinical stage T2N0M0-T4aN0M0 with transitional cell histology - Patients must be planning to undergo a radical cystectomy at the time of randomization - Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC - ECOG performance status of 0 or 1 - Must have a life expectancy of at least 12 weeks at randomization Exclusion: - Evidence of lymph node or metastatic disease at time of screening. - Prior pelvic radiotherapy treatment within 2 years of randomization to study - Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin [BCG]), including but not limited to other anti-CTLA-4, anti-PD-1, anti PD-L1, or anti-PD-L2 antibodies. - Current or prior use of immunosuppressive medication within 14 days before the first dose of investigational product (IP). The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection); Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent; Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) - Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. - Uncontrolled intercurrent illness - Active infection including Tuberculosis, Hepatitis B, Hepatitis C, and Human Immunodeficiency

    Contact:

    • AstraZeneca Clinical Study Information Center
    • 1-877-240-9479

    Locations:

    • Research Site
    • Birmingham Alabama 35294 United States
    • Research Site
    • Fountain Valley California 92708 United States
    • Research Site
    • Fullerton California 92835 United States
    • Research Site
    • Los Angeles California 90095 United States
    • Research Site
    • Monterey California 93940 United States
    • Research Site
    • Salinas California 93901 United States
    • Research Site
    • Santa Rosa California 95403 United States
    • Research Site
    • Stanford California 94305-5824 United States
    • Research Site
    • Denver Colorado 80211 United States
    • Research Site
    • New Haven Connecticut 06520 United States
    • Research Site
    • Tampa Florida 33612 United States
    • Research Site
    • Chicago Illinois 60611 United States
    • Research Site
    • Iowa City Iowa 52242 United States
    • Research Site
    • Westwood Kansas 66205 United States
    • Research Site
    • Louisville Kentucky 40202 United States
    • Research Site
    • New Orleans Louisiana 70112 United States
    • Research Site
    • New Orleans Louisiana 70121 United States
    • Research Site
    • Baltimore Maryland 21204 United States
    • Research Site
    • Ann Arbor Michigan 48109 United States
    • Research Site
    • Detroit Michigan 48201 United States
    • Research Site
    • Neptune New Jersey 07754 United States
    • Research Site
    • New Brunswick New Jersey 08903 United States
    • Research Site
    • New York New York 10029 United States
    • Research Site
    • Rochester New York 14642 United States
    • Research Site
    • Durham North Carolina 27710 United States
    • Research Site
    • Columbus Ohio 43210 United States
    • Research Site
    • Bethlehem Pennsylvania 18015 United States
    • Research Site
    • Providence Rhode Island 02903 United States
    • Research Site
    • Burlington Vermont 05401 United States
    • Research Site
    • Milwaukee Wisconsin 53226 United States
    • Research Site
    • Box Hill 3128 Australia
    • Research Site
    • Elizabeth Vale 5112 Australia
    • Research Site
    • Herston 4029 Australia
    • Research Site
    • Macquarie University 2109 Australia
    • Research Site
    • Murdoch 6150 Australia
    • Research Site
    • Prahran 3004 Australia
    • Research Site
    • South Brisbane 4101 Australia
    • Research Site
    • Woolloongabba 4102 Australia
    • Research Site
    • Brugge 8000 Belgium
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    • Charleroi 6000 Belgium
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    • Kortrijk 8500 Belgium
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    • Leuven 3000 Belgium
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    • Liège 4000 Belgium
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    • Barretos 14784-400 Brazil
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    • Passo Fundo 99010-080 Brazil
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    • Porto Alegre 90020-090 Brazil
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    • Porto Alegre 90470-340 Brazil
    • Research Site
    • Porto Alegre 90610-000 Brazil
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    • Porto Alegre 91350-200 Brazil
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    • Rio de Janeiro 20231-050 Brazil
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    • Sao Paulo 01323-903 Brazil
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    • Sao Paulo 01509-900 Brazil
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    • Sao Paulo 04101-000 Brazil
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    • São José do Rio Preto 15090-000 Brazil
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    • São Paulo 01246-000 Brazil
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    • São Paulo 03102-002 Brazil
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    • Edmonton Alberta T6G 1Z2 Canada
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    • Vancouver British Columbia V5Z 4E6 Canada
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    • Hamilton Ontario L8V 5C2 Canada
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    • London Ontario N6A 5W9 Canada
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    • Ottawa Ontario K1H 8L6 Canada
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    • Toronto Ontario M5G IX6 Canada
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    • Montreal Quebec H2X 0C2 Canada
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    • Sherbrooke Quebec J1H 5N4 Canada
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    • Antofagasta 1267348 Chile
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    • Puerto Montt 5480000 Chile
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    • Santiago de Chile 6770128 Chile
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    • Santiago 7520349 Chile
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    • Temuco 4810218 Chile
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    • Viña del Mar 2540488 Chile
    • Research Site
    • Brno 656 53 Czechia
    • Research Site
    • Hradec Kralove 500 05 Czechia
    • Research Site
    • Olomouc 779 00 Czechia
    • Research Site
    • Praha 5 150 06 Czechia
    • Research Site
    • Praha 180 81 Czechia
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    • Angers Cedex 01 49033 France
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    • Dijon 21079 France
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    • Grenoble Cedex 09 38043 France
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    • Montpellier 34070 France
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    • Nimes 30029 France
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    • Pierre Benite 69495 France
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    • Poitiers Cedex 86021 France
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    • Rouen F-76031 CE France
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    • Bonn 53127 Germany
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    • Erlangen 91054 Germany
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    • Herne 44625 Germany
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    • Köln 50937 Germany
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    • Magdeburg 39120 Germany
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    • Mannheim 68167 Germany
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    • Nürnberg 90491 Germany
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    • Regensburg 93053 Germany
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    • Ulm 89081 Germany
    • Research Site
    • Würzburg 97080 Germany
    • Research Site
    • Haifa 31096 Israel
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    • Jerusalem 91120 Israel
    • Research Site
    • Kfar Saba 95847 Israel
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    • Petach-Tikva 4941492 Israel
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    • Ramat Gan 52621 Israel
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    • Bari 70124 Italy
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    • Bologna 40138 Italy
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    • Firenze 50134 Italy
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    • Milano 20133 Italy
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    • Napoli 80131 Italy
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    • Orbassano 10043 Italy
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    • Verona 37134 Italy
    • Research Site
    • Bunkyo-ku 113-8603 Japan
    • Research Site
    • Fukuoka-shi 811-1347 Japan
    • Research Site
    • Fukuoka 812-8582 Japan
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    • Hirosaki-shi 036-8563 Japan
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    • Hiroshima-shi 730-8518 Japan
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    • Kanazawa-shi 920-8641 Japan
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    • Koto-ku 135-8550 Japan
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    • Kumamoto-shi 860-0008 Japan
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    • Miyazaki-city 889-1692 Japan
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    • Nagasaki-shi 852-8501 Japan
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    • Nagoya-shi 466-8560 Japan
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    • Niigata-shi 951-8520 Japan
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    • Osaka-shi 541-8567 Japan
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    • Osaka-shi 545-8586 Japan
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    • Osakasayama-shi 589-8511 Japan
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    • Sendai-shi 980-0872 Japan
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    • Shinjuku-ku 160-8582 Japan
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    • Toyama-shi 930-0194 Japan
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    • Tsukuba-shi 305-8576 Japan
    • Research Site
    • Yokohama-shi 232-0024 Japan
    • Research Site
    • Yokohama-shi 241-8515 Japan
    • Research Site
    • Daegu 41404 Korea, Republic of
    • Research Site
    • Goyang-si 10408 Korea, Republic of
    • Research Site
    • Incheon 21565 Korea, Republic of
    • Research Site
    • Seongnam 13620 Korea, Republic of
    • Research Site
    • Seoul 03080 Korea, Republic of
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    • Seoul 136-705 Korea, Republic of
    • Research Site
    • Amsterdam 1066 CX Netherlands
    • Research Site
    • Amsterdam 1081 HV Netherlands
    • Research Site
    • Breda 4819 EV Netherlands
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    • Rotterdam 3015 GD Netherlands
    • Research Site
    • Baguio City 2600 Philippines
    • Research Site
    • Cebu 6000 Philippines
    • Research Site
    • Davao City 8000 Philippines
    • Research Site
    • Makati 1229 Philippines
    • Research Site
    • Manila 1015 Philippines
    • Research Site
    • Quezon City 1101 Philippines
    • Research Site
    • Quezon City 1104 Philippines
    • Research Site
    • Bialystok 15-027 Poland
    • Research Site
    • Gdańsk 80-214 Poland
    • Research Site
    • Grudziądz 86-300 Poland
    • Research Site
    • Koszalin 75-581 Poland
    • Research Site
    • Olsztyn 10-228 Poland
    • Research Site
    • Poznan 60-693 Poland
    • Research Site
    • Radom 26-600 Poland
    • Research Site
    • Warszawa 02-781 Poland
    • Research Site
    • Wroclaw 53-413 Poland
    • Research Site
    • Ivanovo 153040 Russian Federation
    • Research Site
    • Krasnoyarsk 660133 Russian Federation
    • Research Site
    • Moscow 105077 Russian Federation
    • Research Site
    • Nizhniy Novgorod 603074 Russian Federation
    • Research Site
    • Omsk 644013 Russian Federation
    • Research Site
    • Samara 443031 Russian Federation
    • Research Site
    • St. Petersburg 194017 Russian Federation
    • Research Site
    • St. Petersburg 194354 Russian Federation
    • Research Site
    • Vologda 160012 Russian Federation
    • Research Site
    • Badalona 08916 Spain
    • Research Site
    • Barcelona 08035 Spain
    • Research Site
    • Córdoba 14004 Spain
    • Research Site
    • Las Palmas de Gran Canaria 35016 Spain
    • Research Site
    • Madrid 28007 Spain
    • Research Site
    • Madrid 28041 Spain
    • Research Site
    • Santander 39008 Spain
    • Research Site
    • Sevilla 41013 Spain
    • Research Site
    • Kaohsiung 807 Taiwan
    • Research Site
    • Taichung 404 Taiwan
    • Research Site
    • Taichung 40705 Taiwan
    • Research Site
    • Tainan 704 Taiwan
    • Research Site
    • Tainan 710 Taiwan
    • Research Site
    • Taipei City 10050 Taiwan
    • Research Site
    • Taipei 11217 Taiwan
    • Research Site
    • Taoyuan City 333 Taiwan
    • Research Site
    • Ankara 06590 Turkey
    • Research Site
    • Edirne 22030 Turkey
    • Research Site
    • Istanbul 34030 Turkey
    • Research Site
    • Izmir Turkey
    • Research Site
    • Edinburgh EH4 2XR United Kingdom
    • Research Site
    • Guildford GU2 7WG United Kingdom
    • Research Site
    • London E1 1BB United Kingdom
    • Research Site
    • Nottingham NG5 1PB United Kingdom
    • Research Site
    • Sheffield S10 2SJ United Kingdom
    • Research Site
    • Wirral CH63 4JY United Kingdom
    • Research Site
    • Hanoi 100000 Vietnam
    • Research Site
    • Ho Chi Minh city 700000 Vietnam
    • Research Site
    • Ho Chi Minh 700000 Vietnam
    • Research Site
    • Hochiminh 700000 Vietnam

    View trial on ClinicalTrials.gov


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    Published November 6, 2018
  • A Pilot Pre-Surgical Study Evaluating Anti-PD-L1 Antibody (Durvalumab) Plus Anti-CTLA-4 (Tremelimumab) in Patients With Muscle-Invasive, High-Risk Urothelial Carcinoma Who Are Ineligible for Cisplatin-Based Neoadjuvant Chemotherapy

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    A Pilot Pre-Surgical Study Evaluating Anti-PD-L1 Antibody (Durvalumab) Plus Anti-CTLA-4 (Tremelimumab) in Patients With Muscle-Invasive, High-Risk Urothelial Carcinoma Who Are Ineligible for Cisplatin-Based Neoadjuvant Chemotherapy


    Condition: Hydronephrosis, Infiltrating Bladder Urothelial Carcinoma Sarcomatoid Variant, Infiltrating Bladder Urothelial Carcinoma, Micropapillary Variant, Infiltrating Bladder Urothelial Carcinoma, Plasmacytoid Variant, Infiltrating Renal Pelvis Urothelial Carcinoma, Sarcomatoid Variant, Renal Pelvis Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma AJCC v6 and v7, Stage II Renal Pelvis Cancer AJCC v7, Stage II Ureter Cancer AJCC v7, Stage II Urethral Cancer AJCC v7, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, Stage III Renal Pelvis Cancer AJCC v7, Stage III Ureter Cancer AJCC v7, Stage III Urethral Cancer AJCC v7, Stage IV Renal Pelvis Cancer AJCC v7, Stage IV Ureter Cancer AJCC v7, Stage IV Urethral Cancer AJCC v7, Ureter Urothelial Carcinoma, Urethral Urothelial Carcinoma

    Intervention:

    • Biological: Durvalumab
    • Procedure: Therapeutic Conventional Surgery
    • Biological: Tremelimumab

    Purpose: This pilot phase I trial studies the side effects of durvalumab and tremelimumab in treating patients with muscle-invasive, high-risk urothelial cancer that cannot be treated with cisplatin-based therapy before surgery. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02812420

    Sponsor: M.D. Anderson Cancer Center

    Primary Outcome Measures:

    • Measure: Incidence of adverse events determined by extreme toxicity
    • Time Frame: Up to 90 days after last dose of treatment
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Change in immune and molecular responses in peripheral blood and tumor tissues
    • Time Frame: Baseline to 17 weeks
    • Safety Issue:
    • Measure: Pathologic down-staging to T0 disease
    • Time Frame: Up to 1 year
    • Safety Issue:

    Estimated Enrollment: 45

    Study Start Date: March 7, 2017

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Patients must have tissue resected by transurethral resection of bladder tissue (TURBT) at the MD Anderson Cancer Center
    • Patients must have histologic proof of urothelial cancer; this includes bladder cancer, in addition to other tumors of the urothelial lining including renal pelvis, ureteral, and urethral cancer; upper tract urothelial carcinoma will also be included; this group may include any patient requiring cystectomy (or applicable surgery to resect tumors), including muscle invasive disease (cT2-3aN0M0), whose tumor could not be completely removed at transurethral resection
    • Patients with the following high-risk features who are not candidates for traditional neoadjuvant chemotherapy will be included for this trial: micropapillary, sarcomatoid and plasmacytoid features; 3-dimensional (3-D) mass on exam under anesthesia (EUA); lymphovascular invasion; hydronephrosis (unless in the opinion of the treating physician, this is not due to tumor); high grade (grade 3) tumors of the ureter, renal pelvis, or tumors in these areas with radiographic abnormality large enough to recognize as an abnormal mass by computed tomography (CT) or magnetic resonance imaging (MRI) imaging; direct invasion of the prostatic stroma or the vaginal wall (i.e. cT4a disease); patients who are candidates for but refusing conventional chemotherapy may be considered eligible; for patients in whom eligibility is unclear, final arbitration will be determined by the principal investigator
    • Subjects must have no prior exposure to immunotherapy, such as, but not limited to other anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies excluding vaccines
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
    • Able and willing to give valid written consent for available archival tumor samples or fresh tumor biopsies/resections
    • Adequate organ and marrow function (subjects must not have received transfusions or growth factor support within 28 days prior to first dose)
    • Hemoglobin >= 9 g/dL
    • Absolute neutrophil count >= 1,000/mm^3
    • Platelet count >= 100,000/mm^3
    • Total bilirubin =< 1.5 x upper limit of normal (ULN) except subjects with documented Gilbert's syndrome (> 3 x ULN), who must have a baseline total bilirubin =< 3.0 mg/dL
    • Subjects must be considered cisplatin ineligible as per treating physician due to renal dysfunction, or hearing impairment, or co-morbidities; cisplatin ineligibility defined as: glomerular filtration rate (GFR) less than 60 or; congestive heart failure (CHF) New York Heart Association (NYHA) class III or higher or; peripheral neuropathy grade 2 or higher or; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 or higher or; impaired hearing; patient's refusal of traditional chemotherapy
    • Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from the time of screening, and must agree to continue using such precautions for 180 days after the final dose of investigational product; cessation of contraception after this point should be discussed with a responsible physician; periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception; they must also refrain from egg cell donation for 180 days after the final dose of investigational product
    • Nonsterilized males who are sexually active with a female partner of childbearing potential must agree to use a highly effective method of contraception from day 1 through 90 days after receipt of the final dose of investigational product; in addition, they must refrain from sperm donation for 90 days after the final dose of investigational product
    • Mild autoimmune conditions (such as localized psoriasis) requiring minimal treatment or systemic autoimmune conditions well controlled by target agents such as an anti-IL-17 that do not affect overall immune system; patients with a history of Hashimoto's thyroiditis only requiring hormone replacement, type I diabetes, or conditions not expected to recur in the absence of an external trigger are allowed to participate

    Exclusion Criteria:

    • Concurrent enrollment in another clinical trial, unless in a follow-up period or it is an observational study
    • Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment; concurrent use of hormones for non-cancer-related conditions (e.g. insulin for diabetes and hormone replacement therapy) is acceptable
    • Any investigational anticancer therapy received within 28 days prior to the first dose of durvalumab and tremelimumab
    • Major surgical procedure (as defined by the principal investigator [PI] or co-PIs within 28 days prior to the first dose of durvalumab and tremelimumab or still recovering from prior surgery
    • Unresolved toxicities from prior anticancer therapy, defined as having not resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03 grade 0 or 1 with the exception of alopecia and laboratory values listed per the inclusion criteria; subjects with irreversible toxicity that is not reasonably expected to be exacerbated by durvalumab and tremelimumab may be included (e.g. hearing loss) after consultation with the principal investigator
    • Known or suspected autoimmune disease; patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus or autoimmune vasculitis (e.g., Wegener's granulomatosis) are excluded from this study; patients with a history of Hashimoto's thyroiditis only requiring hormone replacement, type I diabetes, or psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are allowed to participate; any condition requiring systemic treatment with corticosteroids (> 10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug; inhaled steroids and adrenal replacement steroids doses > 10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
    • History of primary immunodeficiency
    • Patients who have organ allografts
    • True active infections of hepatitis B, or C during screening
    • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
    • Receipt of live, attenuated vaccine within 28 days prior to the first dose of durvalumab and tremelimumab (NOTE: subjects, if enrolled, should not receive live vaccine during the study and for 180 days after the last dose of both drugs)
    • Females who are pregnant, lactating, or intend to become pregnant during their participation in the study
    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
    • Other invasive malignancies within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin, or ductal carcinoma in situ of the breast, etc. that has/have been surgically cured
    • Any evidence of metastatic urothelial carcinoma
    • Known allergy or hypersensitivity to study drug formulations
    • Patient currently on dialysis

    Contact:

    • Jianjun Gao
    • 713-792-2830

    Location:

    • M D Anderson Cancer Center
    • Houston Texas 77030 United States

    View trial on ClinicalTrials.gov


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    Published October 25, 2017
  • A Pilot Safety Study and Single Arm Phase II Study of Gemcitabine and Cisplatin With Atezolizumab (MPDL3280A) in Patients With Metastatic and Muscle Invasive Bladder Cancer, Respectively

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    A Pilot Safety Study and Single Arm Phase II Study of Gemcitabine and Cisplatin With Atezolizumab (MPDL3280A) in Patients With Metastatic and Muscle Invasive Bladder Cancer, Respectively


    Condition: Bladder Cancer, Metastatic Bladder Cancer, Urothelial Carcinoma

    Intervention:

    • Drug: Atezolizumab
    • Drug: Gemcitabine
    • Drug: Cisplatin

    Purpose: The purpose of this study is to test the safety of the study drug, atezolizumab, when combined with the standard chemotherapy drugs, gemcitabine and cisplatin (or GC). This study will help researchers begin to understand whether combining GC with atezolizumab is better, the same, or worse than the usual approach of using GC alone.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02989584

    Sponsor: Memorial Sloan Kettering Cancer Center

    Primary Outcome Measures:

    • Measure: Test the safety of atezolizumab in combination with gemcitabine/cisplatin as assessed by dose limiting toxicity rate.
    • Time Frame: Participants will be followed for survival until 5 years from treatment completion or until disease recurrence/progression.
    • Safety Issue:

    Estimated Enrollment: 30

    Study Start Date: December 20, 2016

    Phase: Phase 1/Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Age ≥ 18 years
    • ECOG Performance Status of 0 or 1
    • Required Initial Laboratory Values within 14 days of enrollment:
    • Absolute Neutrophil Count ≥ 1500 cells/mm^3
    • Lymphocyte count ≥ 300/mm^3
    • Platelets ≥ 100,000 cells/mm^3
    • Hemoglobin ≥ 9.0 g/dL
    • Bilirubin ≤ 1.5 the upper limit of normal (ULN) for the institution For patients with known Gilbert's disease: bilirubin ≤ 3 x ULN
    • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN for the institution.
    • For patients in the metastatic cohort with documented liver or bone metastases: AST and/or ALT ≤ 5.0 x ULN
    • Alkaline phosphatase ≤ 2.5 x ULN for the institution
    • For patients in the metastatic cohort with documented liver or bone metastases: alkaline phosphatase ≤ 5 x ULN
    • If female of childbearing potential, urine pregnancy test is negative.
    • INR and aPTT ≤ 1.5 x ULN if not on therapeutic anticoagulation. Patients receiving therapeutic anticoagulation should be on a stable dose. Phase I Cohort
    • Archival tumor specimens must be submitted prior to enrollment. Samples collected from fine-needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, and lavage are not acceptable. Acceptable samples include core-needle biopsies for deep tumor tissue (minimum of three cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. If archival tissue is being used, representative urothelial carcinoma FFPE tumor specimens (tumor blocks or 30 unstained slides) must be provided. Patients with < 30 slides may be enrolled after discussion with the principal investigator. Primary or metastatic specimens may be submitted.
    • Subject must agree to undergo two research-directed biopsies during treatment.
    • The patient must have measurable disease according to RECIST v1.1 and must have one site amenable to biopsy that, in the opinion of the investigator and/or interventional radiologist, is likely to yield acceptable tumor sample for a core biopsy per the above pathology criteria.
    • Life expectancy ≥ 12 weeks
    • Histologically or cytologically confirmed urothelial carcinoma (confirmed at the enrolling institution) of the bladder, ureter, urethra, or renal pelvis. Patients with mixed histologies are required to have a predominant urothelial component as reviewed by the pathologist at the treating institution.
    • Locally advanced (T4b, any N; any T, N2-3) or metastatic (M1) disease as determined by the treating investigator
    • Estimated glomerular filtration rate ≥ 60 ml/min/1.73m2 using the CKD- EPI equation: eGFR = 141 x min(Scr/k, 1)a x max(Scr/k, 1)-1.209 x 0.993Age°x 1.018 [if female] x 1.159 [if black] Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1 Phase 2 Cohort
    • Pathology: Representative urothelial carcinoma FFPE tumor specimens (tumor blocks or 30 unstained slides). Patients with < 30 slides may be enrolled after discussion with the principal investigator.
    • Muscle invasive urothelial carcinoma of the bladder histologically confirmed at the enrolling institution. (Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed provided the extent of disease is confirmed via imaging and/or EUA.)
    • Clinical stage T2-4a;N0/X;M0
    • Medically appropriate candidate for radical cystectomy, as per MSK or participating site Attending Urologic Oncologist
    • Estimated glomerular filtration rate ≥ 60 ml/min/1.73m2 using the CKD- EPI equation: eGFR = 141 x min(Scr/k, 1)a x max(Scr/k, 1)-1.209 x 0.993Age°x 1.018 [if female] x 1.159 [if black] Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1 Exclusion Criteria:
    • Evidence of NYHA functional class III or IV heart disease
    • Serious intercurrent medical or psychiatric illness, including serious active infection
    • Preexisting sensory grade ≥ 2 neuropathy
    • Preexisting grade ≥ 2 hearing loss
    • Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study. Transurethral resection or other urinary tract diagnostic procedures, excisional biopsy, or MediPort placement, are NOT defined as major surgical procedures.
    • Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
    • Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.0 grade ≥ 2. However, stable atrial fibrillation controlled medically or with a device (e.g. pacemaker) or prior ablation is allowed.
    • History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness
    • Concurrent treatment on another clinical trial; supportive care trials or non-treatment trials, e.g. QOL, are allowed
    • Pregnancy, lactation, or breast-feeding. Patients must be surgically sterile, postmenopausal, or must agree to use effective contraception during the period of therapy and for 5 months after the last dose of atezolizumab. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Male patients must be surgically sterile or agree to use effective contraception. Male patients will be encouraged to notify the study team if their female partner becomes pregnant while on study.
    • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, systemic vasculitis, or glomerulonephritis.
    • Patients with history of autoimmune related hypothyroidism on stable dose of thyroid replacement hormone may be eligible for this study
    • Patients with controlled Type I diabetes mellitus on a stable dose of insulin may be eligible for this study
    • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
    • History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
    • Patients with active hepatitis B virus (HBV, chronic or acute, defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C antibody
    • Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBc Ab] and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1 and confirmed to be negative.
    • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
    • Active tuberculosis or BCG infection
    • Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
    • Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1. Abnormal urinalysis does not constitute signs/symptoms of infection unless urine culture obtained at screening grows ≥ 100,000 colonies of bacteria. Patients with an ileal conduit and a urinalysis and/or culture that are abnormal are eligible unless they have peripheral blood WBC > ULN, fever, or other symptoms suggestive of a urinary tract infection.
    • Therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1
    • Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible.
    • Prior allogeneic stem cell or solid organ transplant
    • Administration of intravesical bacillus Calmette-Guerin (BCG) within 4 weeks before Cycle 1, Day 1
    • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study.
    • Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist ®) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study.
    • AEs from prior anticancer therapy that have not resolved to Grade ≤ 1 except for alopecia
    • Bisphosphonate therapy for symptomatic hypercalcemia
    • Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed.
    • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; and inherited liver disease
    • Patients with a history of or active bone marrow disorders expected to interfere with study therapy (e.g. acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma)
    • Known primary central nervous system (CNS) malignancy, active or untreated CNS metastases, symptomatic CNS metastases, and/or leptomeningeal disease
    • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
    • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
    • Rash must cover less than 10% of body surface area (BSA)
    • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
    • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
    • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
    • Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g. prostate cancer with Gleason score ≤ 6, and prostate-specific antigen [PSA] 10 mg/mL, etc). Medication-Related

    Exclusion Criteria:

    • Evidence of NYHA functional class III or IV heart disease
    • Serious intercurrent medical or psychiatric illness, including serious active infection
    • Preexisting sensory grade ≥ 2 neuropathy
    • Preexisting grade ≥ 2 hearing loss
    • Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study. Transurethral resection or other urinary tract diagnostic procedures, excisional biopsy, or MediPort placement, are NOT defined as major surgical procedures.
    • Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
    • Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.0 grade ≥ 2. However, stable atrial fibrillation controlled medically or with a device (e.g. pacemaker) or prior ablation is allowed.
    • History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness
    • Concurrent treatment on another clinical trial; supportive care trials or non-treatment trials, e.g. QOL, are allowed
    • Pregnancy, lactation, or breast-feeding. Patients must be surgically sterile, postmenopausal, or must agree to use effective contraception during the period of therapy and for 5 months after the last dose of atezolizumab. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Male patients must be surgically sterile or agree to use effective contraception. Male patients will be encouraged to notify the study team if their female partner becomes pregnant while on study.
    • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, systemic vasculitis, or glomerulonephritis.
    • Patients with history of autoimmune related hypothyroidism on stable dose of thyroid replacement hormone may be eligible for this study
    • Patients with controlled Type I diabetes mellitus on a stable dose of insulin may be eligible for this study
    • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
    • History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
    • Patients with active hepatitis B virus (HBV, chronic or acute, defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C antibody
    • Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBc Ab] and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1 and confirmed to be negative.
    • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
    • Active tuberculosis or BCG infection
    • Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
    • Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1. Abnormal urinalysis does not constitute signs/symptoms of infection unless urine culture obtained at screening grows ≥ 100,000 colonies of bacteria. Patients with an ileal conduit and a urinalysis and/or culture that are abnormal are eligible unless they have peripheral blood WBC > ULN, fever, or other symptoms suggestive of a urinary tract infection.
    • Therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1
    • Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible.
    • Prior allogeneic stem cell or solid organ transplant
    • Administration of intravesical bacillus Calmette-Guerin (BCG) within 4 weeks before Cycle 1, Day 1
    • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study.
    • Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist ®) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study.
    • AEs from prior anticancer therapy that have not resolved to Grade ≤ 1 except for alopecia
    • Bisphosphonate therapy for symptomatic hypercalcemia
    • Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed.
    • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; and inherited liver disease
    • Patients with a history of or active bone marrow disorders expected to interfere with study therapy (e.g. acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma)
    • Known primary central nervous system (CNS) malignancy, active or untreated CNS metastases, symptomatic CNS metastases, and/or leptomeningeal disease
    • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
    • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
    • Rash must cover less than 10% of body surface area (BSA)
    • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
    • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
    • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
    • Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g. prostate cancer with Gleason score ≤ 6, and prostate-specific antigen [PSA] 10 mg/mL, etc). Medication-Related Exclusion Criteria:
    • Prior treatment with anti-PD-1, and CTLA-4, or anti-a PD-L1 therapeutic antibody or pathway-targeting agents
    • Treatment with systemic immunostimulatory agents (including but not limited to interferon [IFN]-a or interleukin [IL]-2) within 6 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1
    • Concomitant use of another investigational agent and/or treatment with an investigational agent within 4 weeks prior to Cycle 1, Day 1 (or within five half-lives of the investigational product, whichever is longer)
    • Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1
    • Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled.
    • The use of inhaled corticosteroids or mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
    • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    • Known hypersensitivity to Chinese hamster ovary cell products or any component of the atezolizumab formulation Phase I Cohort
    • Prior chemotherapy or immunotherapy for metastatic urothelial bladder cancer. Prior neoadjuvant or adjuvant chemotherapy with first progression > 12 months is allowed.
    • Any approved anti-cancer therapy within 3 weeks prior to enrollment with the following exceptions:
    • Palliative radiotherapy for bone metastases must be completed > 7 days prior to baseline imaging and > 21 days prior to cycle 1 day 1 of treatment.
    • Hormone replacement therapy or oral contraceptives are permitted
    • Administration of intravesical bacillus Calmette-Guerin (BCG) >4 weeks before Cycle 1, Day 1 is allowed
    • Tumor-related pain increased above baseline for 2 weeks and not controlled by a stable dose of opiates
    • Uncontrolled pleural effusion, pericardial effusion, or ascites (indwelling drainage catheters allowed) Phase 2 Cohort
    • Prior systemic chemotherapy (prior intravesical therapy is allowed)
    • Prior radiation therapy to the bladder
    • Any approved anti-cancer therapy within 3 weeks prior to enrollment
    • Administration of intravesical bacillus Calmette-Guerin (BCG) >4 weeks before Cycle 1, Day 1 is allowed

    Contact:

    • Samuel Funt, MD
    • 646-422-4558

    Locations:

    • Hartford Healthcare Cancer Institute @ Hartford Hospital
    • Hartford Connecticut 06102 United States
    • Memoral Sloan Kettering Basking Ridge
    • Basking Ridge New Jersey United States
    • Memorial Sloan Kettering Bergen
    • Montvale New Jersey 07645 United States
    • Memorial Sloan Kettering Commack
    • Commack New York 11725 United States
    • Memoral Sloan Kettering Westchester
    • Harrison New York 10604 United States
    • New York University
    • New York New York 10010 United States
    • Memorial Sloan Kettering Cancer Center
    • New York New York 10065 United States
    • Memorial Sloan Kettering Rockville
    • Rockville Centre New York 11570 United States
    • Memorial Sloan Kettering Nassau
    • Uniondale New York 11553 United States
    • Ohio State University
    • Columbus Ohio 43210 United States
    • Lehigh Valley Health Network
    • Allentown Pennsylvania 18103 United States

    View trial on ClinicalTrials.gov


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    Published October 9, 2017
  • A Pilot Study to Evaluate the Safety of Neoadjuvant Nivolumab Alone or in Combination With Ipilimumab for Cisplatin-Ineligible Patients With Muscle Invasive Bladder Cancer (CA209-9DJ)

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    A Pilot Study to Evaluate the Safety of Neoadjuvant Nivolumab Alone or in Combination With Ipilimumab for Cisplatin-Ineligible Patients With Muscle Invasive Bladder Cancer (CA209-9DJ)


    Condition: Bladder Cancer

    Intervention:

    • Drug: Nivolumab
    • Drug: Ipilimumab
    • Procedure: Radical cystectomy

    Purpose: The purpose of this study is to test if immunotherapy with nivolumab alone or in combination with ipilimumab is safe and does not delay the planned bladder cancer surgery. The investigators want to see if treatment with these drugs prior to surgery may decrease the size of the bladder cancer and thus could help make the surgery more successful.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03520491

    Sponsor: Memorial Sloan Kettering Cancer Center

    Primary Outcome Measures:

    • Measure: number of patients who proceed to radical cystectomy and pelvic lymph node dissection
    • Time Frame: within 60 days after completion of neoadjuvant nivolumab or nivolumab in combination with ipilimumab for cisplatin-ineligible MIBC, without delays due to treatment-related toxicities or progressive disease
    • Safety Issue:

    Estimated Enrollment: 45

    Study Start Date: April 25, 2018

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologically confirmed diagnosis of urothelial carcinoma of the bladder. Variant histology is acceptable if there is a predominant urothelial component.
    • Cystoscopically and radiographically confirmed cT2-4a cN0 cM0 disease. Patients with cT4a disease invading into the prostatic stroma with no cystoscopic confirmation of muscle invasion are eligible.
    • Patients ineligible for cisplatin based on any of the following criteria:
    • Estimated or calculated creatinine clearance ≥ 30ml/min but < 60 ml/min
    • Grade 2 or above audiometric hearing loss (per CTCAE v4.0)
    • Grade 2 or above peripheral neuropathy (per CTCAE v4.0)
    • Availability of tumor specimen block or 30 unstained slides from diagnosis of muscle-invasive disease. Patients with fewer than 30 slides available may be enrolled after discussion with the Principal Investigator.
    • Karnofsky performance status ≥ 70%.
    • Medically appropriate candidate for radical cystectomy, as per MSK Attending Urologic Oncologist
    • Age ≥ 18 years.
    • Required initial laboratory values:
    • Absolute neutrophil count ≥ 1.5 x 10^9/L
    • Platelets ≥ 100 x 10^9/L
    • Bilirubin ≤1.5 times the upper limit of normal (x ULN)
    • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN
    • PTT/PT ≤1.5 x ULN or INR < 1.7 x ULN for patients who are not receiving therapeutic anticoagulation. Patients receiving therapeutic anticoagulation should be on a stable dose.

    Exclusion Criteria:

    • Prior treatment with systemic chemotherapy for bladder cancer. (Prior intravesical treatment is allowed.)
    • Prior bladder-directed radiotherapy.
    • Presence of active autoimmune disease, symptoms, or conditions, with the following exceptions: °Subjects with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skim disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, asymptomatic laboratory evidence of autoimmune disease (e.g.: +ANA, +RF, anti-thyroglobulin antibodies), or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
    • Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first dose of study drug. Inhaled or topical steroids, and adrenal replacement steroid doses are permitted in the absence of active autoimmune disease.
    • Unstable angina.
    • New York Heart Association (NYHA) Grade II or greater congestive heart failure.
    • History of myocardial infarction within 6 months.
    • History of stroke within 6 months.
    • Evidence of bleeding diathesis or coagulopathy. Therapeutic anticoagulation is permitted, but patients must be on a stable dose.
    • Major surgical procedure within 28 days prior to the study. (Transurethral resection of bladder tumor is permitted
    • Serious, non-healing wound, ulcer, or bone fracture.
    • Other prior malignancy active within the previous 2 years except for local or organ-confined early stage cancer that has been definitively treated with curative intent or does not require treatment, does not require ongoing treatment, has no evidence of active disease, and has a negligible risk of recurrence and is therefore unlikely to interfere with the endpoints of the study.
    • Subjects who have received prior therapy with any T cell co-stimulation or checkpoint pathways such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137; or other medicines specifically targeting T cells are prohibited. Prior IL-2 is permitted.
    • Prior therapy with intravesical BCG within 6 weeks of treatment.
    • Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection.
    • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
    • History of allergy to study drug component or history of severe hypersensitivity reaction to any monoclonal antibody.
    • Women who are breastfeeding or pregnant as evidenced by a positive pregnancy test within 14 days of first dose.
    • Male subjects who are unwilling to use contraception during the treatment and for at least 31 weeks after the last dose of study treatment (5 half-lives of study drug plus 90 days duration of sperm turnover).
    • Women of childbearing potential (WOCBP) not using a medically acceptable means of contraception throughout the study treatment and for at least 23 weeks following the last dose of study treatment (5 half-lives of study drug plus 30 days duration of ovulatory cycle).
    • WOCBP are defined as those who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post-menopausal is defined as:
    • Amenorrhea ≥ 12 consecutive months without another cause, or
    • For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
    • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
    • Inability to comply with study and/or follow-up procedures.

    Contact:

    • Min Yuen Teo, MD
    • 914-367-7393

    Locations:

    • Memoral Sloan Kettering Basking Ridge
    • Basking Ridge New Jersey 07920 United States
    • Memoral Sloan Kettering Monmouth
    • Middletown New Jersey 07748 United States
    • Memorial Sloan Kettering Bergen
    • Montvale New Jersey 07645 United States
    • Memorial Sloan Kettering Westchester
    • Harrison New York 10604 United States
    • Memorial Sloan Kettering Cancer Center
    • New York New York 10065 United States
    • Memorial Sloan Kettering Nassau
    • Uniondale New York 11553 United States

    View trial on ClinicalTrials.gov


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    Published September 25, 2018
  • A Randomised Phase II Trial of Adaptive Image Guided Standard or Dose Escalated Tumour Boost Radiotherapy in the Treatment of Transitional Cell Carcinoma of the Bladder

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    A Randomised Phase II Trial of Adaptive Image Guided Standard or Dose Escalated Tumour Boost Radiotherapy in the Treatment of Transitional Cell Carcinoma of the Bladder


    Condition: Bladder Cancer

    Intervention:

    • Radiation: WBRT
    • Radiation: SART
    • Radiation: DART

    Purpose: Bladder cancer is the seventh most common cancer in the UK, with 10,399 new cases diagnosed in 2011. In a quarter of these cases the cancer has infiltrated the muscular wall of the bladder (muscle invasive) and is life threatening. This type of bladder cancer is usually treated either with surgical removal of the bladder, or daily radiotherapy treatment (high strength xrays which kill cells), given every day for 4 or 7 weeks. RAIDER will investigate methods which have the potential to improve how well this radiotherapy works. RAIDER is based on a study of novel radiotherapy techniques which was conducted at a single UK NHS Trust. Bladder radiotherapy is normally delivered using a single plan throughout treatment and treats the whole bladder with the same radiotherapy dose. In adaptive radiotherapy the delivery plan is chosen from 3 possible plans. In cancer (tumour) focused radiotherapy, the highest dose of the radiotherapy is aimed at the tumour within the bladder. In RAIDER, 240 participants with muscle invasive bladder cancer will be in one of 3 treatment groups: 1. standard whole bladder radiotherapy 2. standard dose tumour focused adaptive radiotherapy 3. dose escalated tumour boost adaptive radiotherapy Participants will visit the hospital 4 weeks, 3, 6, 9, 12, 18 and 24 months after radiotherapy and annually thereafter to check whether the cancer has returned and to receive treatment for any symptoms they may be experiencing. RAIDER aims to confirm in a multicentre setting that novel techniques allow a higher radiotherapy dose than standard to be reliably targeted at the tumour within the bladder and to check that the long term side effects of the treatment are acceptable. If this is the case, results of RAIDER will be used to develop a study to establish whether dose escalated radiotherapy is better at treating bladder cancer than standard dose.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02447549

    Sponsor: Institute of Cancer Research, United Kingdom

    Primary Outcome Measures:

    • Measure: Proportion of participants meeting predefined radiotherapy dose constraints in DART group
    • Time Frame: 4-6 weeks from randomisation
    • Safety Issue:
    • Measure: Proportion of patients experiencing severe late side effects following radiotherapy.
    • Time Frame: 6-18 months post radiotherapy
    • Safety Issue:

    Estimated Enrollment: 240

    Study Start Date: September 2015

    Phase: Phase 2

    Eligibility:

    • Age: minimum 16 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Written informed consent
    • Age ≥16 years
    • Histologically or cytologically confirmed transitional cell carcinoma (TCC) of the bladder
    • Unifocal bladder TCC staged T2-T4a N0 M0
    • Fit to receive a radical course of radiotherapy
    • WHO performance status 0-2
    • Willing and able to comply with study procedures and follow up schedule

    Exclusion Criteria:

    • Nodal or metastatic disease
    • Widespread carcinoma in situ (CIS) or CIS remote from muscle invasive tumour or multifocal invasive disease
    • Simultaneous TCC in upper tract or urethra
    • Pregnancy
    • Active malignancy within 2 years of randomisation (not including non melanomatous skin carcinoma, previous non muscle invasive bladder tumours, NCCN low risk prostate cancer (T1/T2a, Gleason 6 PSA <10), in situ carcinoma of any site)
    • Any other conditions that in the Principal Investigator's opinion would be a contra-indication to radiotherapy (e.g. previous pelvic radiotherapy / inflammatory bowel disease)

    Contact:

    • RAIDER Trial Manager
    • 02087224295

    Locations:

    • Riverina Cancer Care Centre
    • Wagga Wagga New South Wales Australia
    • Princess Alexandra Hospital
    • Brisbane Queensland Australia
    • Townsville General Hospital
    • Douglas Queensland Australia
    • Radiation Oncology Mater Centre QLD
    • South Brisbane Queensland Australia
    • Royal Hobart Hospital
    • Hobart Tasmania Australia
    • Austin Hospital
    • Melbourne Victoria Australia
    • Sir Charles Gairdner Hospital
    • Nedlands Western Australia Australia
    • Auckland Hospital
    • Auckland New Zealand
    • Christchurch Hospital
    • Christchurch New Zealand
    • Waikato
    • Hamilton New Zealand
    • Tauranga
    • Tauranga New Zealand
    • Ipswich Hospital
    • Ipswich England IP4 5PD United Kingdom
    • Barts Health NHS Trust
    • London England EC1M 6BQ United Kingdom
    • The Christie NHS Foundation Trust
    • Manchester England M20 4BX United Kingdom
    • Nottingham University Hospital NHS Trust
    • Nottingham England NG5 1PB United Kingdom
    • Ayr Hospital
    • Ayr Scotland KA6 6DX United Kingdom
    • Maidstone Hospital, Kent Oncology Centre
    • Adstone United Kingdom
    • Belfast City Hospital
    • Belfast United Kingdom
    • Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust
    • Birmingham United Kingdom
    • Queen Elizabeth Hospital, University Hospitals Birmingham NHS Trust
    • Birmingham United Kingdom
    • Bradford Teaching Hospitals NHS Foundation Trust
    • Bradford United Kingdom
    • Royal Sussex County Hospital
    • Brighton United Kingdom
    • Bristol Haematology & Oncology Centre
    • Brixton United Kingdom
    • West Suffolk Hospital
    • Bury St Edmunds United Kingdom
    • Addenbrooke's Hospital
    • Cambridge United Kingdom
    • Velindre Hospital, Cardiff and Vale NHS Trust
    • Cardiff United Kingdom
    • Cheltenham General Hospital
    • Cheltenham United Kingdom
    • Cheltenham General Hospital
    • Cheltenham United Kingdom
    • University Hospital Coventry
    • Coventry United Kingdom
    • Western General Hospital
    • Edinburgh United Kingdom
    • Royal Devon and Exeter Hospital
    • Exeter United Kingdom
    • Beatson West of Scotland Cancer Centre
    • Glasgow United Kingdom
    • St Luke's Cancer Centre
    • Guildford United Kingdom
    • Leeds Teaching Hospitals NHS Trust
    • Leeds United Kingdom
    • Guy's and St Thomas' Hospital
    • London United Kingdom
    • Royal Marsden NHSFT
    • London United Kingdom
    • Royal Marsden NHSFT
    • London United Kingdom
    • University College London Hospital
    • London United Kingdom
    • Royal Oldham Hospital
    • Manchester United Kingdom
    • East Kent Hospitals University NHS Foundation Trust
    • Margate United Kingdom
    • Northern Centre for Cancer Care, Freeman Hospital,
    • Newcastle upon Tyne United Kingdom
    • Mount Vernon Cancer Centre
    • Northwood, Middlesex United Kingdom
    • Norfolk and Norwich University Hospital
    • Norwich United Kingdom
    • Peterborough City Hospital
    • Peterborough United Kingdom
    • Queen Alexandra Hospital
    • Portsmouth United Kingdom
    • Royal Preston Hospital
    • Preston United Kingdom
    • Queen's Hospital, Barking Havering and Redbridge University Hospitals NHS Trust
    • Romford, Essex United Kingdom
    • Weston Park Hospital, Sheffield Teaching Hospitals Trust
    • Sheffield United Kingdom
    • Southampton NHS Foundation Trust
    • Stadhampton United Kingdom
    • Kings Mill Hospital, Sherwood Forest Hospitals Foundation NHS Trust
    • Sutton-in-Ashfield United Kingdom
    • Musgrove Park Hospital, Taunton and Somerset NHS Foundation Trust
    • Taunton United Kingdom
    • Torbay District General Hospital
    • Torbay United Kingdom
    • Mid Yorkshire Hospitals
    • Wakefield United Kingdom
    • Pinderfields hospital, The Mid Yorkshire Hospitals NHS Trust
    • Wakefield United Kingdom
    • The Clatterbridge Cancer Centre NHS Foundation Trust
    • Wirral United Kingdom
    • The Royal Oldham Hospital
    • Yeldham United Kingdom

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • A Randomized Phase II Study of Co-Expression Extrapolation (COXEN) With Neoadjuvant Chemotherapy for Localized, Muscle-Invasive Bladder Cancer

    {{header-clinical-trials-navigation}}

    A Randomized Phase II Study of Co-Expression Extrapolation (COXEN) With Neoadjuvant Chemotherapy for Localized, Muscle-Invasive Bladder Cancer


    Condition: Bladder Cancer

    Intervention:

    • Drug: Gemcitabine
    • Drug: Cisplatin
    • Drug: Methotrexate
    • Drug: Vinblastine
    • Drug: Doxorubicin
    • Drug: Filgrastim

    Purpose: The primary focus of this study is to see if looking at tumor biomarkers using a program called coexpression extrapolation or "COXEN" may predict a patient's response to chemotherapy before surgery.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02177695

    Sponsor: Southwest Oncology Group

    Primary Outcome Measures:

    • Measure: The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores.
    • Time Frame: Up to 5 years
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Predictability of the CO-eXpression ExtrapolatioN (COXEN) score to direct which of the two regimens the patient should receive: gemcitabine+cisplatin (GC) versus dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: Overall survival
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: Pathologic T0 rate evaluation: gemcitabine+cisplatin (GC) versus dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
    • Time Frame: Up to 6 months
    • Safety Issue:

    Estimated Enrollment: 184

    Study Start Date: July 2014

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Histologically proven bladder cancer (pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma histologies are excluded).
    • Stage cT2-T4a N0 M0 disease.
    • Documented muscle invasive disease with at least one of the following: disease measuring at least 10 mm on cross-sectional imaging OR the presence of tumor-associated hydronephrosis.
    • Staging scans with abdominal/pelvic CT or MRI scan and CT scan or x-ray of the chest within 56 days prior to registration. If alkaline phosphatase is above the treating institution's upper limit of normal (ULN), presence of suspicious bone pain, or if other clinical suspicion, a whole body bone scan is required within 56 days prior to registration.
    • Performance status = 0 or 1
    • 18 years of age or older
    • Must have tumor tissue from transurethral resection of the bladder tumor (TURBT) available for submission that is sufficient for COXEN testing and must agree to submission of 20 (10 micron) slides plus 2 (5 micron) slides from the start and end of the 20 slides for a total of 22 unstained slides.
    • Must agree to collection of tissue (if residual disease is present), urine, and whole blood.
    • Must agree to participate in the translational medicine studies outlined in the protocol

    Exclusion Criteria:

    • Prior systemic cytotoxic chemotherapy or systemic anthracycline
    • Peripheral neuropathy >/= Grade 2
    • Class III/IV heart failure or known left ventricular ejection fraction (LVEF) < 50%
    • Clinically relevant hearing impairment > Grade 2
    • Renal function, calculated creatinine clearance < 60 mL/min
    • Hepatic function, total bilirubin > 1.5 x institutional upper limit of normal (IULN) (or > 2.5 x IULN with Gilbert's disease); AST & ALT > 2 X IULN
    • Hematologic function, absolute neutrophil count (ANC) < 1,500/mcL, hemoglobin < 9 g/dL, and platelets < 100,000/mcL
    • Hypersensitivity to cisplatin, gemcitabine, doxorubicin, vinblastine, methotrexate, or filgrastim/pegfilgrastim
    • Incidence of or uncontrolled medical illness (e.g. active cardiac symptoms, active systemic infection, etc.)
    • Pregnant or nursing females
    • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. However, patients with localized prostate cancer who are being followed by an active surveillance program are eligible.

    Contact:

    • Veronica Garcia
    • 210-614-8808 Ext. 1008

    Locations:

    • University of Alabama at Birmingham Cancer Center
    • Birmingham Alabama 35233 United States
    • Fairbanks Memorial Hospital
    • Fairbanks Alaska 99701 United States
    • University of Arizona Cancer Center at Saint Joseph's
    • Phoenix Arizona 85004 United States
    • University of Arizona Cancer Center-Orange Grove Campus
    • Tucson Arizona 85704 United States
    • University of Arizona Cancer Center-North Campus
    • Tucson Arizona 85719 United States
    • The University of Arizona Medical Center-University Campus
    • Tucson Arizona 85724 United States
    • Yuma Cancer Center
    • Yuma Arizona 85364 United States
    • Fowler Family Center for Cancer Care
    • Jonesboro Arkansas 72401 United States
    • AIS Cancer Center at San Joaquin Community Hospital
    • Bakersfield California 93301 United States
    • City of Hope Comprehensive Cancer Center
    • Duarte California 91010 United States
    • UC San Diego Moores Cancer Center
    • La Jolla California 92093 United States
    • City of Hope Antelope Valley
    • Lancaster California 93534 United States
    • Loma Linda University Medical Center
    • Loma Linda California 92354 United States
    • Los Angeles County-USC Medical Center
    • Los Angeles California 90033 United States
    • USC / Norris Comprehensive Cancer Center
    • Los Angeles California 90033 United States
    • Cedars Sinai Medical Center
    • Los Angeles California 90048 United States
    • Fremont - Rideout Cancer Center
    • Marysville California 95901 United States
    • USC Norris Oncology/Hematology-Newport Beach
    • Newport Beach California 92663 United States
    • Stanford Cancer Institute
    • Palo Alto California 94304 United States
    • PCR Oncology
    • Pismo Beach California 93449 United States
    • University of California Davis Comprehensive Cancer Center
    • Sacramento California 95817 United States
    • Stanford Cancer Center South Bay
    • San Jose California 95124 United States
    • City of Hope South Pasadena
    • South Pasadena California 91030 United States
    • Gene Upshaw Memorial Tahoe Forest Cancer Center
    • Truckee California 96161 United States
    • Rocky Mountain Cancer Centers-Aurora
    • Aurora Colorado 80012 United States
    • The Medical Center of Aurora
    • Aurora Colorado 80012 United States
    • University of Colorado Cancer Center - Anschutz Cancer Pavilion
    • Aurora Colorado 80045 United States
    • Boulder Community Hospital
    • Boulder Colorado 80301 United States
    • Rocky Mountain Cancer Centers-Boulder
    • Boulder Colorado 80304 United States
    • Penrose-Saint Francis Healthcare
    • Colorado Springs Colorado 80907 United States
    • Rocky Mountain Cancer Centers-Penrose
    • Colorado Springs Colorado 80907 United States
    • Memorial Hospital Central
    • Colorado Springs Colorado 80909 United States
    • Denver Health Medical Center
    • Denver Colorado 80204 United States
    • National Jewish Health-Main Campus
    • Denver Colorado 80206 United States
    • The Women's Imaging Center
    • Denver Colorado 80209 United States
    • Porter Adventist Hospital
    • Denver Colorado 80210 United States
    • Colorado Blood Cancer Institute
    • Denver Colorado 80218 United States
    • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver Colorado 80218 United States
    • Rocky Mountain Cancer Centers-Midtown
    • Denver Colorado 80218 United States
    • SCL Health Saint Joseph Hospital
    • Denver Colorado 80218 United States
    • Rocky Mountain Cancer Centers-Rose
    • Denver Colorado 80220 United States
    • Rose Medical Center
    • Denver Colorado 80220 United States
    • Colorado Cancer Research Program NCORP
    • Denver Colorado 80222 United States
    • Mercy Medical Center
    • Durango Colorado 81301 United States
    • Southwest Oncology PC
    • Durango Colorado 81301 United States
    • Comprehensive Cancer Care and Research Institute of Colorado LLC
    • Englewood Colorado 80113 United States
    • Swedish Medical Center
    • Englewood Colorado 80113 United States
    • Poudre Valley Hospital
    • Fort Collins Colorado 80524 United States
    • Mountain Blue Cancer Care Center
    • Golden Colorado 80401 United States
    • National Jewish Health-Western Hematology Oncology
    • Golden Colorado 80401 United States
    • Grand Valley Oncology
    • Grand Junction Colorado 81501 United States
    • North Colorado Medical Center
    • Greeley Colorado 80631 United States
    • Rocky Mountain Cancer Centers-Greenwood Village
    • Greenwood Village Colorado 80111 United States
    • Rocky Mountain Cancer Centers-Lakewood
    • Lakewood Colorado 80228 United States
    • Saint Anthony Hospital
    • Lakewood Colorado 80228 United States
    • Rocky Mountain Cancer Centers-Littleton
    • Littleton Colorado 80120 United States
    • Littleton Adventist Hospital
    • Littleton Colorado 80122 United States
    • Rocky Mountain Cancer Centers-Sky Ridge
    • Lone Tree Colorado 80124 United States
    • Sky Ridge Medical Center
    • Lone Tree Colorado 80124 United States
    • Longmont United Hospital
    • Longmont Colorado 80501 United States
    • Rocky Mountain Cancer Centers-Longmont
    • Longmont Colorado 80501 United States
    • McKee Medical Center
    • Loveland Colorado 80539 United States
    • Parker Adventist Hospital
    • Parker Colorado 80138 United States
    • Rocky Mountain Cancer Centers-Parker
    • Parker Colorado 80138 United States
    • Saint Mary Corwin Medical Center
    • Pueblo Colorado 81004 United States
    • Rocky Mountain Cancer Centers - Pueblo
    • Pueblo Colorado 81008 United States
    • Rocky Mountain Cancer Centers-Thornton
    • Thornton Colorado 80260 United States
    • SCL Health Lutheran Medical Center
    • Wheat Ridge Colorado 80033 United States
    • Greenwich Hospital
    • Greenwich Connecticut 06830 United States
    • Smilow Cancer Hospital Care Center at Saint Francis
    • Hartford Connecticut 06105 United States
    • Yale University
    • New Haven Connecticut 06520 United States
    • Beebe Medical Center
    • Lewes Delaware 19958 United States
    • Christiana Gynecologic Oncology LLC
    • Newark Delaware 19713 United States
    • Delaware Clinical and Laboratory Physicians PA
    • Newark Delaware 19713 United States
    • Helen F Graham Cancer Center
    • Newark Delaware 19713 United States
    • Medical Oncology Hematology Consultants PA
    • Newark Delaware 19713 United States
    • Regional Hematology and Oncology PA
    • Newark Delaware 19713 United States
    • Christiana Care Health System-Christiana Hospital
    • Newark Delaware 19718 United States
    • Beebe Health Campus
    • Rehoboth Beach Delaware 19971 United States
    • Nanticoke Memorial Hospital
    • Seaford Delaware 19973 United States
    • Christiana Care Health System-Wilmington Hospital
    • Wilmington Delaware 19801 United States
    • Sibley Memorial Hospital
    • Washington District of Columbia 20016 United States
    • Cleveland Clinic-Weston
    • Weston Florida 33331 United States
    • John B Amos Cancer Center
    • Columbus Georgia 31904 United States
    • Medical Center of Central Georgia
    • Macon Georgia 31201 United States
    • Hawaii Oncology Inc-Pali Momi
    • 'Aiea Hawaii 96701 United States
    • Pali Momi Medical Center
    • 'Aiea Hawaii 96701 United States
    • The Cancer Center of Hawaii-Leeward
    • 'Ewa Beach Hawaii 96706 United States
    • Hawaii Cancer Care Inc-POB II
    • Honolulu Hawaii 96813 United States
    • Hawaii Oncology Inc-POB I
    • Honolulu Hawaii 96813 United States
    • Island Urology
    • Honolulu Hawaii 96813 United States
    • Queen's Medical Center
    • Honolulu Hawaii 96813 United States
    • Straub Clinic and Hospital
    • Honolulu Hawaii 96813 United States
    • University of Hawaii Cancer Center
    • Honolulu Hawaii 96813 United States
    • Hawaii Cancer Care Inc-Liliha
    • Honolulu Hawaii 96817 United States
    • Hawaii Oncology Inc-Kuakini
    • Honolulu Hawaii 96817 United States
    • Kuakini Medical Center
    • Honolulu Hawaii 96817 United States
    • The Cancer Center of Hawaii-Liliha
    • Honolulu Hawaii 96817 United States
    • Kapiolani Medical Center for Women and Children
    • Honolulu Hawaii 96826 United States
    • Wilcox Memorial Hospital and Kauai Medical Clinic
    • Lihue Hawaii 96766 United States
    • Saint Alphonsus Cancer Care Center-Boise
    • Boise Idaho 83706 United States
    • Saint Alphonsus Cancer Care Center-Caldwell
    • Caldwell Idaho 83605 United States
    • Kootenai Medical Center
    • Coeur d'Alene Idaho 83814 United States
    • Walter Knox Memorial Hospital
    • Emmett Idaho 83617 United States
    • Idaho Urologic Institute-Meridian
    • Meridian Idaho 83642 United States
    • Saint Alphonsus Medical Center-Nampa
    • Nampa Idaho 83686 United States
    • Kootenai Cancer Center
    • Post Falls Idaho 83854 United States
    • Kootenai Cancer Clinic
    • Sandpoint Idaho 83864 United States
    • Saint Joseph Medical Center
    • Bloomington Illinois 61701 United States
    • Illinois CancerCare-Bloomington
    • Bloomington Illinois 61704 United States
    • Illinois CancerCare-Canton
    • Canton Illinois 61520 United States
    • Memorial Hospital of Carbondale
    • Carbondale Illinois 62902 United States
    • SIH Cancer Institute
    • Carterville Illinois 62918 United States
    • Illinois CancerCare-Carthage
    • Carthage Illinois 62321 United States
    • Centralia Oncology Clinic
    • Centralia Illinois 62801 United States
    • University of Chicago Comprehensive Cancer Center
    • Chicago Illinois 60637 United States
    • Cancer Care Center of Decatur
    • Decatur Illinois 62526 United States
    • Decatur Memorial Hospital
    • Decatur Illinois 62526 United States
    • Crossroads Cancer Center
    • Effingham Illinois 62401 United States
    • Illinois CancerCare-Eureka
    • Eureka Illinois 61530 United States
    • Illinois CancerCare-Galesburg
    • Galesburg Illinois 61401 United States
    • Western Illinois Cancer Treatment Center
    • Galesburg Illinois 61401 United States
    • Hines Veterans Administration Hospital
    • Hines Illinois 60141 United States
    • Illinois CancerCare-Kewanee Clinic
    • Kewanee Illinois 61443 United States
    • Illinois CancerCare-Macomb
    • Macomb Illinois 61455 United States
    • Loyola University Medical Center
    • Maywood Illinois 60153 United States
    • Good Samaritan Regional Health Center
    • Mount Vernon Illinois 62864 United States
    • UC Comprehensive Cancer Center at Silver Cross
    • New Lenox Illinois 60451 United States
    • University of Chicago Medicine-Orland Park
    • Orland Park Illinois 60462 United States
    • Illinois CancerCare-Ottawa Clinic
    • Ottawa Illinois 61350 United States
    • Radiation Oncology of Northern Illinois
    • Ottawa Illinois 61350 United States
    • Illinois CancerCare-Pekin
    • Pekin Illinois 61554 United States
    • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
    • Pekin Illinois 61554 United States
    • Methodist Medical Center of Illinois
    • Peoria Illinois 61603 United States
    • Illinois CancerCare-Peoria
    • Peoria Illinois 61615 United States
    • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
    • Peoria Illinois 61615 United States
    • OSF Saint Francis Medical Center
    • Peoria Illinois 61637 United States
    • Illinois CancerCare-Peru
    • Peru Illinois 61354 United States
    • Valley Radiation Oncology
    • Peru Illinois 61354 United States
    • Illinois CancerCare-Princeton
    • Princeton Illinois 61356 United States
    • Central Illinois Hematology Oncology Center
    • Springfield Illinois 62702 United States
    • Southern Illinois University School of Medicine
    • Springfield Illinois 62702 United States
    • Springfield Clinic
    • Springfield Illinois 62702 United States
    • Memorial Medical Center
    • Springfield Illinois 62781 United States
    • Cancer Care Specialists of Illinois-Swansea
    • Swansea Illinois 62226 United States
    • Memorial and Saint Elizabeth's Health Care Services LLP
    • Swansea Illinois 62226 United States
    • Reid Health
    • Richmond Indiana 47374 United States
    • University of Iowa/Holden Comprehensive Cancer Center
    • Iowa City Iowa 52242 United States
    • Siouxland Regional Cancer Center
    • Sioux City Iowa 51101 United States
    • Cancer Center of Kansas - Chanute
    • Chanute Kansas 66720 United States
    • Cancer Center of Kansas - Dodge City
    • Dodge City Kansas 67801 United States
    • Cancer Center of Kansas - El Dorado
    • El Dorado Kansas 67042 United States
    • Newman Regional Health
    • Emporia Kansas 66801 United States
    • Cancer Center of Kansas - Fort Scott
    • Fort Scott Kansas 66701 United States
    • Saint Catherine Hospital
    • Garden City Kansas 67846 United States
    • Heartland Cancer Center
    • Great Bend Kansas 67530 United States
    • Saint Rose Ambulatory and Surgery Center
    • Great Bend Kansas 67530 United States
    • Hays Medical Center
    • Hays Kansas 67601 United States
    • Cancer Center of Kansas-Independence
    • Independence Kansas 67301 United States
    • University of Kansas Cancer Center-West
    • Kansas City Kansas 66112 United States
    • University of Kansas Cancer Center
    • Kansas City Kansas 66160 United States
    • Cancer Center of Kansas-Kingman
    • Kingman Kansas 67068 United States
    • Lawrence Memorial Hospital
    • Lawrence Kansas 66044 United States
    • Kansas Institute of Medicine Cancer and Blood Center
    • Lenexa Kansas 66219 United States
    • Minimally Invasive Surgery Hospital
    • Lenexa Kansas 66219 United States
    • Cancer Center of Kansas-Liberal
    • Liberal Kansas 67905 United States
    • Cancer Center of Kansas-Manhattan
    • Manhattan Kansas 66502 United States
    • Cancer Center of Kansas - McPherson
    • McPherson Kansas 67460 United States
    • Cancer Center of Kansas - Newton
    • Newton Kansas 67114 United States
    • Olathe Medical Center
    • Olathe Kansas 66061 United States
    • Menorah Medical Center
    • Overland Park Kansas 66209 United States
    • University of Kansas Cancer Center-Overland Park
    • Overland Park Kansas 66210 United States
    • Saint Luke's South Hospital
    • Overland Park Kansas 66213 United States
    • Cancer Center of Kansas - Parsons
    • Parsons Kansas 67357 United States
    • Via Christi Hospital-Pittsburg
    • Pittsburg Kansas 66762 United States
    • Kansas City NCI Community Oncology Research Program
    • Prairie Village Kansas 66208 United States
    • Cancer Center of Kansas - Pratt
    • Pratt Kansas 67124 United States
    • Cancer Center of Kansas - Salina
    • Salina Kansas 67401 United States
    • Salina Regional Health Center
    • Salina Kansas 67401 United States
    • Saint Francis Hospital and Medical Center - Topeka
    • Topeka Kansas 66606 United States
    • Cancer Center of Kansas - Wellington
    • Wellington Kansas 67152 United States
    • Associates In Womens Health
    • Wichita Kansas 67208 United States
    • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita Kansas 67208 United States
    • Cancer Center of Kansas - Wichita
    • Wichita Kansas 67214 United States
    • Via Christi Regional Medical Center
    • Wichita Kansas 67214 United States
    • Wichita NCI Community Oncology Research Program
    • Wichita Kansas 67214 United States
    • Cancer Center of Kansas - Winfield
    • Winfield Kansas 67156 United States
    • LSU Health Baton Rouge-North Clinic
    • Baton Rouge Louisiana 70805 United States
    • Louisiana Hematology Oncology Associates LLC
    • Baton Rouge Louisiana 70809 United States
    • Mary Bird Perkins Cancer Center
    • Baton Rouge Louisiana 70809 United States
    • Medical Oncology LLC
    • Baton Rouge Louisiana 70809 United States
    • Mary Bird Cancer Center/Saint Tammany Parish
    • Covington Louisiana 70433 United States
    • North Shore Hematology Oncology Associates Inc
    • Covington Louisiana 70433 United States
    • Oncology Center of The South Incorporated
    • Houma Louisiana 70360 United States
    • East Jefferson General Hospital
    • Metairie Louisiana 70006 United States
    • Maine Center for Cancer Medicine-Scarborough
    • Scarborough Maine 04074 United States
    • Greater Baltimore Medical Center
    • Baltimore Maryland 21204 United States
    • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Baltimore Maryland 21287 United States
    • Hickman Cancer Center
    • Adrian Michigan 49221 United States
    • Saint Joseph Mercy Hospital
    • Ann Arbor Michigan 48106-0995 United States
    • University of Michigan Comprehensive Cancer Center
    • Ann Arbor Michigan 48109 United States
    • Bronson Battle Creek
    • Battle Creek Michigan 49017 United States
    • IHA Hematology Oncology Consultants-Brighton
    • Brighton Michigan 48114 United States
    • Saint Joseph Mercy Brighton
    • Brighton Michigan 48114 United States
    • Henry Ford Cancer Institute?Downriver
    • Brownstown Michigan 48183 United States
    • IHA Hematology Oncology Consultants-Canton
    • Canton Michigan 48188 United States
    • Saint Joseph Mercy Canton Health Center
    • Canton Michigan 48188 United States
    • Caro Cancer Center
    • Caro Michigan 48723 United States
    • IHA Hematology Oncology Consultants-Chelsea
    • Chelsea Michigan 48118 United States
    • Saint Joseph Mercy Chelsea
    • Chelsea Michigan 48118 United States
    • Hematology Oncology Consultants-Clarkston
    • Clarkston Michigan 48346 United States
    • Newland Medical Associates-Clarkston
    • Clarkston Michigan 48346 United States
    • Henry Ford Macomb Hospital-Clinton Township
    • Clinton Township Michigan 48038 United States
    • Beaumont Hospital-Dearborn
    • Dearborn Michigan 48124 United States
    • Henry Ford Medical Center-Fairlane
    • Dearborn Michigan 48126 United States
    • Wayne State University/Karmanos Cancer Institute
    • Detroit Michigan 48201 United States
    • Henry Ford Hospital
    • Detroit Michigan 48202 United States
    • Saint John Hospital and Medical Center
    • Detroit Michigan 48236 United States
    • Great Lakes Cancer Management Specialists-Doctors Park
    • East China Township Michigan 48054 United States
    • Green Bay Oncology - Escanaba
    • Escanaba Michigan 49829 United States
    • Weisberg Cancer Treatment Center
    • Farmington Hills Michigan 48334 United States
    • Botsford General Hospital
    • Farmington Michigan 48334 United States
    • Hurley Medical Center
    • Flint Michigan 48502 United States
    • Genesee Cancer and Blood Disease Treatment Center
    • Flint Michigan 48503 United States
    • Genesee Hematology Oncology PC
    • Flint Michigan 48503 United States
    • Genesys Hurley Cancer Institute
    • Flint Michigan 48503 United States
    • Mercy Health Saint Mary's
    • Grand Rapids Michigan 49503 United States
    • Spectrum Health at Butterworth Campus
    • Grand Rapids Michigan 49503 United States
    • Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
    • Grosse Pointe Woods Michigan 48236 United States
    • Lymphoma Clinic of Michigan
    • Grosse Pointe Woods Michigan 48236 United States
    • Michigan Breast Specialists-Grosse Pointe Woods
    • Grosse Pointe Woods Michigan 48236 United States
    • William Beaumont Hospital-Grosse Point
    • Grosse Pointe Michigan 48230 United States
    • Allegiance Health
    • Jackson Michigan 49201 United States
    • Borgess Medical Center
    • Kalamazoo Michigan 49001 United States
    • Bronson Methodist Hospital
    • Kalamazoo Michigan 49007 United States
    • West Michigan Cancer Center
    • Kalamazoo Michigan 49007 United States
    • Sparrow Hospital
    • Lansing Michigan 48912 United States
    • Hope Cancer Clinic
    • Livonia Michigan 48154 United States
    • Saint Mary Mercy Hospital
    • Livonia Michigan 48154 United States
    • Hematology Oncology Associates East PC
    • Macomb Michigan 48044 United States
    • Michigan Breast Specialists-Macomb Township
    • Macomb Michigan 48044 United States
    • Monroe Cancer Center
    • Monroe Michigan 48162 United States
    • Toledo Clinic Cancer Centers-Monroe
    • Monroe Michigan 48162 United States
    • Mercy Health Mercy Campus
    • Muskegon Michigan 49444 United States
    • Lakeland Community Hospital
    • Niles Michigan 49120 United States
    • Henry Ford Medical Center-Columbus
    • Novi Michigan 48377 United States
    • 21st Century Oncology-Pontiac
    • Pontiac Michigan 48341 United States
    • Hope Cancer Center
    • Pontiac Michigan 48341 United States
    • Newland Medical Associates-Pontiac
    • Pontiac Michigan 48341 United States
    • Saint Joseph Mercy Oakland
    • Pontiac Michigan 48341 United States
    • Lake Huron Medical Center
    • Port Huron Michigan 48060 United States
    • Spectrum Health Reed City Hospital
    • Reed City Michigan 49677 United States
    • Great Lakes Cancer Management Specialists-Rochester Hills
    • Rochester Hills Michigan 48309 United States
    • Michigan Cancer Specialists
    • Roseville Michigan 48066 United States
    • Oakland Colon and Rectal Association
    • Royal Oak Michigan 48067 United States
    • Cancer Care Associates PC
    • Royal Oak Michigan 48073 United States
    • Comprehensive Medical Center PLLC
    • Royal Oak Michigan 48073 United States
    • Hematology Oncology Consultants PC
    • Royal Oak Michigan 48073 United States
    • Oakland Medical Group
    • Royal Oak Michigan 48073 United States
    • William Beaumont Hospital-Royal Oak
    • Royal Oak Michigan 48073 United States
    • Saint Mary's of Michigan
    • Saginaw Michigan 48601 United States
    • Oncology Hematology Associates of Saginaw Valley PC
    • Saginaw Michigan 48604 United States
    • Lakeland Hospital
    • Saint Joseph Michigan 49085 United States
    • Marie Yeager Cancer Center
    • Saint Joseph Michigan 49085 United States
    • Bhadresh Nayak MD PC-Sterling Heights
    • Sterling Heights Michigan 48312 United States
    • Premier Hematology Oncology Care
    • Sterling Heights Michigan 48312 United States
    • Mitchell Folbe MD PC
    • Sterling Heights Michigan 48314 United States
    • Munson Medical Center
    • Traverse City Michigan 49684 United States
    • Michigan Institute of Urology-Town Center
    • Troy Michigan 48084 United States
    • Claudia BR Herke MD PC
    • Troy Michigan 48085 United States
    • Hematology Oncology Consultants PC-Troy
    • Troy Michigan 48098 United States
    • William Beaumont Hospital - Troy
    • Troy Michigan 48098 United States
    • Great Lakes Cancer Management Specialists-Macomb Professional Building
    • Warren Michigan 48093 United States
    • Macomb Hematology Oncology PC
    • Warren Michigan 48093 United States
    • Michigan Breast Specialists-Warren
    • Warren Michigan 48093 United States
    • Saint John Macomb-Oakland Hospital
    • Warren Michigan 48093 United States
    • Henry Ford West Bloomfield Hospital
    • West Bloomfield Michigan 48322 United States
    • Saint Mary's Oncology/Hematology Associates of West Branch
    • West Branch Michigan 48661 United States
    • Metro Health Hospital
    • Wyoming Michigan 49519 United States
    • Huron Gastroenterology PC
    • Ypsilanti Michigan 48106 United States
    • IHA Hematology Oncology Consultants-Ann Arbor
    • Ypsilanti Michigan 48197 United States
    • Essentia Health Saint Joseph's Medical Center
    • Brainerd Minnesota 56401 United States
    • Essentia Health Cancer Center
    • Duluth Minnesota 55805 United States
    • Essentia Health Saint Mary's Medical Center
    • Duluth Minnesota 55805 United States
    • Miller-Dwan Hospital
    • Duluth Minnesota 55805 United States
    • Lake Region Healthcare Corporation-Cancer Care
    • Fergus Falls Minnesota 56537 United States
    • Coborn Cancer Center at Saint Cloud Hospital
    • Saint Cloud Minnesota 56303 United States
    • Saint Cloud Hospital
    • Saint Cloud Minnesota 56303 United States
    • Central Care Cancer Center-Carrie J Babb Cancer Center
    • Bolivar Missouri 65613 United States
    • Parkland Health Center-Bonne Terre
    • Bonne Terre Missouri 63628 United States
    • CoxHealth Cancer Center
    • Branson Missouri 65616 United States
    • Saint Francis Medical Center
    • Cape Girardeau Missouri 63703 United States
    • Southeast Cancer Center
    • Cape Girardeau Missouri 63703 United States
    • Barnes-Jewish West County Hospital
    • Creve Coeur Missouri 63141 United States
    • Centerpoint Medical Center LLC
    • Independence Missouri 64057 United States
    • Capital Region Medical Center-Goldschmidt Cancer Center
    • Jefferson City Missouri 65109 United States
    • Freeman Health System
    • Joplin Missouri 64804 United States
    • Mercy Hospital-Joplin
    • Joplin Missouri 64804 United States
    • Truman Medical Center
    • Kansas City Missouri 64108 United States
    • Saint Luke's Hospital of Kansas City
    • Kansas City Missouri 64111 United States
    • Heartland Hematology and Oncology Associates Incorporated
    • Kansas City Missouri 64118 United States
    • Kansas City Veterans Affairs Medical Center
    • Kansas City Missouri 64128 United States
    • The University of Kansas Cancer Center-South
    • Kansas City Missouri 64131 United States
    • Research Medical Center
    • Kansas City Missouri 64132 United States
    • The University of Kansas Cancer Center-North
    • Kansas City Missouri 64154 United States
    • The University of Kansas Cancer Center-Lee's Summit
    • Lee's Summit Missouri 64064 United States
    • Saint Luke's East - Lee's Summit
    • Lee's Summit Missouri 64086 United States
    • Liberty Radiation Oncology Center
    • Liberty Missouri 64068 United States
    • Delbert Day Cancer Institute at PCRMC
    • Rolla Missouri 65401 United States
    • Saint John's Clinic-Rolla-Cancer and Hematology
    • Rolla Missouri 65401 United States
    • Heartland Regional Medical Center
    • Saint Joseph Missouri 64506 United States
    • Saint Louis Cancer and Breast Institute-South City
    • Saint Louis Missouri 63109 United States
    • Washington University School of Medicine
    • Saint Louis Missouri 63110 United States
    • Missouri Baptist Medical Center
    • Saint Louis Missouri 63131 United States
    • Mercy Hospital Saint Louis
    • Saint Louis Missouri 63141 United States
    • Siteman Cancer Center - Saint Peters
    • Saint Peters Missouri 63376 United States
    • Sainte Genevieve County Memorial Hospital
    • Sainte Genevieve Missouri 63670 United States
    • Mercy Hospital Springfield
    • Springfield Missouri 65804 United States
    • CoxHealth South Hospital
    • Springfield Missouri 65807 United States
    • Missouri Baptist Sullivan Hospital
    • Sullivan Missouri 63080 United States
    • Missouri Baptist Outpatient Center-Sunset Hills
    • Sunset Hills Missouri 63127 United States
    • Community Hospital of Anaconda
    • Anaconda Montana 59711 United States
    • Billings Clinic Cancer Center
    • Billings Montana 59101 United States
    • Saint Vincent Healthcare
    • Billings Montana 59101 United States
    • Montana Cancer Consortium NCORP
    • Billings Montana 59102 United States
    • Bozeman Deaconess Hospital
    • Bozeman Montana 59715 United States
    • Saint James Community Hospital and Cancer Treatment Center
    • Butte Montana 59701 United States
    • Benefis Healthcare- Sletten Cancer Institute
    • Great Falls Montana 59405 United States
    • Great Falls Clinic
    • Great Falls Montana 59405 United States
    • Saint Peter's Community Hospital
    • Helena Montana 59601 United States
    • Kalispell Regional Medical Center
    • Kalispell Montana 59901 United States
    • Saint Patrick Hospital - Community Hospital
    • Missoula Montana 59802 United States
    • Community Medical Hospital
    • Missoula Montana 59804 United States
    • University of Nebraska Medical Center
    • Omaha Nebraska 68198 United States
    • Carson Tahoe Regional Medical Center
    • Carson City Nevada 89703 United States
    • Cancer and Blood Specialists-Henderson
    • Henderson Nevada 89052 United States
    • Comprehensive Cancer Centers of Nevada - Henderson
    • Henderson Nevada 89052 United States
    • Las Vegas Cancer Center-Henderson
    • Henderson Nevada 89052 United States
    • 21st Century Oncology - Henderson
    • Henderson Nevada 89074 United States
    • Comprehensive Cancer Centers of Nevada-Southeast Henderson
    • Henderson Nevada 89074 United States
    • University Medical Center of Southern Nevada
    • Las Vegas Nevada 89102 United States
    • Cancer and Blood Specialists-Shadow
    • Las Vegas Nevada 89106 United States
    • Nevada Cancer Research Foundation CCOP
    • Las Vegas Nevada 89106 United States
    • Radiation Oncology Centers of Nevada Central
    • Las Vegas Nevada 89106 United States
    • 21st Century Oncology
    • Las Vegas Nevada 89109 United States
    • HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
    • Las Vegas Nevada 89109 United States
    • HealthCare Partners Medical Group Oncology/Hematology-San Martin
    • Las Vegas Nevada 89113 United States
    • Radiation Oncology Centers of Nevada Southeast
    • Las Vegas Nevada 89119 United States
    • Cancer Therapy and Integrative Medicine
    • Las Vegas Nevada 89121 United States
    • Ann M Wierman MD LTD
    • Las Vegas Nevada 89128 United States
    • Cancer and Blood Specialists-Tenaya
    • Las Vegas Nevada 89128 United States
    • Comprehensive Cancer Centers of Nevada - Northwest
    • Las Vegas Nevada 89128 United States
    • HealthCare Partners Medical Group Oncology/Hematology-Tenaya
    • Las Vegas Nevada 89128 United States
    • Comprehensive Cancer Centers of Nevada-Summerlin
    • Las Vegas Nevada 89144 United States
    • Summerlin Hospital Medical Center
    • Las Vegas Nevada 89144 United States
    • Las Vegas Cancer Center-Medical Center
    • Las Vegas Nevada 89148-2405 United States
    • 21st Century Oncology - Fort Apache
    • Las Vegas Nevada 89148 United States
    • Comprehensive Cancer Centers of Nevada
    • Las Vegas Nevada 89148 United States
    • Nevada Cancer Specialists-Fort Apache
    • Las Vegas Nevada 89148 United States
    • HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
    • Las Vegas Nevada 89149 United States
    • Comprehensive Cancer Centers of Nevada - Central Valley
    • Las Vegas Nevada 89169 United States
    • University Cancer Center
    • Las Vegas Nevada 89169 United States
    • 21st Century Oncology - Vegas Tenaya
    • Las Vegas Nevada 89182 United States
    • Renown Regional Medical Center
    • Reno Nevada 89502 United States
    • Saint Mary's Regional Medical Center
    • Reno Nevada 89503 United States
    • Inspira Medical Center Vineland
    • Vineland New Jersey 08360 United States
    • Inspira Medical Center Woodbury
    • Woodbury New Jersey 08096 United States
    • Montefiore Medical Center-Einstein Campus
    • Bronx New York 10461 United States
    • Montefiore Medical Center-Weiler Hospital
    • Bronx New York 10461 United States
    • Montefiore Medical Center - Moses Campus
    • Bronx New York 10467-2490 United States
    • Roswell Park Cancer Institute
    • Buffalo New York 14263 United States
    • Glens Falls Hospital
    • Glens Falls New York 12801 United States
    • Weill Medical College of Cornell University
    • New York New York 10065 United States
    • University of Rochester
    • Rochester New York 14642 United States
    • State University of New York Upstate Medical University
    • Syracuse New York 13210 United States
    • Asheville Hematology-Oncology Associates
    • Asheville North Carolina 28803 United States
    • UNC Lineberger Comprehensive Cancer Center
    • Chapel Hill North Carolina 27599 United States
    • Sampson Radiation Oncology
    • Clinton North Carolina 28328 United States
    • Southeastern Medical Oncology Center-Clinton
    • Clinton North Carolina 28328 United States
    • Southeastern Medical Oncology Center-Goldsboro
    • Goldsboro North Carolina 27534 United States
    • Wayne Memorial Hospital
    • Goldsboro North Carolina 27534 United States
    • Wayne Radiation Oncology
    • Goldsboro North Carolina 27534 United States
    • Park Ridge Hospital Breast Health Center
    • Hendersonville North Carolina 28792 United States
    • Onslow Memorial Hospital
    • Jacksonville North Carolina 28546 United States
    • Southeastern Medical Oncology Center-Jacksonville
    • Jacksonville North Carolina 28546 United States
    • Kinston Medical Specialists PA
    • Kinston North Carolina 28501 United States
    • Southeastern Medical Oncology Center-Wilson
    • Wilson North Carolina 27893 United States
    • Wake Forest University Health Sciences
    • Winston-Salem North Carolina 27157 United States
    • Essentia Health Cancer Center-South University Clinic
    • Fargo North Dakota 58103 United States
    • Dayton Physicians LLC-Miami Valley South
    • Centerville Ohio 45459 United States
    • Miami Valley Hospital South
    • Centerville Ohio 45459 United States
    • Oncology Hematology Care Inc-Kenwood
    • Cincinnati Ohio 45236 United States
    • MetroHealth Medical Center
    • Cleveland Ohio 44109 United States
    • Cleveland Clinic Cancer Center/Fairview Hospital
    • Cleveland Ohio 44111 United States
    • Cleveland Clinic Foundation
    • Cleveland Ohio 44195 United States
    • Ohio State University Comprehensive Cancer Center
    • Columbus Ohio 43210 United States
    • Good Samaritan Hospital - Dayton
    • Dayton Ohio 45406 United States
    • Miami Valley Hospital
    • Dayton Ohio 45409 United States
    • Dayton Physicians LLC-Samaritan North
    • Dayton Ohio 45415 United States
    • Samaritan North Health Center
    • Dayton Ohio 45415 United States
    • Armes Family Cancer Center
    • Findlay Ohio 45840 United States
    • Blanchard Valley Hospital
    • Findlay Ohio 45840 United States
    • Orion Cancer Care
    • Findlay Ohio 45840 United States
    • Atrium Medical Center-Middletown Regional Hospital
    • Franklin Ohio 45005-1066 United States
    • Dayton Physicians LLC-Atrium
    • Franklin Ohio 45005 United States
    • Dayton Physicians LLC-Wayne
    • Greenville Ohio 45331 United States
    • Wayne Hospital
    • Greenville Ohio 45331 United States
    • Cleveland Clinic Cancer Center Independence
    • Independence Ohio 44131 United States
    • Greater Dayton Cancer Center
    • Kettering Ohio 45409 United States
    • First Dayton Cancer Care
    • Kettering Ohio 45420 United States
    • Kettering Medical Center
    • Kettering Ohio 45429 United States
    • Cleveland Clinic Cancer Center Mansfield
    • Mansfield Ohio 44906 United States
    • Toledo Clinic Cancer Centers-Maumee
    • Maumee Ohio 43537 United States
    • Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
    • Maumee Ohio 43537 United States
    • Hillcrest Hospital Cancer Center
    • Mayfield Heights Ohio 44124 United States
    • Dayton Physicians LLC-Signal Point
    • Middletown Ohio 45042 United States
    • Saint Charles Hospital
    • Oregon Ohio 43616 United States
    • Mercy Health Perrysburg Cancer Center
    • Perrysburg Ohio 43551 United States
    • North Coast Cancer Care
    • Sandusky Ohio 44870 United States
    • Dayton Physicians LLC-Wilson
    • Sidney Ohio 45365 United States
    • Springfield Regional Cancer Center
    • Springfield Ohio 45504 United States
    • Springfield Regional Medical Center
    • Springfield Ohio 45505 United States
    • Cleveland Clinic Cancer Center Strongsville
    • Strongsville Ohio 44136 United States
    • Flower Hospital
    • Sylvania Ohio 43560 United States
    • The Toledo Hospital/Toledo Children's Hospital
    • Toledo Ohio 43606 United States
    • University of Toledo
    • Toledo Ohio 43614 United States
    • Mercy Saint Anne Hospital
    • Toledo Ohio 43623 United States
    • Toledo Clinic Cancer Centers-Toledo
    • Toledo Ohio 43623 United States
    • Dayton Physicians LLC-Upper Valley
    • Troy Ohio 45373 United States
    • Upper Valley Medical Center
    • Troy Ohio 45373 United States
    • South Pointe Hospital
    • Warrensville Heights Ohio 44122 United States
    • Cleveland Clinic Wooster Family Health and Surgery Center
    • Wooster Ohio 44691 United States
    • University of Oklahoma Health Sciences Center
    • Oklahoma City Oklahoma 73104 United States
    • Oklahoma Cancer Specialists and Research Institute-Tulsa
    • Tulsa Oklahoma 74146 United States
    • Saint Alphonsus Medical Center-Baker City
    • Baker City Oregon 97814 United States
    • Saint Alphonsus Medical Center-Ontario
    • Ontario Oregon 97914 United States
    • Oregon Health and Science University
    • Portland Oregon 97239 United States
    • Lehigh Valley Hospital-Cedar Crest
    • Allentown Pennsylvania 18103 United States
    • UPMC-Heritage Valley Health System Beaver
    • Beaver Pennsylvania 15009 United States
    • Lehigh Valley Hospital - Muhlenberg
    • Bethlehem Pennsylvania 18017 United States
    • Christiana Care Health System-Concord Health Center
    • Chadds Ford Pennsylvania 19317 United States
    • Geisinger Medical Center
    • Danville Pennsylvania 17822 United States
    • UPMC Cancer Centers - Arnold Palmer Pavilion
    • Greensburg Pennsylvania 15601 United States
    • Geisinger Medical Center-Cancer Center Hazleton
    • Hazleton Pennsylvania 18201 United States
    • UPMC-Johnstown/John P. Murtha Regional Cancer Center
    • Johnstown Pennsylvania 15901 United States
    • Geisinger Medical Oncology-Lewisburg
    • Lewisburg Pennsylvania 17837 United States
    • Lewistown Hospital
    • Lewistown Pennsylvania 17044 United States
    • UPMC Cancer Center at UPMC McKeesport
    • McKeesport Pennsylvania 15132 United States
    • UPMC-Coraopolis/Heritage Valley Radiation Oncology
    • Moon Pennsylvania 15108 United States
    • University of Pennsylvania/Abramson Cancer Center
    • Philadelphia Pennsylvania 19104 United States
    • Thomas Jefferson University Hospital
    • Philadelphia Pennsylvania 19107 United States
    • UPMC-Magee Womens Hospital
    • Pittsburgh Pennsylvania 15213 United States
    • UPMC-Presbyterian Hospital
    • Pittsburgh Pennsylvania 15213 United States
    • UPMC-Saint Margaret
    • Pittsburgh Pennsylvania 15215 United States
    • University of Pittsburgh Cancer Institute (UPCI)
    • Pittsburgh Pennsylvania 15232 United States
    • UPMC-Shadyside Hospital
    • Pittsburgh Pennsylvania 15232 United States
    • UPMC Jefferson Regional Radiation Oncology
    • Pittsburgh Pennsylvania 15236 United States
    • UPMC-Passavant Hospital
    • Pittsburgh Pennsylvania 15237 United States
    • UPMC-Saint Clair Hospital Cancer Center
    • Pittsburgh Pennsylvania 15243 United States
    • Geisinger Medical Oncology-Pottsville
    • Pottsville Pennsylvania 17901 United States
    • Community Medical Center
    • Scranton Pennsylvania 18510 United States
    • Geisinger Medical Oncology-Selinsgrove
    • Selinsgrove Pennsylvania 17870 United States
    • UPMC Cancer Center at UPMC Northwest
    • Seneca Pennsylvania 16346 United States
    • Geisinger Medical Group
    • State College Pennsylvania 16801 United States
    • UPMC Uniontown Hospital Radiation Oncology
    • Uniontown Pennsylvania 15401 United States
    • UPMC Washington Hospital Radiation Oncology
    • Washington Pennsylvania 15301 United States
    • Geisinger Wyoming Valley/Henry Cancer Center
    • Wilkes-Barre Pennsylvania 18711 United States
    • Medical University of South Carolina
    • Charleston South Carolina 29425 United States
    • Greenville Health System Cancer Institute-Easley
    • Easley South Carolina 29640 United States
    • Saint Francis Hospital
    • Greenville South Carolina 29601 United States
    • Greenville Health System Cancer Institute-Andrews
    • Greenville South Carolina 29605 United States
    • Greenville Health System Cancer Institute-Butternut
    • Greenville South Carolina 29605 United States
    • Greenville Health System Cancer Institute-Faris
    • Greenville South Carolina 29605 United States
    • Greenville Memorial Hospital
    • Greenville South Carolina 29605 United States
    • Saint Francis Cancer Center
    • Greenville South Carolina 29607 United States
    • Greenville Health System Cancer Institute-Eastside
    • Greenville South Carolina 29615 United States
    • Greenville Health System Cancer Institute-Greer
    • Greer South Carolina 29650 United States
    • Greenville Health System Cancer Institute-Seneca
    • Seneca South Carolina 29672 United States
    • Greenville Health System Cancer Institute-Spartanburg
    • Spartanburg South Carolina 29307 United States
    • Wellmont Bristol Regional Medical Center
    • Bristol Tennessee 37620 United States
    • Vanderbilt-Ingram Cancer Center Cool Springs
    • Franklin Tennessee 37067 United States
    • Wellmont Medical Associates Oncology and Hematology-Johnson City
    • Johnson City Tennessee 37604 United States
    • Wellmont Holston Valley Hospital and Medical Center
    • Kingsport Tennessee 37660 United States
    • Wellmont Medical Associates Oncology and Hematology-Kingsport
    • Kingsport Tennessee 37660 United States
    • Vanderbilt Breast Center at One Hundred Oaks
    • Nashville Tennessee 37204 United States
    • Vanderbilt University/Ingram Cancer Center
    • Nashville Tennessee 37232 United States
    • UT Southwestern/Simmons Cancer Center-Dallas
    • Dallas Texas 75390 United States
    • Brooke Army Medical Center
    • Fort Sam Houston Texas 78234 United States
    • UT Southwestern/Simmons Cancer Center-Fort Worth
    • Fort Worth Texas 76104 United States
    • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
    • Houston Texas 77030 United States
    • Ben Taub General Hospital
    • Houston Texas 77030 United States
    • M D Anderson Cancer Center
    • Houston Texas 77030 United States
    • Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
    • San Antonio Texas 78229 United States
    • University Hospital
    • San Antonio Texas 78229 United States
    • University of Texas Health Science Center at San Antonio
    • San Antonio Texas 78229 United States
    • Farmington Health Center
    • Farmington Utah 84025 United States
    • Huntsman Cancer Institute/University of Utah
    • Salt Lake City Utah 84112 United States
    • South Jordan Health Center
    • South Jordan Utah 84009 United States
    • Central Vermont Medical Center/National Life Cancer Treatment
    • Berlin Vermont 05602 United States
    • University of Vermont Medical Center
    • Burlington Vermont 05401 United States
    • University of Vermont College of Medicine
    • Burlington Vermont 05405 United States
    • University of Virginia Cancer Center
    • Charlottesville Virginia 22908 United States
    • Southwest VA Regional Cancer Center
    • Norton Virginia 24273 United States
    • MultiCare Auburn Medical Center
    • Auburn Washington 98001 United States
    • Virginia Mason Bainbridge Island Medical Center
    • Bainbridge Island Washington 98110 United States
    • Overlake Hospital Medical Center
    • Bellevue Washington 98004 United States
    • Virginia Mason Federal Way Medical Center
    • Federal Way Washington 98002 United States
    • Tacoma/Valley Radiation Oncology Centers-Gig Harbor
    • Gig Harbor Washington 98332 United States
    • MultiCare Gig Harbor Medical Park
    • Gig Harbor Washington 98335 United States
    • Northwest Cancer Clinic
    • Kennewick Washington 99336 United States
    • Virginia Mason Lynnwood Medical Center
    • Lynnwood Washington 98036 United States
    • Jefferson Healthcare
    • Port Townsend Washington 98368 United States
    • Peninsula Cancer Center
    • Poulsbo Washington 98370 United States
    • MultiCare Good Samaritan Hospital
    • Puyallup Washington 98372 United States
    • Tacoma/Valley Radiation Oncology Centers-Puyallup
    • Puyallup Washington 98372 United States
    • Virginia Mason Medical Center
    • Seattle Washington 98101 United States
    • Tacoma/Valley Radiation Oncology Centers-Jackson Hall
    • Tacoma Washington 97405 United States
    • MultiCare Tacoma General Hospital
    • Tacoma Washington 98405 United States
    • Northwest NCI Community Oncology Research Program
    • Tacoma Washington 98405 United States
    • Tacoma/Valley Radiation Oncology Centers-Saint Joe's
    • Tacoma Washington 98405 United States
    • West Virginia University Charleston
    • Charleston West Virginia 25304 United States
    • Aurora Cancer Care-Southern Lakes VLCC
    • Burlington Wisconsin 53105 United States
    • Marshfield Clinic-Chippewa Center
    • Chippewa Falls Wisconsin 54729 United States
    • Marshfield Clinic Cancer Center at Sacred Heart
    • Eau Claire Wisconsin 54701 United States
    • Aurora Health Center-Fond du Lac
    • Fond Du Lac Wisconsin 54937 United States
    • Aurora Health Care Germantown Health Center
    • Germantown Wisconsin 53022 United States
    • Aurora Cancer Care-Grafton
    • Grafton Wisconsin 53024 United States
    • Green Bay Oncology at Saint Vincent Hospital
    • Green Bay Wisconsin 54301-3526 United States
    • Saint Vincent Hospital Cancer Center Green Bay
    • Green Bay Wisconsin 54301 United States
    • Green Bay Oncology Limited at Saint Mary's Hospital
    • Green Bay Wisconsin 54303 United States
    • Saint Vincent Hospital Cancer Center at Saint Mary's
    • Green Bay Wisconsin 54303 United States
    • Aurora BayCare Medical Center
    • Green Bay Wisconsin 54311 United States
    • Aurora Cancer Care-Kenosha South
    • Kenosha Wisconsin 53142 United States
    • Gundersen Lutheran Medical Center
    • La Crosse Wisconsin 54601 United States
    • Holy Family Memorial Hospital
    • Manitowoc Wisconsin 54221 United States
    • Aurora Bay Area Medical Group-Marinette
    • Marinette Wisconsin 54143 United States
    • Bay Area Medical Center
    • Marinette Wisconsin 54143 United States
    • Vince Lombardi Cancer Clinic-Marinette
    • Marinette Wisconsin 54143 United States
    • Marshfield Clinic
    • Marshfield Wisconsin 54449 United States
    • Aurora Cancer Care-Milwaukee
    • Milwaukee Wisconsin 53209 United States
    • Aurora Saint Luke's Medical Center
    • Milwaukee Wisconsin 53215 United States
    • Froedtert and the Medical College of Wisconsin
    • Milwaukee Wisconsin 53226 United States
    • Aurora Sinai Medical Center
    • Milwaukee Wisconsin 53233 United States
    • Marshfield Clinic-Minocqua Center
    • Minocqua Wisconsin 54548 United States
    • Green Bay Oncology - Oconto Falls
    • Oconto Falls Wisconsin 54154 United States
    • Vince Lombardi Cancer Clinic - Oshkosh
    • Oshkosh Wisconsin 54904 United States
    • Aurora Cancer Care-Racine
    • Racine Wisconsin 53406 United States
    • Lakeview Medical Center-Marshfield Clinic
    • Rice Lake Wisconsin 54868 United States
    • Marshfield Clinic-Rice Lake Center
    • Rice Lake Wisconsin 54868 United States
    • HSHS Saint Nicholas Hospital
    • Sheboygan Wisconsin 53081 United States
    • Vince Lombardi Cancer Clinic-Sheboygan
    • Sheboygan Wisconsin 53081 United States
    • Marshfield Clinic Cancer Care at Saint Michael's Hospital
    • Stevens Point Wisconsin 54481 United States
    • Marshfield Clinic Stevens Point Center
    • Stevens Point Wisconsin 54482 United States
    • Saint Vincent Hospital Cancer Center at Sturgeon Bay
    • Sturgeon Bay Wisconsin 54235-1495 United States
    • Green Bay Oncology - Sturgeon Bay
    • Sturgeon Bay Wisconsin 54235 United States
    • Aurora Medical Center in Summit
    • Summit Wisconsin 53066 United States
    • Vince Lombardi Cancer Clinic-Two Rivers
    • Two Rivers Wisconsin 54241 United States
    • Aurora Cancer Care-Waukesha
    • Waukesha Wisconsin 53188 United States
    • Marshfield Clinic-Wausau Center
    • Wausau Wisconsin 54401 United States
    • Aurora Cancer Care-Milwaukee West
    • Wauwatosa Wisconsin 53226 United States
    • Aurora West Allis Medical Center
    • West Allis Wisconsin 53227 United States
    • Marshfield Clinic - Weston Center
    • Weston Wisconsin 54476 United States
    • Marshfield Clinic - Wisconsin Rapids Center
    • Wisconsin Rapids Wisconsin 54494 United States
    • Cheyenne Regional Medical Center-West
    • Cheyenne Wyoming 82001 United States
    • Big Horn Basin Cancer Center
    • Cody Wyoming 82414 United States
    • Billings Clinic-Cody
    • Cody Wyoming 82414 United States
    • Welch Cancer Center
    • Sheridan Wyoming 82801 United States

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • A Randomized Phase II Trial Evaluating an Organ-conserving Strategy With Radiotherapy + CDDP + Gemcitabine vs Radiotherapy + CDDP in Muscle-infiltrative Bladder Cancer

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    A Randomized Phase II Trial Evaluating an Organ-conserving Strategy With Radiotherapy + CDDP + Gemcitabine vs Radiotherapy + CDDP in Muscle-infiltrative Bladder Cancer


    Condition: Infiltrating Bladder Urothelial Carcinoma

    Intervention:

    • Other: Radiation + cisplatin
    • Other: Radiation + cisplatin + gemcitabine

    Purpose: If radical cystectomy remains the standard of care for muscle invasive bladder cancer, consequences of this surgical procedure are often harsh. Over the past years, concurrent chemo-radiotherapy has imposed itself as an alternative treatment. Published data on concomitant radiochemotherapy (radiotherapy/cisplatin or radiotherapy/cisplatin/5-fluorouracil combinations) showed local control rates with bladder preservation at 5 years ranging from 40% to 65% according to the disease stage, and overall survival probabilities ranging from 40% to 50% at 5 years. In order to improve local and systemic prognosis, evaluation of other chemotherapy agents with higher radiosensitizing effect, such as gemcitabine, is justified. Gemcitabine possesses its own anti-cancer activities on urothelial diseases and has a synergetic activity with cisplatin. The investigators completed a monocenter phase I study combining radiotherapy, cisplatin, and twice-weekly gemcitabine, and determined a recommended dose of gemcitabine 25 mg/m². The objective of the present study is to evaluate the combination of radiotherapy + cisplatin + gemcitabine in terms of disease-free survival in non metastatic muscle invasive urothelial cancer patients.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT01495676

    Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle

    Primary Outcome Measures:

    • Measure: Disease-free survival
    • Time Frame: Two years after the end of the complete therapeutic sequence
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Overall survival
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: Acute and late toxicities
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: Quality of life
    • Time Frame: Up to 5 years
    • Safety Issue:
    • Measure: Correlation between lymphocyte apoptosis and severity of late toxicities.
    • Time Frame: Up to 5 years
    • Safety Issue:

    Estimated Enrollment: 108

    Study Start Date: September 2011

    Phase: Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • Muscle invasive urothelial cancer (front line or following the progression of a superficial tumor), pT2-pT3 stage without lymphatic impairment (N0) and without detectable metastases (M0). An optimal macroscopic resection (TURB) have to be performed
    • The proof of invasive tumor to the muscle should be brought by a transurethral resection under anaesthesia less than 8 weeks before or, in the absence, by superficial biopsies and formal imaging. Multiples biopsies in the bladder must also be performed.
    • Age ≥ 18 years
    • Life expectancy ≥ 6 months
    • Kanorfsky index ≥ 70 % (WHO 0, 1, 2)
    • Biological criteria: neutrophils ≥ 1500/mm3, Platelets ≥ 100 000/mm3, haemoglobin ≥ 10 g/dl, creatinine clearance > 60 ml/mn
    • No distant metastases (Thorax, abdomen, and pelvic CT-scan, bone scan)
    • Efficient contraception for premenopausal women, maintained during the whole treatment and up to two months after the completion of radiotherapy.
    • No radiotherapy or chemotherapy history except for in situ bladder lesions.
    • No carcinological history except for non melanoma skin tumours, in situ uterine cervix cancer
    • No contraindication to gemcitabine or cisplatin.
    • No contraindication to radiotherapy
    • Information letter and informed consent signed
    • Patient covered by social security

    Exclusion Criteria:

    • Bladder tumors without any muscle infiltration
    • Epidermoid carcinoma or adenocarcinoma
    • Distance metastases or extrapelvic node positivity
    • Severe digestive history (ulcerative colitis, complicated diverticulitis)
    • Pregnancy and breast feeding

    Contact:

    • David Azria, MD., Ph D
    • +33 4 67 61 31 35

    Location:

    • CRLC Val d'Aurelle-Paul Lamarque
    • Montpellier 34000 France

    View trial on ClinicalTrials.gov


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    Published January 25, 2017
  • Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Observation After Curative Intent Resection of Cholangiocarcinoma and Muscle Invasive Gall Bladder Carcinoma (ACTICCA-1 Trial)

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    Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Cholangiocarcinoma and Muscle Invasive Gall Bladder Carcinoma (ACTICCA-1 Trial)


    Condition: Cholangiocarcinoma, Gall Bladder Carcinoma

    Intervention:

    • Drug: Gemcitabine
    • Drug: Cisplatin
    • Drug: Capecitabine

    Purpose: This is a multicentre, two stage, prospective, randomized, controlled phase III trial designed to assess the clinical performance of gemcitabine with cisplatin and observation vs. standard of care (capecitabine) and observation in patients after curative intent resection of cholangiocarcinoma and muscle invasive gall bladder carcinoma.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02170090

    Sponsor: Universitätsklinikum Hamburg-Eppendorf

    Primary Outcome Measures:

    • Measure: Disease free survival (DFS)
    • Time Frame: Disease free survival rate at 24 months (DFSR@24)
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Disease free survival rate at 24 months (DFSR@24)
    • Time Frame: 24 months
    • Safety Issue:
    • Measure: Recurrence free survival
    • Time Frame: 24 months
    • Safety Issue:
    • Measure: Overall survival
    • Time Frame: 84 months
    • Safety Issue:
    • Measure: Safety and tolerability (assessed by the rate of patients with adverse events according to NCI CTC AE v4.03)
    • Time Frame: 24 months
    • Safety Issue:
    • Measure: Quality of life
    • Time Frame: 48 months
    • Safety Issue:
    • Measure: Function of biliodigestive anastomosis (in terms of surgical revision, requirement for PTCD)
    • Time Frame: 48 months
    • Safety Issue:
    • Measure: Rate and severity of biliary tract infections
    • Time Frame: 48 months
    • Safety Issue:
    • Measure: Patterns of disease recurrence
    • Time Frame: 48 months
    • Safety Issue:
    • Measure: locoregional control (assessed by the rate of patients with hepatic or locoregional recurrence)
    • Time Frame: 48 months
    • Safety Issue:

    Estimated Enrollment: 781

    Study Start Date: April 2014

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Criteria: All enrolled patients will postoperatively be assessed for eligibility for the treatment phase. Additionally patients not previously enrolled into the trial for whatever reason (e.g. incidental finding during surgery) will be evaluated for eligibility. - Histologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) after radical surgical therapy with macroscopically complete resection (mixed tumor entities (HCC/CCA) are excluded) - Macroscopically complete resection (R0/1) within 6 (-16) weeks before scheduled start of chemotherapy - ECOG 0-1 - Age ≥18 years - Adequate hematologic function - Adequate liver function - Adequate renal function - No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy - No concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization - Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women <1 year after the onset of menopause (Note: a negative test has to be reconfirmed by a urine test, should the 7-day window be exceeded) Criteria for initial study enrolment - Written informed consent - No prior chemotherapy for cholangiocarcinoma - No previous malignancy within 3 years or concomitant malignancy, except: non-melanomatous skin cancer or adequately treated in situ cervical cancer - No severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last 3 months, significant arrhythmia) - Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent - No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial - Fertile women (< 1 year after last menstruation) and procreative men willing and able to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) - No pregnancy or lactation

    Contact:

    • Alexander Stein
    • 004940741056882

    Locations:

    • Bankstown Hospital
    • Bankstown New South Wales Australia
    • Nepean Hospital Cancer Care
    • Kingswood New South Wales Australia
    • St. George Hospital
    • Kogarah New South Wales Australia
    • Prince of Wales Hospital
    • Randwick New South Wales Australia
    • Calvary Mater Newcastle
    • Waratah New South Wales Australia
    • Townsville Hospital
    • Douglas Queensland Australia
    • Royal Brisbane and Women's Hospital
    • Herston Queensland Australia
    • Princess Alexandra Hospital
    • Woolloongabba Queensland Australia
    • Flinders Medical Centre
    • Bedford Park South Australia Australia
    • Fiona Stanley Hospital Perth
    • Murdoch Western Australia 6150 Australia
    • Sir Charles Gairdner Hospital
    • Nedlands Western Australia Australia
    • St. John of God
    • Subiaco Western Australia 6008 Australia
    • Kaiser-Franz-Josef Hospital
    • Vienna 1030 Austria
    • Vejle Hospital
    • Vejle Denmark
    • University Medical Center Aachen
    • Aachen Germany
    • Charite Berlin
    • Berlin Germany
    • University Medical Center Carl Gustav Carus
    • Dresden Germany
    • University Medical Center Essen
    • Essen Germany
    • University of Frankfurt
    • Frankfurt Germany
    • University Medical Center Freiburg
    • Freiburg Germany
    • University Medical Center Hamburg-Eppendorf
    • Hamburg 20246 Germany
    • University of Hannover
    • Hannover Germany
    • University of Heidelberg
    • Heidelberg Germany
    • University of Saarland
    • Homburg Germany
    • University Medical Center Jena
    • Jena Germany
    • University Hospital Schleswig-Holstein Campus Kiel
    • Kiel Germany
    • Johannes Gutenberg University of Mainz
    • Mainz Germany
    • University of Mannheim
    • Mannheim Germany
    • University of Munich Grosshadern
    • Munich Germany
    • University of Regensburg
    • Regensburg Germany
    • University Medical Center Tuebingen
    • Tuebingen Germany
    • University of Ulm
    • Ulm Germany
    • University Medical Center
    • Wuerzburg Germany
    • Academic Medical Center
    • Amsterdam Netherlands
    • UMC Groningen Cancer Center
    • Groningen Netherlands
    • University Medical Center
    • Maastricht Netherlands
    • Erasmus Medisch Centrum
    • Rotterdam Netherlands
    • Universitair Medisch Centrum Utrecht
    • Utrecht Netherlands
    • Hampshire Hospitals NHS Foundation Trust
    • Basingstoke United Kingdom
    • Queen Elizabeth Hospital Birmingham
    • Birmingham United Kingdom
    • Royal Bournemouth Hospital
    • Bournemouth United Kingdom
    • Bristol Haematology and Oncology Centre
    • Bristol United Kingdom
    • Addenbrooke's Hospital Cambridge
    • Cambridge United Kingdom
    • Velindre Hospital Cardiff
    • Cardiff United Kingdom
    • Western General Hospital Edinburgh
    • Edinburgh United Kingdom
    • Beatson West of Scotland Cancer Centre Glasgow
    • Glasgow United Kingdom
    • James Paget University Hospitals
    • Great Yarmouth United Kingdom
    • Royal Surrey County Hospital Guildford
    • Guildford United Kingdom
    • Huddersfield Royal Infirmary
    • Huddersfield United Kingdom
    • St James's University Hospital Leeds
    • Leeds United Kingdom
    • Guy's and St Thomas's Hospital London
    • London United Kingdom
    • Hammersmith Hospital London
    • London United Kingdom
    • Royal Free Hospital London
    • London United Kingdom
    • St Bartholomew's Hospital London
    • London United Kingdom
    • University College London Hospital
    • London United Kingdom
    • Maidstone Hospital
    • Maidstone United Kingdom
    • Christie Hospital Manchester
    • Manchester United Kingdom
    • Freeman Hospital Newcastle
    • Newcastle United Kingdom
    • Nottingham University Hospitals NHS Trust
    • Nottingham United Kingdom
    • Churchill Hospital Oxford
    • Oxford United Kingdom
    • Derriford Hospital Plymouth
    • Plymouth United Kingdom
    • Weston Park Hospital Sheffield
    • Sheffield United Kingdom
    • Southampton General Hospital
    • Southampton United Kingdom
    • Clatterbridge Cancer Centre
    • Wirral United Kingdom

    View trial on ClinicalTrials.gov


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    Published June 29, 2017
  • Adjuvant Radiotherapy After Cystectomy for Patients With Muscle Invasive Bladder Cancer: a Phase II Trial.

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    Adjuvant Radiotherapy After Cystectomy for Patients With Muscle Invasive Bladder Cancer: a Phase II Trial.


    Condition: Toxicity

    Intervention:

    • Radiation: Adjuvant EBRT

    Purpose: A radical cystectomy + extended pelvic lymph node dissection is considered to be the treatment of choice for patients with muscle invasive bladder cancer (MIBC). Despite this aggressive treatment the outcome is poor and ultimately, 30% of the patients with ≥pT3 tumors develop a pelvic recurrence. One- and 2-years survival for patients developing a local recurrence after cystectomy is only 8% and 3% respectively, with a median survival of <4 months. For patients with lymph node recurrence prognosis is somewhat better, but nevertheless still disappointing with reported 1- and 2 years survival of 42% and 11% respectively. The investigators hypothesize that an earlier implementation of external beam radiotherapy (EBRT) i.e. in the adjuvant setting, will prevent local and lymph node recurrence and improve disease free- and overall survival as local recurrence is linked to the development of distant metastasis. Adjuvant EBRT was tested in a prospective randomized trial and resulted in a 20% increase in 5-year disease free survival. Despite those impressive results, severe intestinal toxicity rates hampered the enthusiasm to use adjuvant EBRT, till now. In the last decade, great technological advancements in EBRT planning, such as intensity modulated arc therapy (IMAT), and positioning have been realised. This has resulted in a better coverage of the target volume while sparing normal tissue (mainly small bowel) and in a more precise delivery of the EBRT. Therefore, it is desirable to reconsider the use of adjuvant EBRT in selected MIBC patients.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02397434

    Sponsor: University Hospital, Ghent

    Primary Outcome Measures:

    • Measure: change from baseline in acute Radiation Therapy Oncology Group (RTOG) toxicity
    • Time Frame: last day of radiotherapy, 1 month and 3 months after last day of EBRT
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: change from baseline in late RTOG toxicity
    • Time Frame: at 6,9, 12, 18 and 24months after last day of EBRT
    • Safety Issue:
    • Measure: change from baseline in local control
    • Time Frame: at 6,9, 12, 18 and 24months after last day of EBRT
    • Safety Issue:
    • Measure: disease free survival
    • Time Frame: at 6,9, 12, 18 and 24months after last day of EBRT
    • Safety Issue:
    • Measure: overall survival
    • Time Frame: at 6,9, 12, 18 and 24months after last day of EBRT
    • Safety Issue:

    Estimated Enrollment: 76

    Study Start Date: October 2014

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: All

    Inclusion Criteria:

    • muscle invasive bladder cancer with:
    • ≥ pathological tumor stage (p)T3 stage + presence of lymphovascular invasion on pathological examination
    • pT4
    • <10 lymph nodes removed
    • positive lymph nodes
    • positive surgical margins

    Exclusion Criteria:

      Contact:

      • Valérie Fonteyne, MD, PhD

      Location:

      • Dept of Radiotherapy, University Hospital Ghent
      • Ghent 9000 Belgium

      View trial on ClinicalTrials.gov


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      Published January 25, 2017
    1. An Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Multi-Centre, Multi-arm Phase 1b Study in Patients With Muscle Invasive Bladder Cancer (MIBC) Who Have Progressed on Prior Treatment (BISCAY)

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      An Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Multi-Centre, Multi-arm Phase 1b Study in Patients With Muscle Invasive Bladder Cancer (MIBC) Who Have Progressed on Prior Treatment (BISCAY).


      Condition: Muscle Invasive Bladder Cancer

      Intervention:

      • Drug: AZD4547
      • Drug: MEDI4736
      • Drug: Olaparib
      • Drug: AZD1775
      • Drug: Vistusertib
      • Drug: AZD9150
      • Drug: Selumetinib

      Purpose: This is an open label, multi-drug, biomarker-directed, multi-centre, multi-arm, Phase 1b study in patients with muscle invasive bladder cancer (MIBC) (urothelial) who have progressed on prior treatment. This study is modular in design, allowing evaluation of the safety, tolerability, pharmacokinetics and anti-tumour activity of multiple agents as monotherapy and as combinations of different novel anti-cancer agents. The study will consist of a number of study modules (sub-studies), each evaluating the safety and tolerability of a specific agent or combination.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02546661

      Sponsor: AstraZeneca

      Primary Outcome Measures:

      • Measure: Module A: The frequency and nature of adverse events related to AZD4547 monotherapy.
      • Time Frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
      • Safety Issue:
      • Measure: Module A: The frequency and nature of adverse events related to the combination of intravenous MEDI4736 (durvalumab) and oral AZD4547.
      • Time Frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
      • Safety Issue:
      • Measure: Module B: The frequency and nature of adverse events related to the combination of intravenous MEDI4736 (durvalumab) and oral olaparib.
      • Time Frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
      • Safety Issue:
      • Measure: Module C: The frequency and nature of adverse events related to intravenous MEDI4736 (durvalumab) when given in combination with oral AZD1775.
      • Time Frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
      • Safety Issue:
      • Measure: Module D: The frequency and nature of adverse events related to intravenous MEDI4736 (durvalumab) monotherapy.
      • Time Frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
      • Safety Issue:
      • Measure: Module E: The frequency and nature of adverse events related to intravenous MEDI4736 (durvalumab) when given in combination with oral vistusertib.
      • Time Frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
      • Safety Issue:
      • Measure: Module F: The frequency and nature of adverse events related to the combination of intravenous MEDI4736 (durvalumab) and intravenous AZD9150.
      • Time Frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
      • Safety Issue:
      • Measure: Module G: The frequency and nature of adverse events related to intravenous MEDI4736 (durvalumab) when given in combination with oral selumetinib.
      • Time Frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
      • Safety Issue:
      • Measure: All Modules: Change from baseline in clinical chemistry parameters.
      • Time Frame: Days 1, 8, 15, and 22 of Cycle 1, Days 1, 15, and 22 of Cycles 2 and 3 and every 4 weeks thereafter, and at discontinuation.
      • Safety Issue:
      • Measure: All Modules: Change from baseline in haematology parameters.
      • Time Frame: Days 1, 8, 15, and 22 of Cycle 1, Days 1, 15, and 22 of Cycles 2 and 3 and every 4 weeks thereafter, and at discontinuation.
      • Safety Issue:
      • Measure: All Modules: Change from baseline in urinalysis results.
      • Time Frame: Days 1, 8, 15, and 22 of Cycle 1, Days 1, 15, and 22 of Cycles 2 and 3 and every 4 weeks thereafter, and at discontinuation.
      • Safety Issue:
      • Measure: All Modules: Change from baseline in vital signs.
      • Time Frame: Day 1 of Cycles 1, 2, 3, and 4 and every 4 weeks therafter, and at discontinuation.
      • Safety Issue:
      • Measure: All Modules: Change from baseline in physical examination findings.
      • Time Frame: Day 1 of Cycles 1, 2, 3, and 4 and every 4 weeks therafter, and at discontinuation.
      • Safety Issue:
      • Measure: All Modules: Change from baseline in ECG findings.
      • Time Frame: ECGs will be collected at screening, Day 1, Cycle 1and then Day 1 of each cycle from Cycle 2 onwards.
      • Safety Issue:
      • Measure: All Modules: Change from baseline in ejection fraction determined by assessing ECHO/MUGA scans.
      • Time Frame: Ejection fraction will be measured at screening, on Day 1, Cycle 1, and every 12 weeks thereafter (relative to the first dose of study drug) up to Cycle 7, and then every 16 weeks thereafter.
      • Safety Issue:
      • Measure: All Modules: Change from baseline in coagulation parameters
      • Time Frame: Coagulation parameters will be measured at screening, on Day 1, Cycle 1, and every 12 weeks thereafter (relative to the first dose of study drug) up to Cycle 7, and then every 16 weeks thereafter.
      • Safety Issue:
      • Measure: All Modules: Change from baseline in lipid profile
      • Time Frame: Lipid profile will be measured at screening, on Day 1, Cycle 1, and every 12 weeks thereafter (relative to the first dose of study drug) up to Cycle 7, and then every 16 weeks thereafter.
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Objective response rate (ORR)
      • Time Frame: 16 weeks and 52 weeks
      • Safety Issue:
      • Measure: Disease control rate (DCR)
      • Time Frame: 16 weeks and 52 weeks
      • Safety Issue:
      • Measure: Progression free survival (PFS)
      • Time Frame: up to 12 months
      • Safety Issue:
      • Measure: Duration of response (DoR)
      • Time Frame: up to 12 months
      • Safety Issue:
      • Measure: Overall survival (OS) rate at 1 year
      • Time Frame: 1 year
      • Safety Issue:
      • Measure: Plasma concentration of AZD4547 (Module A)
      • Time Frame: Blood samples will be taken pre-dose on Days 1 and 8 of Cycle 1; pre-dose and 2, 3, 4 and 6 hours post-dose on Day 1 of Cycle 2; and pre-dose and 2 to 4 hours post-dose on Day 1 of Cycle 3.
      • Safety Issue:
      • Measure: Plasma concentration of MEDI4736 (durvalumab) (Module A)
      • Time Frame: Blood samples will be taken pre-dose and end of infusion for Day 1 of Cycles 1 to 7 and for the post-Cycle 7 8-weekly assessments, and pre-dose for Day 8 of Cycle 1.
      • Safety Issue:
      • Measure: Plasma concentration of olaparib (Module B)
      • Time Frame: Blood samples will be taken on Day 3 of Cycles 1 and pre-dose and 4 hr post-dose. Serial samples on Day 3 of Cycle 3, pre-dose, 1, 2, 4, 6, 8, and 10 hr post-dose.
      • Safety Issue:
      • Measure: Plasma concentration of AZD1775 (Module C)
      • Time Frame: Blood samples will be taken on Day 8 at steady state at the following time points: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hr post-dose.
      • Safety Issue:
      • Measure: Plasma concentration of MEDI4736 (durvalumab) (Module C)
      • Time Frame: Blood samples will be taken on Days 1 and 8 of Cycle 1 pre-dose and at the end of infusion (1 hour). Samples will also be collected on Day 1 of Cycles 2 to 7 pre-dose and at the end of infusion.
      • Safety Issue:
      • Measure: Plasma concentration of MEDI4736 (durvalumab) (Module D)
      • Time Frame: Blood samples will be taken on Days 1 and 8 of Cycle 1
      • Safety Issue:
      • Measure: Plasma concentration of vistusertib (Module E)
      • Time Frame: Blood samples will be collected pre-dose, and 2 and 4 hr post-dose on Day 1 of Cycle 1; and pre-dose and 2 to 6 hr post-dose (matched to biopsy) on Day 2 of Cycle 2.
      • Safety Issue:
      • Measure: Plasma concentration of Medi4736 (durvalumab) (Module E).
      • Time Frame: Blood samples will be taken pre-dose and end of infusion for Day 1 of Cycles 1 to 7 and every 8 weeks thereafter and pre-dose for Day 8 of Cycle 1.
      • Safety Issue:
      • Measure: Plasma concentration of AZD9150 (Module F)
      • Time Frame: Blood samples will be taken pre-dose of Days -7, -5, and -3 of the lead-in portion and thereafter prior to dosing and at the ned of infusion on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (approximately 8 months).
      • Safety Issue:
      • Measure: Plasma concentration of MEDI4736 (durvalumab) (Module F).
      • Time Frame: Blood samples will be taken pre-dose and end of infusion for Day 1 of Cycles 1 to 7 and every 8 weeks thereafter and pre-dose for Day 8 of Cycle 1.
      • Safety Issue:
      • Measure: The presence of Anti-Drug Antibodies (ADA) and ADA neutralising antibodies to MEDI4736 will be assessed in patients receiving MEDI4736 in any sub-study module.
      • Time Frame: Blood samples will be collected prior to MEDI4736 dosing on Day 1 of Cycles 1, 2 and 4 and every 12 weeks thereafter (up to 12 months).
      • Safety Issue:

      Estimated Enrollment: 196

      Study Start Date: October 3, 2016

      Phase: Phase 1

      Eligibility:

      • Age: minimum 18 Years maximum 130 Years
      • Gender: All

      Inclusion Criteria:

      1. for all Modules:
      2. Metastatic MIBC
      3. 2nd/3rd line
      4. Failed adjuvant/neo-adjuvant chemotherapy <1 yr
      5. 1 lesion ≥10 mm at baseline in the longest diameter suitable for accurate repeated measurement
      6. WHO perf. status 0-1 For Module A:
      7. M/F ≥25
      8. Confirmation of FGFR3 mutation or FGFR fusion For Module B:
      9. Hgb ≥10 g/dL
      10. Deleterious mutation, deletion or truncation in any HRR genes For Module C:
      11. Tumour harbours a deletion or inactivating mutation of the CDKN2A or RB1 genes and/or amplification of CCNE1, MYC, MYCL or MYCN genes For Module E:
      12. Contraception must be sustained throughout treatment with vistusertib and 16 wks after last dose For Module F:
      13. Adequate organ and marrow function, defined as Leukocytes ≥3.0x10(exp9)/L; ANC ≥1.5x10(exp9)/L; platelets ≥100x10(exp9)/L
      14. Contraceptive measures must be sustained throughout treatment with AZD9150 and for 180 days after the last dose.

      Exclusion Criteria:

      1. for all Modules:
      2. Immunotherapy, chemotherapy, anticancer agents, radiotherapy <4 weeks, or radiotherapy for palliation <2 weeks, any study drugs <30 days.
      3. Major surgery <4 weeks
      4. Unresolved toxicities from prior therapy
      5. Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy
      6. Immunosuppressive drugs <28 days
      7. Any of the following: Autoimmune disease ≤2 yr; IBD; primary immunodeficiency; organ transplant requiring immunosuppressives
      8. Spinal cord compression or brain metastases, treated and stable & not requiring steroids for at least 4 weeks
      9. Severe or uncontrolled systemic disease
      10. Any of the following: Mean QTc ≥470 ms; abnormalities in resting ECG; factors that increase the risk of QTc prolongation or arrhythmia; uncontrolled hyper/hypotension; LVEF <55%; atrial fibrillation; NYHA Grade II-IV; severe valvular disease; uncontrolled angina; stroke/TIA <6 months; acute coronary syndrome <6 months
      11. Any of the following laboratory values: ANC <1.5x10(exp9)/L; Platelets <100x10(exp9)/L; Hgb <9.0 g/dL; ALT >2.5xULN or >5xULN with liver mets; Total bilirubin >1.5 times ULN or with Gilbert's disease ≥2×ULN; Creatinine >1.5xULN concurrent with creatinine clearance <50 mL/min; Corrected Ca >ULN, PO4 >ULN
      12. Active infection including tuberculosis, hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus. Patients with a past or resolved HBV infection are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
      13. Live attenuated vaccination <30 days For Module A:
      14. Prior exposure to: Nitrosourea or mitomycin C <6 weeks; any agent with FGFR inhibition as its primary pharmacology; AZD4547; potent inhibitors/inducers of CYP3A4, inhibitors of CYP2D6 or substrates of CYP3A4 <2 wks
      15. Ophthalmological criteria: RPED; laser treatment or intraocular injection for macular degeneration; age-related macular degeneration; retinal vein occlusion; retinal degenerative disease; other clinically relevant chorioretinal defect
      16. Refractory nausea/vomiting, chronic GI diseases, or previous bowel resection For Module B:
      17. Transfusion <120 days
      18. Concurrent medications that are strong inhibitors of cytochrome P450 (CYP) 3A (CYP3A) or strong inducers of CYP3A
      19. Previous treatment with PARP inhibitor, including olaparib
      20. Patients with history of MDS or AML For Module C:
      21. Prior exposure to any of the following: Nitrosourea or mitomycin C <6 wks; any agent with Wee1 inhibition as its primary pharmacology; prior treatment with AZD1775
      22. Any drugs or products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with narrow therapeutic index, or moderate to strong inhibitors/inducers of CYP3A4
      23. Herbal preparations
      24. Refractory nausea and vomiting or chronic GI diseases
      25. Cardiac disease <6 months For Module E:
      26. Minor surgery <14 days of first dose
      27. Exposure to specific substrates of OATP1B1, OATP1B3, MATE1 and MATE2K <5x half-life before treatment. Exposure to strong/moderate inhibitors/inducers of CYP3A4/5, Pgp (MDR1) and BRCP if taken within washout periods before the first dose
      28. Haemopoietic growth factors (filgrastim, sargramostim, GM-CSF) <14 days prior to treatment
      29. Other mTOR inhibitors
      30. Renal disease or renal tubular acidosis
      31. Uncontrolled Type 1 or 2 diabetes For Module F:
      32. AST ≤ 2.5xULN or ≤5xULN with liver metastases For Module G:
      33. Have had prior treatment with a MEK, Ras or Raf inhibitor.
      34. Any of the following ophthalmic criteria: Current or past history of central serous retinopathy, detachment of retinal pigmented epithelium, or retinal vein occlusion; intraocular pressure (IOP) >21 mmHg; uncontrolled glaucoma (irrespective of IOP)
      35. Baseline left ventricular ejection fraction (LVEF) <55% measured by echocardiogram (ECHO) or, if allowed, a multigated acquisition (MUGA) scan. Appropriate correction to be used if a MUGA is performed.
      36. Previous moderate or severe impairment of LVEF (<45% on echocardiography or equivalent on MUGA) even if full recovery has occurred.
      37. Male or female patients with reproductive potential and, as judged by the investigator, are not employing an effective method of birth control and female patients who are breastfeeding.
      38. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
      39. Receiving or have received systemic therapy with nitrosoureas, mitomycin or suramin within 6 weeks prior to starting study treatment.

      Contact:

      • AstraZeneca Clinical Study Information Center
      • 1-877-240-9479

      Locations:

      • Research Site
      • Los Angeles California 90033 United States
      • Research Site
      • Los Angeles California 90095 United States
      • Research Site
      • New Haven Connecticut 06510 United States
      • Research Site
      • Fort Myers Florida 33901 United States
      • Research Site
      • Baltimore Maryland 21231 United States
      • Research Site
      • Baltimore Maryland 21287-0013 United States
      • Research Site
      • Detroit Michigan 48202 United States
      • Research Site
      • Kansas City Missouri 64132 United States
      • Research Site
      • New York New York 10029 United States
      • Research Site
      • New York New York 10032 United States
      • Research Site
      • New York New York 10116 United States
      • Research Site
      • Cincinnati Ohio 45243 United States
      • Research Site
      • Cleveland Ohio 44195 United States
      • Research Site
      • Nashville Tennessee 37203 United States
      • Research Site
      • Milwaukee Wisconsin 53226 United States
      • Research Site
      • Edmonton Alberta T6G 1Z2 Canada
      • Research Site
      • Vancouver British Columbia V5Z 4E6 Canada
      • Research Site
      • Toronto Ontario M5G 2M9 Canada
      • Research Site
      • Montreal Quebec H3T 1E2 Canada
      • Research Site
      • Bordeaux 33075 France
      • Research Site
      • Caen 14000 France
      • Research Site
      • LYON cedex 08 69373 France
      • Research Site
      • Marseille Cedex 9 13273 France
      • Research Site
      • Saint Herblain Cedex 44805 France
      • Research Site
      • Toulouse Cedex 31100 France
      • Research Site
      • Badalona 08003 Spain
      • Research Site
      • Barcelona 08035 Spain
      • Research Site
      • Barcelona 08041 Spain
      • Research Site
      • Madrid 28040 Spain
      • Research Site
      • Cardiff CF14 2TL United Kingdom
      • Research Site
      • Edinburgh EH4 2XR United Kingdom
      • Research Site
      • Glasgow G12 0YN United Kingdom
      • Research Site
      • London EC1M 6BQ United Kingdom
      • Research Site
      • London W1G 6AD United Kingdom
      • Research Site
      • Manchester M20 4BX United Kingdom
      • Research Site
      • Plymouth PL6 8DH United Kingdom
      • Research Site
      • Southampton SO16 6YD United Kingdom

      View trial on ClinicalTrials.gov


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      Published June 29, 2017
    2. Application-based Perioperative Management of the Radical Cystectomy Patient

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      Application-based Perioperative Management of the Radical Cystectomy Patient


      Condition: Bladder Cancer

      Intervention:

      • Other: LifeScience Technologies application

      Purpose: The purpose of this study is to learn whether it is feasible to use the LifeScience Technologies application (LST app) in patients undergoing radical cystectomy with the eventual goal to reduce complications and readmissions to the hospital after surgery.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02942121

      Sponsor: University of Kansas Medical Center

      Primary Outcome Measures:

      • Measure: Compliance using LST app at home
      • Time Frame: 90 Days
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Patient-generated subjective global assessment (PG-SGA)
      • Time Frame: Baseline
      • Safety Issue:
      • Measure: Edmonton Frail Scale (EFS)
      • Time Frame: Baseline
      • Safety Issue:
      • Measure: Physician Office/Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) Survey Research (HealthStream™)
      • Time Frame: Change from Baseline to Day 90
      • Safety Issue:
      • Measure: Count of readmissions
      • Time Frame: Day 90
      • Safety Issue:

      Estimated Enrollment: 20

      Study Start Date: September 2016

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • Diagnosis of recurrent Non-muscle invasive bladder cancer (NMIBC) or Muscle-invasive Bladder Cancer (MIBC) and are candidates for radical cystectomy
      • Subjects must have an internet connection and be able and willing to use an applicable device. If patients do not have an applicable device, they must be willing to borrow an iPad from the study team (to be returned at the conclusion of the study).

      Exclusion Criteria:

      • No internet access

      Contact:

      • Eugene Lee, MD

      Location:

      • University of Kansas Medical Center
      • Kansas City Kansas 66160 United States

      View trial on ClinicalTrials.gov


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      Published June 29, 2017
    3. Clinical and patient reported outcomes of SPARE - a randomised feasibility study of selective bladder preservation versus radical cystectomy.

      To test the feasibility of a randomised trial in muscle invasive bladder cancer (MIBC) and compare outcomes in patients who receive neoadjuvant chemotherapy followed by radical cystectomy or selective bladder preservation, where definitive treatment (cystectomy or radiotherapy) is determined by response to chemotherapy.

      Published May 1, 2017
    4. Comparative Perioperative Outcomes in Septuagenarians and Octogenarians Undergoing Radical Cystectomy for Bladder Cancer-Do Outcomes Differ?

      Treatment choice for muscle invasive bladder cancer continues to be radical cystectomy. However, radical cystectomy carries a relatively high risk of morbidity and mortality compared with other urological procedures.

      Published September 11, 2017
    5. Current Concepts in the Management of Muscle Invasive Bladder Cancer.

      Bladder cancer is the ninth most common cancer in the world. Twenty to twenty-five percent of all newly diagnosed bladder cancers are muscle invasive in nature, and further, 20-25% of patients who are diagnosed with high-risk non-muscle invasive disease will eventually progress to muscle invasive disease in due course of time irrespective of adjuvant intravesical therapies.

      Published February 2, 2017
    6. Ethacrynic Acid Elimination in Non-Muscle Invasive Bladder Cancer Patients Undergoing Transurethral Resection

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      Ethacrynic Acid Elimination in Non-Muscle Invasive Bladder Cancer Patients Undergoing Transurethral Resection


      Condition: Bladder Cancer

      Intervention:

      • Drug: Ethacrynic Acid

      Purpose: Phase 1 study to provide quantitative characterization of the renal elimination of ethacrynic acid and metabolites in patients with non-muscle invasive bladder cancer (NMIBC) at the time of transurethral resection of bladder tumor

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02852564

      Sponsor: University of Kansas Medical Center

      Primary Outcome Measures:

      • Measure: Urine Concentration - Ethacrynic Acid and its conjugates
      • Time Frame: Baseline at 30 minutes before surgery
      • Safety Issue:
      • Measure: Urine Concentration - Ethacrynic Acid and its conjugates
      • Time Frame: During surgery
      • Safety Issue:
      • Measure: Urine Concentration - Ethacrynic Acid and its conjugates
      • Time Frame: 2 hours after surgery
      • Safety Issue:
      • Measure: Urine Concentration - Ethacrynic Acid and its conjugates
      • Time Frame: 4 hours after surgery
      • Safety Issue:
      • Measure: Excretion Rates - Ethacrynic Acid and its conjugates
      • Time Frame: 30 minutes before surgery
      • Safety Issue:
      • Measure: Excretion Rates - Ethacrynic Acid and its conjugates
      • Time Frame: during surgery
      • Safety Issue:
      • Measure: Excretion Rates - Ethacrynic Acid and its conjugates
      • Time Frame: 2 hours after surgery
      • Safety Issue:
      • Measure: Excretion Rates - Ethacrynic Acid and its conjugates
      • Time Frame: 4 hours after surgery
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Number of Participants with treatment-related adverse events as assessed by CTCAE 4.03
      • Time Frame: During and after surgery, up to 3 months following surgery
      • Safety Issue:
      • Measure: Number of Participants with Tumor Recurrence / Non-Recurrence using RECIST version 1.1
      • Time Frame: 90 days after surgery
      • Safety Issue:

      Estimated Enrollment: 12

      Study Start Date: August 2016

      Phase: Phase 1

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • NOTE: Both patients who will and will not receive standard of care concomitant mitomycin C are eligible to enroll in this study.
      • Ability to understand and the willingness to sign a written informed consent
      • Diagnosis of presumed non-muscle invasive bladder cancer based on office based cystoscopy (primary or recurrent), and planned transurethral resection of bladder tumor (TURBT)
      • Participants must have tumors with anticipated transurethral resection time ≤ 1 hour
      • Previous history of intravesical therapy allowed
      • Age ≥ 18 years
      • Performance Status 0-1
      • Adequate organ and marrow function as defined below:
      • leukocytes ≥ 3,000/mcL
      • absolute neutrophil count ≥ 1,500/mcL
      • platelets ≥ 100,000/mcl
      • total bilirubin within normal institutional limits
      • Aspartate Aminotransferase (AST) ≤ 2.5 X institutional upper limit of normal
      • Alanine Aminotransferase (ALT) ≤ 2.5 X institutional upper limit of normal
      • creatinine ≤ 2.5 X institutional upper limit of normal
      • Women of child-bearing potential (WOCP) and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately *A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
      • Has not undergone a hysterectomy or bilateral oophorectomy; or
      • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) EXCLUSION CRITERIA: Participants meeting any of the

      Exclusion Criteria:

      • Participants meeting any of the exclusion criteria at baseline will be excluded from study participation.
      • Current or anticipated use of other investigational agents.
      • Patient has known nodal or distant metastatic disease. Patients with nodal or metastatic disease require systemic chemotherapy. Furthermore, they should be excluded from this clinical trial because of their poor overall prognosis.
      • Patients with locally advanced bladder cancer based on cross-sectional imaging (suspicion of extravesical disease or hydronephrosis)
      • Patients with tumors with anticipated transurethral resection time greater than 1 hour
      • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ethacrynic acid or other agents used in study.
      • Systolic blood pressure < 90 mmHg and/or diastolic blood pressure < 50 mmHg
      • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
      • Pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants.

      Location:

      • The University of Kansas Medical Center
      • Kansas City Kansas 66160 United States

      View trial on ClinicalTrials.gov


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      Published June 29, 2017
    7. Identification and Treatments of Basal Like Bladder Cancer (Study on Human Tumor Samples and Animal Models)

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      Identification and Treatments of Basal Like Bladder Cancer (Study on Human Tumor Samples and Animal Models)


      Condition: Muscle Invasive Bladder Cancer, Molecular Taxonomy

      Intervention:

      • Other: biomarker study

      Purpose: Muscle invasive (MIBC) and/or metastatic bladder cancer is associated with poor prognosis and no target therapies for this pathology are currently validated. By 40 gene expression signature realized on frozen samples, we have previously identified an aggressive sub-class of MIBC, called basal. This sub-class (20% of MIBC) showed strong EGFR dependence in vitro and in vivo (Rebouissou et al. Science Translational Medicine 2014). This observation suggests a possible response to EGFR targeted therapy in patients of this subgroup. Our aim is to establish a standard diagnostic tool to differentiate the basal subtype of bladder cancer and evaluate the effect of anti-EGFR therapy, by analyzing previous clinical trial (GETUG19) and preclinical models, which compare the classical chemotherapy to anti-EGFR associated chemotherapy.

      Study Type: Observational

      Clinical Trials Identifier NCT 8-digits: NCT02648100

      Sponsor: Assistance Publique - Hôpitaux de Paris

      Primary Outcome Measures:

      • Measure: Progression free survival
      • Time Frame: 5 years
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Overall survival
      • Time Frame: 5 years
      • Safety Issue:
      • Measure: Specific survival
      • Time Frame: 5 years
      • Safety Issue:

      Estimated Enrollment: 911

      Study Start Date: March 2014

      Eligibility:

      • Age: minimum 18 Years maximum 70 Years
      • Gender: All

      Inclusion Criteria:

      1. Muscle invasive bladder cancer Treatment by cystectomy Adjuvant chemotherapy for 3rd cohort Clinical trial GETUG 19 for 4th cohort

      Exclusion Criteria:

      1. FFPE material not available Follow-up data not available

      Contact:

      • Yves ALLORY, MD, PhD
      • (0)1 49 81 27 29 Ext. +33

      Location:

      • Henri Mondor Hospital
      • Creteil 94010 France

      View trial on ClinicalTrials.gov


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      Published June 29, 2017
    8. Impact of Positron Emission Tomography (PET) Imaging in Muscle-invasive Urothelial Carcinoma of the Bladder Staging

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      Impact of Positron Emission Tomography (PET) Imaging in Muscle-invasive Urothelial Carcinoma of the Bladder Staging


      Condition: Muscle-invasive Bladder Cancer

      Intervention:

      • Other: Whole-body FDG PET-CT

      Purpose: Bladder cancer is the fifth most common cancer in Canada and there has been relatively little progress in altering its clinical course over the last three decades. One of the major problems identified in the management of this disease, is under staging of muscle invasive disease which can lead to suboptimal treatment and outcomes. PET-CT has the potential to more accurately stage MIBC than standard CT by detecting pelvic adenopathy and/or distant sites of disease that may not be found on standard imaging. In the former situation, more aggressive therapy with extended lymph node dissection and/or neoadjuvant chemotherapy prior to cystectomy can be offered. While in the latter situation patients can be spared the morbidity of a cystectomy performed in a setting of metastatic disease. This study will address whether PET-CT adds a clinically meaningful difference in care.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02462239

      Sponsor: Ontario Clinical Oncology Group (OCOG)

      Primary Outcome Measures:

      • Measure: Treatment received
      • Time Frame: 5 years
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Disease-free survival
      • Time Frame: 5 years
      • Safety Issue:
      • Measure: Overall survival
      • Time Frame: 5 years
      • Safety Issue:
      • Measure: Quality of life analysis
      • Time Frame: 5 years
      • Safety Issue:
      • Measure: Health economic analysis
      • Time Frame: 5 years
      • Safety Issue:

      Estimated Enrollment: 291

      Study Start Date: January 2016

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • Men and women with newly diagnosed muscle-invasive high grade urothelial carcinoma of the bladder (TNM stage T2a-T4a, N0-3, M0), who are eligible for either radical cystectomy or radiotherapy-based bladder conservation.
      • Being considered for treatment of curative intent.

      Exclusion Criteria:

      • Age < 18 years.
      • ECOG performance status >2.
      • Predominant histology (>50% of specimen) involves non-urothelial cell carcinoma.
      • Prior partial cystectomy.
      • Prior pelvis surgery that obviates a completed extended lymphadenectomy (e.g., aorto-femoral/iliac bypass) or for whom the surgeon feels that their ability to perform a standard or extended pelvic node dissection would be compromised.
      • Contraindications to FDG PET-CT.
      • Inability to lie supine for imaging with PET-CT.
      • Inadequate hepatic function: (i) Bilirubin >1.5 X ULN and (ii) SGOT and Alkaline phosphatase >3 X ULN
      • History of another invasive malignancy within the previous 5 years with the exception of non-melanoma skin cancer.
      • Known pregnancy or lactating female.
      • Inability to complete the study or required follow-up.

      Contact:

      • Marc L Filion, MSc, CCRP
      • 905-527-2299 Ext. 42611

      Locations:

      • Juravinski Cancer Centre
      • Hamilton Ontario L8V 5C2 Canada
      • London Regional Cancer Centre
      • London Ontario N6A 4L6 Canada
      • Ottawa Hospital Regional Cancer Centre
      • Ottawa Ontario K1H 8L6 Canada
      • Thunder Bay Regional Health Sciences Centre
      • Thunder Bay Ontario P7B 6V4 Canada
      • Sunnybrook Odette Cancer Centre
      • Toronto Ontario M4N 3M5 Canada
      • Princess Margaret Cancer Centre
      • Toronto Ontario M5G 2M9 Canada

      View trial on ClinicalTrials.gov


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      Published June 29, 2017
    9. Improving Clinical Staging for Muscle Invasive Bladder Cancer Through Molecular Profiling and Improved Imaging

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      Improving Clinical Staging for Muscle Invasive Bladder Cancer Through Molecular Profiling and Improved Imaging


      Condition: Bladder Cancer

      Intervention:

      • Procedure: Tissue Biopsy
      • Procedure: Magnetic Resonance Imaging (MRI)

      Purpose: The goal of this research study is to improve detection of cancer outside of the bladder through genetic testing and improved imaging.

      Study Type: Observational

      Clinical Trials Identifier NCT 8-digits: NCT02203136

      Sponsor: M.D. Anderson Cancer Center

      Primary Outcome Measures:

      • Measure: Detection Improvement of Cancer Outside of the Bladder
      • Time Frame: 4 weeks
      • Safety Issue:

      Estimated Enrollment: 100

      Study Start Date: June 2014

      Eligibility:

      • Age: minimum N/A maximum N/A
      • Gender: All

      Inclusion Criteria:

      1. Patients with biopsy proven bladder cancer of any age will be eligible for enrollment.

      Exclusion Criteria:

      1. Contraindication to pelvic MRI (metallic implants/hardware, claustrophobia)
      2. Participants who have previously received chemotherapy as part of multimodal therapy.

      Contact:

      • Neema Navai, MD
      • 713-792-3250

      Location:

      • University of Texas MD Anderson Cancer Center
      • Houston Texas 77030 United States

      View trial on ClinicalTrials.gov


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      Published June 29, 2017
    10. LCCC 1209: Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography-Magnetic Resonance Imaging (FDG-PET-MRI) for Staging of Muscle-Invasive Bladder Cancer

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      LCCC 1209: Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography-Magnetic Resonance Imaging (FDG-PET-MRI) for Staging of Muscle-Invasive Bladder Cancer


      Condition: Bladder Cancer

      Intervention:

      • Procedure: FDG PET/MR

      Purpose: This prospective pilot study will enroll 30 patients with cT2/T3-N0-M0 urothelial carcinoma of the bladder for whom radical cystectomy with pelvic lymph node dissection is planned. This pilot study is designed to provide preliminary information on the accuracy of [18F] Fluorodeoxyglucose Positron Emission Tomography MRI (FDG-PET-MRI) in the staging of muscle-invasive bladder cancer.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT01655745

      Sponsor: UNC Lineberger Comprehensive Cancer Center

      Primary Outcome Measures:

      • Measure: Sensitivity and specificity of the FDG-PET-MRI for staging of muscle-invasive bladder cancer
      • Time Frame: 3 years
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Association of FDG-PET-MRI with RFS, DSS and OS in patients with muscle-invasive bladder cancer
      • Time Frame: 3 years
      • Safety Issue:

      Estimated Enrollment: 30

      Study Start Date: August 2012

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • ≥ 18 years of age (no upper age limit)
      • Informed consent obtained and signed
      • cT2/T3-N0-M0 urothelial carcinoma of the bladder
      • Planned radical cystectomy with pelvic lymph node dissection
      • No known local regional or distant metastatic disease
      • Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to FDG-PET-MRI

      Exclusion Criteria:

      • History of severe reaction to contrast-enhanced CT scan
      • Poorly controlled diabetes mellitus
      • Inability to tolerate PET and/or MRI
      • Presence of pacemaker or intracranial aneurysm clip
      • Serum creatinine >1.8 mg/dL OR GFR < 30mL/min
      • Pregnant or lactating female
      • Inability to lie flat for >1 hour
      • Body Mass Index (BMI) >35
      • History of a prior malignancy within past 5 years are excluded unless they have been disease free for 3 or more years or unless they have a completely resected non-melanoma skin cancer.
      • Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study

      Contact:

      • Kristine Baluyot
      • 919-843-5420

      Location:

      • Lineberger Comprehensive Cancer Center
      • Chapel Hill North Carolina 27599 United States

      View trial on ClinicalTrials.gov


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      Published January 25, 2017
    11. Lymphadenectomy in Urothelial Carcinoma in the Renal Pelvis and Ureter

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      Lymphadenectomy in Urothelial Carcinoma in the Renal Pelvis and Ureter


      Condition: Ureteral Neoplasms

      Intervention:

      • Procedure: Lymphadenectomy in conjugation with nephroureterectomy
      • Procedure: Nephroureterectomy without lymphadenectomy

      Purpose: Two out of three tumours in the upper urinary tract are located in the renal pelvis. Muscle-invasive urothelial carcinoma is probably more common among tumours in the upper urinary tract compared to tumours in the urinary bladder. Thus, muscle-invasive tumours represent approximately 45 % of renal pelvic tumours compared to 25 % of tumours within the urinary bladder. As in the bladder, lymph node metastases are rare in non-muscle invasive disease. Information regarding indications, extent and possible curative potential is currently lacking for lymphadenectomy in conjunction with nephroureterectomy for urothelial carcinoma in the upper urinary tract (UUTUC). There are, however, retrospective series with survival data for patients with lymph node metastasis that report long term survival after surgery as monotherapy [4] with similar survival proportions as in bladder cancer with lymph node metastases after radical cystectomy. A retrospective study from Tokyo was expanded to the only available prospective study, where 68 patients with UUTUC were submitted to template-based lymphadenectomy. Another retrospective study by the same Japanese group, showed that 5-year cancer-specific and recurrence-free survival was significantly higher in the complete lymphadenectomy group than in the incomplete lymphadenectomy or without lymphadenectomy groups. Tanaka N et al. reported recurrence rate after nephroureterectomy without lymphadenectomy at 1 and 3 years were 18.9 and 29.8 %, respectively.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02607709

      Sponsor: Zealand University Hospital

      Primary Outcome Measures:

      • Measure: Recurrence free survival
      • Time Frame: Five years
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Incidence of metastasis
      • Time Frame: Five years
      • Safety Issue:

      Estimated Enrollment: 366

      Study Start Date: June 2016

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      1. Age above 18 years
      2. Locally advanced high grade urothelial carcinoma in the renal pelvis or upper 2/3 of the ureter (Clinical stage > T1)
      3. Patient with ECOG performance score of 2 and less.
      4. Able to give informed consent

      Exclusion Criteria:

      1. Clinical suspicion of non-muscle invasive UUTUC
      2. Metastatic urothelial carcinoma for the renal pelvis or upper 2/3 of the ureter
      3. Inability to understand written consent forms or give consent

      Contact:

      • Nessn H Azawi, MB.Ch.B.
      • 004526393034

      Location:

      • Roskilde Hospital
      • Roskilde 4000 Denmark

      View trial on ClinicalTrials.gov


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      Published June 29, 2017
    12. MDSC Clinical Assay for Cancer Detection and Monitoring in Bladder Carcinoma

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      MDSC Clinical Assay for Cancer Detection and Monitoring in Bladder Carcinoma


      Condition: No Evidence of Disease, Stage II Bladder Cancer, Stage III Bladder Cancer, Stage IVA Bladder Cancer, Stage IVB Bladder Cancer

      Intervention:

      • Other: Cytology Specimen Collection Procedure
      • Other: Laboratory Biomarker Analysis

      Purpose: This pilot research trial studies how well myeloid derived suppressor cells (MDSC) clinical assay works in finding and monitoring cancer cells in blood and urine samples from patients with or without localized or metastatic bladder cancer. Studying samples of blood and urine from patients with or without bladder cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer and may help doctors improve ways to diagnose and treat patients.

      Study Type: Observational

      Clinical Trials Identifier NCT 8-digits: NCT02735512

      Sponsor: University of Southern California

      Primary Outcome Measures:

      • Measure: Change in MDSC level in patients with known localized, muscle-invasive bladder cancer who undergo surgical treatment
      • Time Frame: Baseline to up to 4 months
      • Safety Issue:
      • Measure: Change in MDSC level in patients with known metastatic bladder cancer who undergo systemic treatment
      • Time Frame: Baseline to up to 6 months
      • Safety Issue:
      • Measure: Change in MDSC level in patients with no history of cancer
      • Time Frame: Baseline to 4 months
      • Safety Issue:
      • Measure: Change in tumor burden evaluated by radiographic imaging
      • Time Frame: Baseline to up to 1 year
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Change in urine cytology analysis
      • Time Frame: Baseline to up to 4 months
      • Safety Issue:

      Estimated Enrollment: 63

      Study Start Date: March 1, 2016

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      Eligibility:

      • Age: minimum N/A maximum N/A
      • Gender: All

      Inclusion Criteria:

      • Subjects must meet the criteria for one of the three following groups:
      • Normal patients- aged 40 years and older with no evidence of hematuria or cancer
      • Patients with localized bladder cancer diagnosed by cystoscopy and pathology: T2N0M0 or T3N0M0 who have not received neoadjuvant chemotherapy
      • Patients with metastatic bladder cancer: newly diagnosed with no previous treatment for metastatic disease
      • Ability to understand and the willingness to sign a written informed consent

      Exclusion Criteria:

      • For normal subject arm: evidence of cancer or hematuria
      • For localized bladder cancer: evidence of metastatic disease, second cancer, prior chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
      • For metastatic bladder cancer: prior therapy for metastatic disease
      • Uncontrolled intercurrent illness including, but not limited to previous or current history of second malignancy unrelated to bladder cancer; autoimmune disease or immune deficiency, chronic treatment with immunomodulatory therapies (e.g. glucocorticoids); significant trauma, surgery, or infection in the past two weeks or psychiatric illness/social situations that would limit compliance with study requirements

      Contact:

      • Cheryl Kefauver, RN
      • 323-865-3000

      Location:

      • USC / Norris Comprehensive Cancer Center
      • Los Angeles California 90033 United States

      View trial on ClinicalTrials.gov


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      Published June 29, 2017
    13. Muscle Invasive Bladder Cancer: External Beam Radiotherapy as an Alternative for Cystectomy

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      Muscle Invasive Bladder Cancer: External Beam Radiotherapy as an Alternative for Cystectomy


      Condition: Toxicity

      Intervention:

      • Radiation: external beam radiotherapy (EBRT)

      Purpose: In this phase 1 trial, the investigators will prospectively evaluate 3 different external beam radiotherapy (EBRT) schedules. In every schedule, the whole bladder will be treated to 40 Gray (Gy) in 20 fractions, 5 fractions/week, 4 weeks in total. Based on the summation of abnormalities seen on pre- (initial tumor region) and post transurethral resection zone of fibrosis Diffusion weighted-magnetic resonance imaging (MRI) images the tumor region is delineated and defined as a gross tumor volume (GTV). The GTV will be treated using a simultaneous integrated boost (SIB): without extending the 4-weeks treatment period, 3 different dose levels will be implemented in order to increase the biological equivalent dose (BED), as muscle invasive bladder cancer has been shown to be dose-sensitive.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02748200

      Sponsor: University Hospital, Ghent

      Primary Outcome Measures:

      • Measure: Number of participants with treatment-related adverse events as assessed by Radiation Therapy Oncology Group toxicity scale
      • Time Frame: 3 months after radiotherapy
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Number of participants free from local relapse assessed on cystoscopy and Magnetic Resonance Imaging
      • Time Frame: 12 months after radiotherapy
      • Safety Issue:

      Estimated Enrollment: 9

      Study Start Date: March 2015

      Phase: Phase 1

      Eligibility:

      • Age: minimum 18 Years maximum 80 Years
      • Gender: All

      Inclusion Criteria:

      • histological proven diagnosis of muscle invasive bladder cancer
      • stage
      • World Health Organisation performance state 0-2
      • signed informed consent

      Exclusion Criteria:

      • contra-indication for Diffusion-Weighted-Magnetic resonance imaging

      Contact:

      • Valérie Fonteyne, MD, PhD

      Location:

      • Ghent University Hospital
      • Ghent 9000 Belgium

      View trial on ClinicalTrials.gov


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      Published June 29, 2017
    14. Neoadjuvant Gemcitabine, Cisplatin, Plus Nivolumab in Patients With Muscle-invasive Bladder Cancer With Selective Bladder Sparing

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      Neoadjuvant Gemcitabine, Cisplatin, Plus Nivolumab in Patients With Muscle-invasive Bladder Cancer With Selective Bladder Sparing


      Condition: Bladder Cancer

      Intervention:

      • Drug: Nivolumab
      • Drug: Gemcitabine
      • Drug: Cisplatin

      Purpose: This is a phase 2 trial seeking to define the safety and activity of gemcitabine, cisplatin, plus nivolumab as neoadjuvant therapy in patients with muscle-invasive bladder cancer and to define the role of clinical complete response in predicting benefit in patients opting to avoid cystectomy.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT03558087

      Sponsor: Matthew Galsky

      Primary Outcome Measures:

      • Measure: Determine the clinical complete response rate (cT0 or cTa) with gemcitabine, cisplatin, plus nivolumab
      • Time Frame: 24 months
      • Safety Issue:
      • Measure: Determine the ability of clinical complete response (cT0 or cTa) to predict benefit from treatment.
      • Time Frame: 24 months
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Assess Adverse Events
      • Time Frame: 24 months
      • Safety Issue:
      • Measure: Bladder intact overall survival
      • Time Frame: 24 Months
      • Safety Issue:
      • Measure: Recurrence-free survival
      • Time Frame: 24 months
      • Safety Issue:
      • Measure: Pathologic complete response rate in patients undergoing cystectomy
      • Time Frame: 24 Months
      • Safety Issue:
      • Measure: Determine the association between a prespecified panel of genomic biomarkers and benefit from treatment in patients achieving a clinical complete response.
      • Time Frame: 24 months
      • Safety Issue:

      Estimated Enrollment: 63

      Study Start Date: July 13, 2018

      Phase: Phase 2

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • ECOG Performance Status of ≤ 1 within 28 days prior to registration.
      • Histological evidence of clinically localized muscle-invasive urothelial cancer of the bladder (i.e., ct2-4n0m0). candidate for cystectomy as per treating physician.
      • Demonstrate adequate organ function per listed criteria:
      • Absolute Neutrophil Count (ANC): ≥ 1.5 x 10^9/L
      • Hemoglobin (Hgb): ≥ 9 g/dL
      • Platelets: ≥ 100 x 10^9/L
      • Calculated creatinine clearance: Creatinine ≤ 1.5 or creatinine clearance ≥ 60 mL/min
      • Bilirubin: ≤ 1.5 × upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
      • Aspartate aminotransferase (AST) : ≤ 3 × ULN
      • Alanine aminotransferase (ALT) : ≤ 3 × ULN
      • All subjects must have adequate archival tissue submitted prior to registration (i.e., at least 15 unstained slides or paraffin block).
      • Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception.
      • Women of childbearing potential must have a negative serum or urine pregnancy within 7 days prior to C1D1.
      • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year.

      Exclusion Criteria:

      • Prior treatment with systemic chemotherapy for muscle-invasive urothelial cancer of the bladder
      • Active infection requiring systemic therapy
      • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
      • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
      • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
      • Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
      • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
      • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
      • Grade ≥ 2 neuropathy (NCI CTCAE version 4).
      • Prior radiation therapy for bladder cancer
      • Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (RNA) or hepatitis C antibody (HCV antibody) indicating acute or chronic infection.
      • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
      • Evidence of interstitial lung disease or active, non-infectious pneumonitis.
      • Solid organ or allogeneic stem cell transplant

      Contact:

      • Matthew Galsky, MD
      • 212-659-5599

      Locations:

      • City of Hope
      • Duarte California 91010 United States
      • Univerity of Southern California
      • Los Angeles California 90033 United States
      • Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center
      • New York New York 10029 United States
      • Oregon Health & Science University
      • Portland Oregon 97239 United States
      • Penn Medicine Abramson Cancer Center
      • Philadelphia Pennsylvania 19104 United States
      • Huntsman Cancer Institute University of Utah
      • Salt Lake City Utah 84112 United States
      • University of Wisconsin
      • Madison Wisconsin 53705 United States

      View trial on ClinicalTrials.gov


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      Published November 20, 2018
    15. Open-Label, Multicenter, Ph 3 Study to Evaluate the Efficacy and Tolerability of Intravesical Vicinium™ in Subjects With Non Muscle-Invasive Carcinoma in Situ and/or High-Grade Papillary Disease of the Bladder Treated With BCG

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      Open-Label, Multicenter, Ph 3 Study to Evaluate the Efficacy and Tolerability of Intravesical Vicinium™ in Subjects With Non Muscle-Invasive Carcinoma in Situ and/or High-Grade Papillary Disease of the Bladder Treated With BCG


      Condition: Bladder Cancer

      Intervention:

      • Biological: Vicinium

      Purpose: Because of the high risk for development of muscle invasive disease, cystectomy is recommended for CIS, high-grade Ta and T1 patients who experience disease recurrence following intravesical therapy. Vicinium is an experimental agent that may provide an alternative to cystectomy

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02449239

      Sponsor: Viventia Bio

      Primary Outcome Measures:

      • Measure: Complete response rate
      • Time Frame: Up to 24 months
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Recurrence Rate
      • Time Frame: Patients will be followed for up to 104 weeks
      • Safety Issue:
      • Measure: Event-free survival
      • Time Frame: Time to event endpoint; patients will be followed for up to 104 weeks
      • Safety Issue:
      • Measure: Number of patients with adverse events as a measure of tolerability
      • Time Frame: Every 4 weeks up to 104 weeks
      • Safety Issue:
      • Measure: Changes in ECG
      • Time Frame: Every 4 weeks up to 104 weeks
      • Safety Issue:
      • Measure: Changes in vital signs
      • Time Frame: Every 4 weeks up to 104 weeks
      • Safety Issue:
      • Measure: Changes in laboratory or physical examination
      • Time Frame: Every 4 weeks up to 104 weeks
      • Safety Issue:
      • Measure: Complete response rate
      • Time Frame: Months 3, 6, 9, 12, 15,18, 21 and 24
      • Safety Issue:
      • Measure: Time to cystectomy
      • Time Frame: Time to event endpoint; patients will be followed for up to 104 weeks
      • Safety Issue:
      • Measure: Time to disease recurrence
      • Time Frame: Time to event endpoint; patients will be followed for up to 104 weeks
      • Safety Issue:
      • Measure: Time to progression
      • Time Frame: Time to event endpoint; patients will be followed for up to 104 weeks
      • Safety Issue:
      • Measure: Progression-free survival
      • Time Frame: Time to event endpoint; patients will be followed for up to 104 weeks
      • Safety Issue:
      • Measure: Overall survival
      • Time Frame: Time to event endpoint; patients will be followed for up to 104 weeks
      • Safety Issue:

      Estimated Enrollment: 134

      Study Start Date: August 2015

      Phase: Phase 3

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • 1. Histologically-confirmed non muscle-invasive urothelial carcinoma (transitional cell carcinoma) of the bladder as follows: 1. CIS (with or without papillary disease) OR 2. Any grade T1 papillary disease OR 3. High-grade Ta papillary disease based on a biopsy within 8 weeks of the initial dose of study treatment. If multiple bladder biopsies are required to confirm eligibility, the last bladder biopsy to the initial dose of study treatment must be within 8 weeks. This diagnosis must be confirmed by the independent central pathology reviewer prior to subject enrollment. A subject with persistent T1 disease on the second (i.e., restaging) TURBT may be enrolled in this study only if the investigator documents the subject declines cystectomy. 2. Subjects must have received adequate BCG treatment defined as at least 2 courses of BCG, i.e., at least one induction and one maintenance course or at least 2 induction courses. The initial induction course must be at least 5 treatments within a 7-week period. The second course (induction or maintenance) must be at least 2 treatments within a 6-week period. The "5+2" doses of BCG must be given within approximately 1 year (i.e., the start of one course to start of the second course within 12 months ±1 month) and for the same disease episode for which the subject is enrolling. Treatment must be considered "full-dose" BCG (see Section 10). If additional doses or courses of BCG above the minimum "5+2" are given, these do not have to be within the same approximate 12 month timeframe. Subjects who were unable to receive at least 5 doses of BCG in a first course and at least 2 doses of BCG in a second course due to intolerance are not eligible. Subjects who began their initial course of BCG with "full-dose" BCG and required dose-reductions due to adverse events but are still able to tolerate at least "5+2" doses of BCG are considered to meet the requirement for "adequate BCG." Subjects who received less than "full dose" BCG (e.g., 1/3rd dosing) as a standard regimen and not due to dose reductions because of AEs are not eligible. The BCG may have been given in combination with interferon. When BCG is given simultaneously in combination with interferon, 1/3rd dosing of BCG is acceptable. 3. The subject's disease is refractory or has relapsed following adequate BCG treatment. Refractory disease is defined as disease which persists at the first evaluation following adequate BCG. Relapsed disease is defined as having a complete response to adequate BCG but recurs at a subsequent evaluation. Subjects will enroll into one of three cohorts based on their type of disease and the time to refractory/relapsed disease following their last dose of BCG as follows:
      • Cohort 1: Subjects with CIS with or without associated papillary disease whose disease is determined to be refractory or relapsed within 6 months of the last dose of adequate BCG treatment.
      • Cohort 2: Subjects with CIS with or without associated papillary disease whose disease is determined to be refractory or relapsed more than 6 months but within 11 months of the last dose of adequate BCG treatment.
      • Cohort 3: Subjects with high-grade Ta or any grade T1 papillary disease (without CIS) whose disease is determined to be refractory or relapsed within 6 months of the last dose of adequate BCG treatment. For eligibility and cohort assignment, 6 months is defined as 30 weeks i.e., 26 weeks (6 months) plus an additional 4 weeks to accommodate scheduling variations and for diagnostic work-up and 11 months is defined as 50 weeks i.e., 48 weeks (11 months) plus an additional 2 weeks to accommodate scheduling variations and for diagnostic work-up. For subjects enrolling in Cohort 2: The investigator documents he/she would not treat the subject with additional BCG at the time of study entry. 4. Male or non-pregnant, non-breastfeeding female, age 18 years or older at date of consent. 5. All women of childbearing potential (WOCBP) must have a negative pregnancy test within 7 days of the first dose of study therapy. A woman is not of childbearing potential if she has undergone surgical sterilization (bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy) or if she is ≥55 years of age and has had no menstrual bleeding of any kind including menstrual period, irregular bleeding, spotting, etc., for at least 12 months and there is no other cause of amenorrhea (e.g., hormonal therapy, prior chemotherapy). 6. All sexually active subjects agree to use barrier contraception (i.e., condoms) while receiving study treatment and for 120 days following their last dose of study treatment. WOCBP and males whose sexual partners are WOCBP agree to use barrier contraception and a second form of contraception while receiving study treatment and for 120 days following their last dose of study treatment. 7. Karnofsky performance status ≥ 60 (Appendix 1). 8. Adequate organ function, as defined by the following criteria:
      • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x upper limit of normal (ULN);
      • Total serum bilirubin ≤ 1.5 x ULN (CTCAE Grade ≤ 1);
      • Serum creatinine ≤ 1.5 x ULN; or a creatinine clearance ≥40 mL/min;
      • Hemoglobin ≥8.0 g/dL;
      • Absolute neutrophil count ≥1500/mm3;
      • Platelets ≥75,000/mm3 9. Ability to understand and sign an Independent Ethics Committee- or Institutional Review Board-approved informed consent document indicating that the subject (or legally acceptable representative) has been informed of all aspects of the trial and is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. The informed consent document must be signed prior to the subject undergoing tests or procedures solely for determining study eligibility and prior to receiving any protocol treatment.

      Exclusion Criteria:

      • 1. The subject is pregnant or breastfeeding. 2. Evidence of urethral or upper tract transitional cell carcinoma (TCC) within the past 2 years. Subjects with T1 disease must have no evidence of upper or lower tract disease or a more advanced stage of disease by CT urogram or MRI urogram of the abdomen and pelvis performed within 8 weeks of the first dose of study treatment. If intravenous contrast is contraindicated, retrograde ureteropyelography, or CT or MRI without intravenous contrast may be performed. 3. Subjects with hydronephrosis, except for those subjects where hydronephrosis has been longstanding (i.e., predates the diagnosis of the CIS, Ta or T1 by more than 2 years) and diagnostic evaluation at Screening shows no evidence of tumor. Subjects with hydronephrosis that is unequivocally unrelated to upper tract malignancy may be considered eligible with Sponsor approval. 4. Any intravesicular or other chemotherapy treatment within 2 weeks or any investigational agent within 4 weeks prior to the initial dose of study drug. 5. History of recurrent severe urinary tract infections (UTIs) per investigator judgment. Subjects with a current UTI requiring antibiotic treatment may defer the initiation of Vicinium treatment on Day 1 until resolution of the UTI (even if this extends the screening period requirements to start of Vicinium treatment). 6. Active, uncontrolled impairment of the urogenital, renal, hepatobiliary, cardiovascular, gastrointestinal, neurologic or hematopoietic systems which, in the opinion of the Investigator, would predispose the subject to the development of complications from the administration of intravesical therapy and/or general anesthesia. 7. The subject has a diagnosis of another malignancy within 2 years before the first dose of study treatment, except for superficial skin cancer or localized solid tumors deemed cured by surgery and not treated with systemic anticancer therapy and not expected to require anticancer therapy in the next 2 years i.e., while the subject may be taking study treatment. However, subjects with low-risk prostate cancer, e.g.:
      • Clinically localized disease (≤T2a) and
      • Gleason score 6 (3+3) and
      • Serum PSA <10 ng/mL undergoing active surveillance may be enrolled with agreement of the sponsor. 8. A QTc interval of >470 msec by the Fridericia formula (QTcF), at the Screening ECG. If the subject's QTcF is >470 msec on the initial ECG, a total of 3 ECGs should be obtained at least 3 minutes apart and all within 30 minutes. The average of the 3 QTcF's will be used to determine eligibility. Known or suspected causes of prolonged QTc can be treated (e.g., hypocalcemia, hypokalemia, hypomagnesimia) and the ECGs may be repeated. If the subject initiates treatment with a drug known to prolong the QTc during the Screening period after the initial Screening ECGs were obtained, the Screening ECGs must be repeated once the new drug has reached steady state to ensure the average QTcF remains ≤470 msec. For subject's whose heart rate is <60 bpm, the Bazett correction formula (QTcB) may be used. 9. Subjects who, in the opinion of the Investigator, cannot tolerate intravesical administration or intravesical surgical manipulation (cystoscopy, biopsy) due to the presence of serious comorbid condition(s) (e.g., uncontrolled cardiac or respiratory disorders). 10. Local or severe allergy to any components of the drug regimen.

      Contact:

      • Erminia Cafasso
      • 973-366-1901

      Locations:

      • Birmingham Alabama 35294 United States
      • Phoenix Arizona 85032 United States
      • Tucson Arizona 85741 United States
      • Little Rock Arkansas 72211 United States
      • Los Angeles California 90017 United States
      • Los Angeles California 90048 United States
      • Los Angeles California 90089 United States
      • Los Angeles California 90095 United States
      • Redwood City California 94062 United States
      • San Bernardino California 92404 United States
      • Sherman Oaks California 91411 United States
      • Torrance California 90505 United States
      • Englewood Colorado 80113 United States
      • Washington District of Columbia 20010 United States
      • Bradenton Florida 34205 United States
      • Daytona Beach Florida 32114 United States
      • Orlando Florida 32803 United States
      • Saint Petersburg Florida 33710 United States
      • Tampa Florida 33612 United States
      • Wellington Florida 33449 United States
      • Atlanta Georgia 30322 United States
      • Honolulu Hawaii 96813 United States
      • Coeur d'Alene Idaho 83814 United States
      • Meridian Idaho 83642 United States
      • Chicago Illinois 60612 United States
      • Lake Barrington Illinois 60010 United States
      • Melrose Park Illinois 60160 United States
      • Jeffersonville Indiana 47130 United States
      • Fairway Kansas 66205 United States
      • Lenexa Kansas 66214 United States
      • Wichita Kansas 67208 United States
      • New Orleans Louisiana 70112 United States
      • Glen Burnie Maryland 21061 United States
      • Boston Massachusetts 02111 United States
      • Burlington Massachusetts 01805 United States
      • Worcester Massachusetts 01655 United States
      • Ann Arbor Michigan 48109 United States
      • Lebanon New Hampshire 03756 United States
      • Brick New Jersey 08724 United States
      • Lawrenceville New Jersey 08648 United States
      • Morristown New Jersey 07960 United States
      • Albuquerque New Mexico 87109 United States
      • Albany New York 12208 United States
      • Bronx New York 10461 United States
      • New York New York 10032 United States
      • Poughkeepsie New York 12601 United States
      • Syracuse New York 13210 United States
      • Concord North Carolina 28025 United States
      • Middleburg Heights Ohio 44130 United States
      • Oklahoma City Oklahoma 73014 United States
      • Portland Oregon 97239 United States
      • Bala-Cynwyd Pennsylvania 19004 United States
      • Bryn Mawr Pennsylvania 19010 United States
      • Pittsburgh Pennsylvania 15232 United States
      • Charleston South Carolina 29401 United States
      • Charleston South Carolina 29425 United States
      • Myrtle Beach South Carolina 29572 United States
      • Knoxville Tennessee 37909 United States
      • Dallas Texas 75231 United States
      • El Paso Texas 79920 United States
      • Houston Texas 68130 United States
      • Houston Texas 77030 United States
      • Temple Texas 76508 United States
      • Charlottesville Virginia 22908 United States
      • Richmond Virginia 23235 United States
      • Halifax Nova Scotia B3H 2Y9 Canada
      • Barrie Ontario L4M 7G1 Canada
      • Kingston Ontario K7L 3J7 Canada
      • London Ontario N6A 5W9 Canada
      • Oakville Ontario L6H 3P1 Canada
      • Toronto Ontario M4N 3M5 Canada
      • Toronto Ontario M5G 2C4 Canada
      • Toronto Ontario Canada
      • Montreal Quebec H2X 0A4 Canada
      • Montreal Quebec H4A 3J1 Canada
      • Pointe-Claire Quebec H9R 4S3 Canada
      • Sherbrooke Quebec J1E 3Z6 Canada

      View trial on ClinicalTrials.gov


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      Published June 29, 2017
    16. Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer

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      Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer


      Condition: Bladder Cancer

      Intervention:

      • Drug: Pembrolizumab
      • Drug: Cisplatin
      • Radiation: Radiotherapy

      Purpose: This study will enrol patients with maximally resected (via transurethral resection (TURBT) non-metastatic muscle invasive bladder cancer, who either wish to attempt bladder preservation therapy or are ineligible for cystectomy. Patients must have adequate organ function and performance status to receive cisplatin based chemoradiotherapy, and no contraindications to the use of pembrolizumab. The study will enrol 30 patients to be treated with pembrolizumab and radiotherapy. All patients will be planned to be treated with 64Gy of radiation therapy in 32 fractions over 6 weeks and 2 days. All patients will receive cisplatin 35mg/m2 IV concurrently weekly with radiation therapy for 6 doses total. Pembrolizumab will commence concurrently with radiation and be given 200mg IV every 21 days, continuing until the 12 week cystoscopy and assessment. Surveillance cystoscopy will be performed 12 weeks after the commencement of chemoradiotherapy, and assess the rate of complete response to therapy. A safety follow up visit will occur 4 and 12 weeks post cystoscopy. From week 31 survival follow up will commence with clinical assessment, cystoscopy and CT staging performed at intervals until 5 years. The objective of the study is to assess the safety and feasibility of combining pembrolizumab with chemoradiotherapy. The primary endpoint assessed will be safety, as defined by a satisfactorily low rate of unacceptable toxicity (G3-4 adverse events or failure of completion of planned chemotherapy and radiotherapy according to defined parameters). The secondary endpoint will be efficacy, as assessed by complete response rate of the primary tumour at first post chemoradiotherapy cystoscopic assessment. Exploratory analysis will include assessment of tumour histopathological, molecular, genetic and immunological parameters. It is expected that it will take two years to accrue the required 30 patients.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02662062

      Sponsor: Australian and New Zealand Urogenital and Prostate Cancer Trials Group

      Primary Outcome Measures:

      • Measure: Number of patients with grade 3 or 4 acute toxicities (excluding grade 3 or 4 urinary toxicities) that are related to study drug, graded according to CTCAE v4.03.
      • Time Frame: 19 weeks of treatment with Pembrolizumab
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: The efficacy of the addition of pembrolizumab to concurrent chemoradiation regimen using the best response achieved, as assessed by cystoscopy at weeks 19 and 31 of the trial (12 and 24 weeks post completion of chemoradiotherapy).
      • Time Frame: Week 19 (12 weeks post chemotherapy) and Week 31 (24 weeks post chemotherapy) where cystoscopic examinations take place.
      • Safety Issue:
      • Measure: The number of patients to develop metastatic disease (i.e. the rate of metastatic disease), as assessed by CT scan.
      • Time Frame: Through study completion, an average of 7 years.
      • Safety Issue:
      • Measure: The number of patients having a salvage cystectomy (i.e. the rate of salvage cystectomy), as assessed by cystoscopy.
      • Time Frame: Through study completion, an average of 7 years.
      • Safety Issue:

      Estimated Enrollment: 30

      Study Start Date: August 2016

      Phase: Phase 2

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • 1. Be willing and able to provide written informed consent for the trial. 2. Be 18 years of age on day of signing informed consent. 3. Have histologically-confirmed diagnosis of muscle-invasive T2-T4a, Nx or N0 urothelial cell carcinoma of the bladder. Subjects with tumors of mixed transitional/non-transitional cell histology are allowed, but transitional cell carcinoma must be the predominant histology (>50%). Subjects with predominant or exclusively non-transitional cell histology are not allowed. 4. Must have undergone maximal transurethral resection of the bladder tumour, as is judged as safe as possible by the urologist performing the resection, within 42 days of treatment. Where patient has only had a biopsy/partial resection and is otherwise eligible for entry into the study, the case should be rediscussed with the referring urologist to see whether further resection would be feasible prior to embarking with the chemo-radiotherapy. 5. Have elected not to undergo radical cystectomy, or are unsuitable for radical cystectomy. 6. Planned for chemoradiotherapy as definitive treatment. 7. Have a performance status of 0 or 1 on the ECOG Performance Scale 8. Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of registering the patient on the trial.
      • Absolute neutrophil count (ANC): ≥1.5 X 10^9/L
      • Platelets: ≥100 X 10^9/L
      • Hemoglobin: ≥9 g/dL without transfusion or EPO dependency
      • Calculated creatinine clearance ≥50 mL/min
      • Serum total bilirubin: ≤ 1.5 X ULN OR
      • Direct bilirubin ≤ ULN for participants with total bilirubin levels: > 1.5 ULN
      • AST and ALT: ≤ 2.5 X ULN
      • Albumin: >25 g/dL
      • International Normalized Ration (INR) or Prothrombin Time (PT): ≤1.5 X ULN unless participant is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants)
      • Activated Partial Thromboplastin Time (aPTT): ≤1.5 X ULN unless participant is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants) 9. Female participant of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to registering the patient. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 10. Female participants of childbearing potential should be willing to use two methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. 11. Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. 12. Willing to consent to the use of their collected tumour specimen, blood and urine as detailed in the protocol for future scientific research including but not limited to DNA, RNA and protein based biomarker detection.

      Exclusion Criteria:

      • 1. Has concurrent extra-vesical (i.e. urethra, ureter or renal pelvis) urothelial cell carcinoma of the urothelium. Patients who have involvement of the prostatic urethra with urothelial cell cancer (TCC) that was visibly completely resected and no evidence of stromal invasion of the prostate remain eligible. 2. Evidence of tumour-related moderate/severe hydronephrosis unless stented or with nephrostomy to preserve renal function. 3. Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative chemoradiotherapy. 4. Bulky T3/T4a tumours unsuitable for curative treatment (i.e. >10 cms in any dimension); node positive disease 5. Evidence of distant metastatic disease on CT chest/abdomen/pelvis performed within 42 days prior to study entry. Patients with pelvic lymph nodes deemed to be 'positive' are not eligible for the study unless histological confirmation of the largest most suspicious node is negative for malignancy. Patients with known CNS metastatic disease are excluded from the study 6. Prior pelvic radiotherapy 7. Has had prior intravenous chemotherapy, targeted small molecule therapy, or radiation therapy for treatment of bladder cancer. Prior intravesical use of BCG and mitomycin is permissible. 8. Unsuitable for concurrent cisplatin based chemoradiotherapy based on:
      • CTCAE v.4.03, Grade >2 audiometric hearing loss (25dB in two consecutive wave ranges) if previously performed.
      • CTCAE v.4.03, Grade >2 peripheral neuropathy 9. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of treatment. 10. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to registering the patient. Patients with adrenal insufficiency receiving replacement dose steroids are allowed on the trial. 11. Has a known history of active TB (Bacillus Tuberculosis) 12. Hypersensitivity to pembrolizumab or any of its excipients. 13. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 14. Prior or concurrent known additional malignancy of any site unless disease free for 5 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, Stage T1a well differentiated prostatic carcinoma in men (Gleason = 3+3, PSA <5) 15. Has any history of active autoimmune disease, Stevens-Johnson syndrome or Guillain-Barre. Exceptions to this are:
      • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone.
      • Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen who are also be eligible for this study. 16. Has known history of, or any evidence of active, non-infectious pneumonitis. 17. Has an active infection requiring systemic therapy. 18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. 19. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 20. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. 21. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 22. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 23. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). 24. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

      Contact:

      • Andrew Weickhardt, MBBS, FRACP
      • +61 3496 5763

      Locations:

      • Chris O'Brien Lifehouse
      • Camperdown New South Wales 2050 Australia
      • Prince of Wales Hospital
      • Randwick New South Wales 2013 Australia
      • Royal North Shore Hospital
      • St Leonards New South Wales 2065 Australia
      • Austin Health
      • Heidelberg Victoria 3084 Australia
      • Peter MacCallum Cancer Centre
      • Melbourne Victoria 3002 Australia
      • Sir Charles Gairdner Hospital
      • Nedlands, Perth Western Australia 6009 Australia

      View trial on ClinicalTrials.gov


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      Published February 13, 2017
    17. Phase I Dose-Escalation Study of Image-Guided Radiation Therapy for Bladder-Cancer Patients Undergoing Radiotherapy and Concurrent Gemcitabine Chemotherapy

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      Phase I Dose-Escalation Study of Image-Guided Radiation Therapy for Bladder-Cancer Patients Undergoing Radiotherapy and Concurrent Gemcitabine Chemotherapy


      Condition: Bladder Cancer

      Intervention:

      • Other: external radiation therapy with gemcitabine

      Purpose: The purpose of this study is to test the safety of different amounts (doses) of external radiation therapy (high-energy x-rays that shrink or destroy cancer) combined with chemotherapy.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT01104350

      Sponsor: Memorial Sloan Kettering Cancer Center

      Primary Outcome Measures:

      • Measure: To determine the dose limiting toxicity and establish the maximal tolerated dose
      • Time Frame: 2 years
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: To determine the complete response rate of the primary tumor
      • Time Frame: 4-6 weeks following consolidation therapy
      • Safety Issue:
      • Measure: To determine the long term toxicity
      • Time Frame: 2 years
      • Safety Issue:

      Estimated Enrollment: 19

      Study Start Date: April 2010

      Phase: Phase 1

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • MSKCC-reviewed pathologically proven diagnosis of primary bladder urothelial carcinoma without evidence of regional (nodal) or distant spread (cT1-T4a, Nx or N0).
      • Karnofsky Performance Scale (KPS) ≥ 70%
      • Age ≥18 years old
      • Adequately functioning bladder, defined as continent and without the need for an indwelling catheter
      • Absolute neutrophil count (ANC) ≥ 1500/mL; platelets ≥ 100,000/mm3 serum bilirubin < 1.5 x the upper limit of normal (ULN); aspartate aminotransferase (AST) and/alanine aminotransferase (ALT) ≤ 1.5 × ULN
      • Adequate renal function: calculated creatinine clearance > 30 mL/min/1.73 m2 using the following formula modified Cockcroft and Gault Formula for estimated Creatinine Clearance
      • Patients must be considered able to tolerate systemic chemotherapy and pelvic radiation therapy.
      • Patients must have the ability to understand and the willingness to sign a written informed consent document

      Exclusion Criteria:

      • Evidence of distant disease or histologically-proven nodal metastases. Patients with radiologic evidence of lymphadenopathy must have biopsy proof of N0 status.
      • Previous pelvic radiation therapy
      • Prior systemic chemotherapy non-cisplatin based neoadjuvant for urothelial carcinoma (prior intravesical chemotherapy or immunotherapy is permissible)
      • Prior cisplatin based neoadjuvant systemic chemotherapy for more than >4 cycles
      • Active inflammatory bowel disease (i.e., Crohn's disease or ulcerative colitis)
      • Women who are pregnant or lactating

      Locations:

      • Memorial Sloan Kettering at Basking Ridge
      • Basking Ridge New Jersey 07920 United States
      • Memorial Sloan Kettering Cancer Center @ Suffolk
      • Commack New York 11725 United States
      • Memorial Sloan Kettering Cancer Center
      • New York New York 10065 United States
      • Memorial Sloan Kettering at Mercy Medical Center
      • Rockville Centre New York United States
      • Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center
      • Sleepy Hollow New York 10591 United States
      • Memorial Sloan Kettering West Harrison
      • West Harrison New York 10604 United States

      View trial on ClinicalTrials.gov


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      Published December 12, 2016
    18. Phase I Study of Hypofractionated Radiotherapy and Anti-PD1 Antibody (Pembrolizumab) in the Treatment of Advanced Bladder Cancer

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      Phase I Study of Hypofractionated Radiotherapy and Anti-PD1 Antibody (Pembrolizumab) in the Treatment of Advanced Bladder Cancer


      Condition: Invasive Bladder Cancer

      Intervention:

      • Drug: Pembrolizumab
      • Radiation: Radiotherapy

      Purpose: PLUMMB is an phase I trial to investigate the safety, tolerability and effectiveness of an immunotherapy drug called Pembrolizumab used in combination with radiotherapy. The study will also investigate two different doses of pembrolizumab, starting at 100mg (through an intravenous drip) and increasing to 200mg for the next cohort of patients, if the first dose is well tolerated. The patients suitable for this study will be: Group A those with locally advanced bladder cancer or Group B patients whose cancer has spread from the bladder (metastatic bladder cancer). Treatment in the PLUMMB trial will start with a pembrolizumab 2 weeks prior to starting a course of 4 - 6 weeks radiotherapy. Treatment with pembrolizumab will then be given every three weeks. Patients in Group A will then continue to take pembrolizumab for up to a year unless they have disease progression or unacceptable side effects in the meantime. Patients in Group B will continue taking pembrolizumab for as long as needed until they have disease progression or unacceptable side effects. Patients will be seen every 3 weeks during treatment and every 3-6 months thereafter. CT scans will be done every 3 months during treatment and as per usual care (usually 6 monthly) after the treatment has finished. Patients in Group A will also have a cystoscopy (camera test) to look into the bladder 3 months after they finish radiotherapy. This is standard care and would be the same for patients not on a research study.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02560636

      Sponsor: Royal Marsden NHS Foundation Trust

      Primary Outcome Measures:

      • Measure: Establishing the maximum tolerated dose (MTD)
      • Time Frame: up to 36 months
      • Safety Issue:
      • Measure: Measurement of the rates of toxicity
      • Time Frame: 6 weeks after the last fraction of radiotherapy has been administered
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Measurement of the percentage of patients experiencing late grade 2+ and 3+ toxicity
      • Time Frame: 6 weeks and one day following the completion of radiotherapy until the 28 days after the patients last dose of Pembrolizumab
      • Safety Issue:
      • Measure: Measuring rates of tumour response to treatment.
      • Time Frame: 3 months after completion of radiotherapy
      • Safety Issue:
      • Measure: Measurement of progression free and overall survival rate
      • Time Frame: Long term survival followup (reported at 2 years)
      • Safety Issue:

      Estimated Enrollment: 34

      Study Start Date: June 2016

      Phase: Phase 1

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      1. Histologically confirmed invasive bladder.carcinoma (T2-4,N0-3,M0-1).
      2. Be willing and able to provide written informed consent for the trial.
      3. Be ≥ 18 years of age on day of signing informed consent.
      4. Have measurable disease based on RECIST 1.
      5. , or, in group A, disease assessable by cystoscopic assessment.
      6. Have consented to analysis of tissue from an archival tissue sample
      7. Have a performance status of 0-1 on the ECOG Performance Scale.
      8. Planned for hypofractionated radiotherapy
      9. Demonstrate adequate organ function as defined in table 2 (please see protocol) all screening blood tests should be performed within 10 days of confirmation of eligibility.
      10. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to confirmation of study eligibility. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
      11. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
      12. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy if their partner has childbearing potential (as defined by not being surgically sterilized or have not been free from menses for > 1 year).

      Exclusion Criteria:

      • The subject must be excluded from participating in the trial if the subject: 1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment. 2. Previous pelvic radiotherapy, history of inflammatory bowel disease or other conditions that would in the opinion of the investigator would preclude the safe administration of pelvic radiotherapy. 3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (>dose equivalent to 10mg of Prednisolone/day) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 4. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 5. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent or therapy.
      • Note: Subjects with ≤ Grade 2 neuropathy or chemotherapy induced alopecia/nail changes are an exception to this criterion and may qualify for the study.
      • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 6. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, localized prostate cancer (≤T2 ≤ Gl3+4) or in situ cervical cancer that has undergone potentially curative therapy. Patients may have received treatment for previous urothelial malignancy. 7. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. 8. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study. 9. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 10. Has an active infection requiring systemic therapy. 11. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 13. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. 14. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). 15. Has a known history of Human Immunodeficiency Virus (HIV). 16. Has known clinical history of Hepatitis B or Hepatitis C . 17. Has received a live vaccine within 30 days prior to the first dose of trial treatment.

      Contact:

      • Sarah Webb
      • +44 (0) 20 8915 6508

      Locations:

      • NIHR Biomedical Research Centre at RM and ICR (https://www.cancerbrc.org/)
      • London SW3 6JJ United Kingdom
      • NIHR Biomedical Research Centre at RM and ICR (https://www.cancerbrc.org/)
      • Sutton SM2 5PT United Kingdom

      View trial on ClinicalTrials.gov


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      Published June 29, 2017
    19. Phase Ib/II Study of Neoadjuvant Pembrolizumab With Gemcitabine-Cisplatin (Cisplatin-Eligible) or Gemcitabine (Cisplatin-Ineligible) in Subjects With T2-4aN0M0 Urothelial Cancer: HCRN GU14-188

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      Phase Ib/II Study of Neoadjuvant Pembrolizumab With Gemcitabine-Cisplatin (Cisplatin-Eligible) or Gemcitabine (Cisplatin-Ineligible) in Subjects With T2-4aN0M0 Urothelial Cancer: HCRN GU14-188


      Condition: Urothelial Carcinoma, Bladder Cancer

      Intervention:

      • Drug: Pembrolizumab
      • Drug: Gemcitabine
      • Drug: Cisplatin
      • Procedure: Consolidative Surgery

      Purpose: This is a pre-surgical study involving subjects with muscle invasive bladder cancer, or urothelial cancer, who are candidates for neoadjuvant therapy. It is is a two-part trial with a one-arm phase Ib portion followed by a two-arm phase II portion. The study treatment is stratified into two cohorts based on cisplatin eligibility.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02365766

      Sponsor: Christopher Hoimes, M.D.

      Primary Outcome Measures:

      • Measure: Phase Ib: Number of Patients with Adverse Events as a Measure of Safety and Tolerability
      • Time Frame: C1D1 and every 21 days thereafter while on treatment (up to 4 months)
      • Safety Issue:
      • Measure: Phase II: Rate of Pathologic Muscle Invasive Response (PaIR)
      • Time Frame: Within 2-7 weeks post last dose of pembrolizumab (up to 6 months)
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Relapse-Free Survival (RFS)
      • Time Frame: Up to 18 months
      • Safety Issue:
      • Measure: Overall Survival (OS)
      • Time Frame: From date of registration to date of death (up to 5 years)
      • Safety Issue:
      • Measure: Radical Cystectomy (RC) Rate
      • Time Frame: Within 2-7 weeks post last dose of pembrolizumab (up to 6 months)
      • Safety Issue:

      Estimated Enrollment: 81

      Study Start Date: May 2015

      Phase: Phase 1/Phase 2

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • Be willing and able to provide written informed consent for the trial.
      • Over 18 years of age on day of signing informed consent.
      • Have histologically confirmed muscle invasive disease of the urinary bladder, renal pelvis, or ureters.
      • Histology must be urothelial carcinoma (transitional cell carcinoma) or urothelial carcinoma with mixed histology/features.
      • Clinical stage cT2-4aN0M0. Please see exclusion criteria for acceptable N0 determination/lymph node size.
      • Have a surgical evaluation that documents the plan for multimodality therapy with a consolidative radical cystectomy or nephroureterectomy. NOTE on surgical intent: Criteria for acceptable surgical risk are not defined and per treating urologist. Minimum guidance on surgical intent includes subjects who do not have significant cardiovascular disease such as NHYA class III or IV heart failure, unstable arrhythmias or angina, active CAD, and/or EF<25%. Specific diagnostic testing to determine surgical intent is not required and per treating urologist or oncologist discretion.
      • Have an archived tumor block available to submit unstained slides for PD-L1 expression, basal and luminal subtype analysis; MANDATORY. If slides are not available, a biopsy is strongly encouraged to obtain tissue for submission
      • Subjects on full dose anticoagulants must be on a stable regimen of warfarin or low molecular weight heparin (LMWH) for at least two weeks.
      • Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to study registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required.
      • Female subjects of childbearing potential must be willing to use 2 methods of birth control, be surgically sterile, or abstain from heterosexual intercourse for the course of the study and through 120 days after the last dose of study medication. NOTE: Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
      • Male subjects must agree to use a barrier method of male contraception starting with the first dose of study therapy and through 120 days after the last dose of study therapy. COHORT I
      • CISPLATIN-ELIGIBLE: In addition to the inclusion criteria listed above, Cohort I subjects must satisfy all of the following criteria:
      • Glomerular filtration rate (GFR) or creatinine clearance (Ccr) ≥ 50 mL/min. (24 hour urine preferred). The cisplatin dose will be split over two days for values between 50-59 mL/min
      • ECOG PS 0, 1 (and not 2)
      • Hearing impaired ≤ grade 1 (may or may not be enrolled in a monitoring program)
      • Peripheral neuropathy ≤grade 1 COHORT II
      • CISPLATIN-INELIGIBLE: In addition to the inclusion criteria listed above, Cohort II subjects must also meet any ONE of the following criteria:
      • GFR or Ccr: 30-49 (24 hour urine preferred).
      • ECOG PS 2
      • Hearing impaired ≥grade 2 as assessed by treating physician (may or may not be enrolled in a monitoring program).
      • Peripheral neuropathy of Grade 2-4

      Exclusion Criteria:

      • for acceptable N0 determination/lymph node size.
      • Have a surgical evaluation that documents the plan for multimodality therapy with a consolidative radical cystectomy or nephroureterectomy. NOTE on surgical intent: Criteria for acceptable surgical risk are not defined and per treating urologist. Minimum guidance on surgical intent includes subjects who do not have significant cardiovascular disease such as NHYA class III or IV heart failure, unstable arrhythmias or angina, active CAD, and/or EF<25%. Specific diagnostic testing to determine surgical intent is not required and per treating urologist or oncologist discretion.
      • Have an archived tumor block available to submit unstained slides for PD-L1 expression, basal and luminal subtype analysis; MANDATORY. If slides are not available, a biopsy is strongly encouraged to obtain tissue for submission
      • Subjects on full dose anticoagulants must be on a stable regimen of warfarin or low molecular weight heparin (LMWH) for at least two weeks.
      • Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to study registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required.
      • Female subjects of childbearing potential must be willing to use 2 methods of birth control, be surgically sterile, or abstain from heterosexual intercourse for the course of the study and through 120 days after the last dose of study medication. NOTE: Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
      • Male subjects must agree to use a barrier method of male contraception starting with the first dose of study therapy and through 120 days after the last dose of study therapy. COHORT I
      • CISPLATIN-ELIGIBLE: In addition to the inclusion criteria listed above, Cohort I subjects must satisfy all of the following criteria:
      • Glomerular filtration rate (GFR) or creatinine clearance (Ccr) ≥ 50 mL/min. (24 hour urine preferred). The cisplatin dose will be split over two days for values between 50-59 mL/min
      • ECOG PS 0, 1 (and not 2)
      • Hearing impaired ≤ grade 1 (may or may not be enrolled in a monitoring program)
      • Peripheral neuropathy ≤grade 1 COHORT II
      • CISPLATIN-INELIGIBLE: In addition to the inclusion criteria listed above, Cohort II subjects must also meet any ONE of the following criteria:
      • GFR or Ccr: 30-49 (24 hour urine preferred).
      • ECOG PS 2
      • Hearing impaired ≥grade 2 as assessed by treating physician (may or may not be enrolled in a monitoring program).
      • Peripheral neuropathy of Grade 2-4 Exclusion Criteria: Subjects may not have any of the following:
      • A non-surgical approach recommended by the treating urologist due to any reason. Criteria for surgical intent are not defined and, rather, suitability is determined and documented by the subject's treating urologist. Minimum guidance on surgical intent includes subjects who do not have significant cardiovascular disease such as NHYA class III or IV heart failure, unstable arrhythmias or angina, active CAD, and/or EF<25%. Specific cardiopulmonary diagnostic testing to determine surgical intent is not required and per treating urologist or oncologist discretion.
      • Has abdomino-pelvic short axis lymph node of ≥15mm without biopsy. NOTE: A subject with a staging biopsy proving a non-neoplastic process/N0 will meet inclusion.
      • Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 28 days prior to study registration.
      • Has a diagnosis of immunodeficiency or received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study registration. Subjects on steroids for physiologic replacement due to a non-cancer related cause would not be excluded.
      • Has had a prior monoclonal antibody ≤ 28 days prior to study registration or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 28 days earlier.
      • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy for urothelial carcinoma.
      • Has a known additional malignancy that is progressing or required treatment ≤ 48 months of study registration. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer that has undergone potentially curative therapy, stable (as defined by PSA change, checked within 30 days) and untreated very low-risk or low-risk prostate cancer defined by current NCCN guidelines.
      • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Brain imaging is not required and per discretion of treating physician.
      • Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. NOTE: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.
      • Has known evidence of interstitial lung disease or active, non-infectious pneumonitis.
      • Has an active infection requiring systemic therapy.
      • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
      • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
      • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
      • Has received therapy with hematopoietic growth factor such as G-CSF or GM-CSF in the 14 days prior to registration.
      • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
      • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
      • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
      • Has received a live vaccine within 30 days prior to the first dose of trial treatment. NOTE: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccines. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

      Contact:

      • Christopher Hoimes, M.D.
      • (216) 844-3951

      Locations:

      • Indiana University Melvin and Bren Simon Cancer Center
      • Indianapolis Indiana 46202 United States
      • IU Health Central Indiana Cancer Center
      • Indianapolis Indiana 46219 United States
      • Community Regional Cancer Care
      • Indianapolis Indiana 46256 United States
      • St. Vincent Hospital
      • Indianapolis Indiana 46260 United States
      • Washington University: Siteman Cancer Center
      • Saint Louis Missouri 63110 United States
      • University of New Mexico Cancer Center
      • Albuquerque New Mexico 87106 United States
      • University Hospitals Seidman Cancer Center
      • Cleveland Ohio 44106 United States
      • Thomas Jefferson University: Kimmel Cancer Center
      • Philadelphia Pennsylvania 19107 United States
      • Virginia Oncology Associates
      • Norfolk Virginia 23502 United States

      View trial on ClinicalTrials.gov


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      Published June 29, 2017
    20. Phase II Single Arm Study of Gemcitabine and Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Prior to Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer

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      Phase II Single Arm Study of Gemcitabine and Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Prior to Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer


      Condition: Bladder Cancer

      Intervention:

      • Drug: pembrolizumab, gemcitabine and cisplatin

      Purpose: The purpose of this study is to evaluate whether adding pembrolizumab (Keytruda) to the combination of gemcitabine and cisplatin will improve shrinkage of the tumor before having a cystectomy, for people with muscle-invasive bladder cancer (MIBC).

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02690558

      Sponsor: UNC Lineberger Comprehensive Cancer Center

      Primary Outcome Measures:

      • Measure: Number of subjects that reach pathological downstaging to
      • Time Frame: 14 weeks of treatment plus cystectomy within 70 days after treatment
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Number of subjects that reach complete pathologic response (pT0) defined as pT0N0M0 at the time of cystectomy
      • Time Frame: 14 weeks of treatment plus cystectomy within 70 days of treatment
      • Safety Issue:
      • Measure: Event Free Survival
      • Time Frame: 14 weeks of treatment plus 5 years of followup
      • Safety Issue:
      • Measure: Overall survival
      • Time Frame: 14 weeks of treatment plus 3 years or until death
      • Safety Issue:
      • Measure: Number of adverse events and severity by grade (CTCAE).
      • Time Frame: 14 weeks of treatment plus 30 days for toxicity followup
      • Safety Issue:

      Estimated Enrollment: 39

      Study Start Date: May 2016

      Phase: Phase 2

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • Be able to give written IRB approved informed consent and be able to follow protocol requirements.
      • Be greater than or equal to 18 years of age on day of signing informed consent.
      • Has a performance status of 0 or 1 on the ECOG Performance Scale
      • Has histologically confirmed urothelial carcinoma of the bladder; those with mixed histology, including a component of urothelial carcinoma, are eligible. Pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded.
      • Has clinical stage T2-T4a N0/X M0 urothelial carcinoma. Clinical T stage is based on the pre-study standard of care transurethral resection of the bladder tumor (TURBT) sample and imaging studies.
      • Has staging scans with abdominal/pelvic CT or MRI scan and CT scan or x-ray of the chest within 4 weeks prior to treatment initiation
      • Be a medically appropriate candidate for radical cystectomy as determined by an attending urologist and be planning to receive cystectomy.
      • Has had no prior systemic cytotoxic chemotherapy for urothelial carcinoma (prior intravesicular chemotherapies are permitted)
      • Patients must have tumor tissue from transurethral resection of the bladder tumor (TURBT) available for submission that is sufficient for correlative testing, and agree to submission of a paraffin block or 20 formalin-fixed paraffin embedded (FFPE) slides of 5-10 microns in thickness. Patients must also agree to submission of tissue from cystectomy.
      • Demonstrate adequate organ function as defined in the table below; all screening labs should be performed within 10 days of treatment initiation. Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) Renal Serum creatinine OR Measured or calculated creatinine clearance (CrCL; GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (Creatinine clearance should be calculated per CKD-EPI equation.) Hepatic Serum total bilirubin ≤ 1.5 X ULN (≤ 3 X ULN if Gilbert's Syndrome) OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy. If subject receiving anticoagulants, PT or PTT should be within therapeutic range of intended use of anticoagulants
      • Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of pembrolizumab.
      • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. The two birth control methods can be composed of: two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. Subjects should start using birth control from the screening visit and continue throughout the study period up to 120 days after the last dose of study therapy. The following are considered adequate barrier methods of contraception: diaphragm, condom (by the partner), copper intrauterine device, sponge, or spermicide. Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents).
      • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
      • Life expectancy greater than 3 months
      • Consents to whole blood collection prior to initiating therapy and at cystectomy for support of correlative research studies

      Exclusion Criteria:

      • The subject must be excluded from participating in the trial if the subject meets any of the following:
      • Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of pembrolizumab.
      • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. NOTE: see exception to use of systemic steroid as prophylactic anti-emetic prior to cisplatin in section 4.2.2. Inhaled and topical steroids are allowed.
      • Has a known history of active TB (Bacillus Tuberculosis)
      • Hypersensitivity to pembrolizumab or any of its excipients.
      • Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
      • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
      • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
      • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
      • Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
      • Has an active infection requiring systemic therapy
      • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
      • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
      • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
      • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
      • Has received prior radiation therapy to the bladder for the purpose of treating urothelial carcinoma
      • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
      • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
      • Has clinically relevant hearing impairment > Grade 2
      • Has received a live vaccine within 30 days prior to the first dose of trial treatment

      Contact:

      • Rachel Munoz, RN
      • 919-966-4432

      Locations:

      • North Carolina Cancer Hospital (UNC)
      • Chapel Hill North Carolina 27599 United States
      • Duke University Medical Center
      • Durham North Carolina 27710 United States

      View trial on ClinicalTrials.gov


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      Published June 29, 2017
    21. Phase II Study to Evaluate the Response to 2 Induction Courses (12 Intravesical Instillations) of Bacillus Calmette-Guérin (BCG) for High Risk Superficial Bladder Cancer

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      Phase II Study to Evaluate the Response to 2 Induction Courses (12 Intravesical Instillations) of Bacillus Calmette-Guérin (BCG) for High Risk Superficial Bladder Cancer


      Condition: Bladder Cancer, High Risk Superficial

      Intervention:

      • Biological: Bacillus Calmette-Guérin (BCG)

      Purpose: This is a phase II study. This means that BCG therapy has already been found to be safe in humans. The investigators just want to see if using more treatments works better.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02281383

      Sponsor: Memorial Sloan Kettering Cancer Center

      Primary Outcome Measures:

      • Measure: response rate
      • Time Frame: 1 year
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: proportion of patients who progress to muscle invasive
      • Time Frame: 6 months after BCG
      • Safety Issue:

      Estimated Enrollment: 90

      Study Start Date: October 2014

      Phase: Phase 2

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • Patients must have high risk non-muscle invasive urothelial bladder carcinoma (Tis, TaHG, or T1) that is pathologically confirmed by the Memorial Sloan Kettering Department of Pathology or a documented history of TaHG or T1 non-muscle invasive urothelial bladder tumors.
      • 18 years and older
      • All visible papillary lesions must be macroscopically resected within 60 days of treatment initiation.
      • Absence of urothelial carcinoma involving the upper urinary tract (documented by radiological imaging or biopsy) preferably within 12 months from the start of treatment. Should the imaging or biopsy be performed outside this window it will be up to the physicians discretion to re-scan/biopsy.
      • Patients who have received a single dose of mitomycin C following staging TUR.

      Exclusion Criteria:

      • Currently being treated or scheduled to have radiation treatment for bladder cancer during the study.
      • Treatment with intravesical BCG or chemotherapy for a patient's current
      • Currently being treated or scheduled to have treatment with any systemic or intravesical chemotherapeutic agent during the study.
      • Currently being treated with or having been treated in the last 12 months with any investigational drug for high risk superficial bladder cancer.
      • Previous muscle-invasive (i.e., stage T2 or higher) transitional cell carcinoma of the bladder.
      • Currently being treated for metastatic transitional cell carcinoma.
      • Scheduled to have surgery for bladder cancer during the study.
      • Presence of clinically significant infections or congenital or acquired immunodeficiency.

      Contact:

      • Harry W. Herr, MD
      • 646-422-4411

      Locations:

      • Memoral Sloan Kettering Cancer Center
      • Basking Ridge New Jersey United States
      • Memorial Sloan Kettering Monmouth
      • Middletown New Jersey 07748 United States
      • Memorial Sloan Kettering Commack
      • Commack New York 11725 United States
      • Memorial Sloan Kettering Westchester
      • Harrison New York 10604 United States
      • Memorial Sloan Kettering Cancer Center
      • New York New York 10065 United States

      View trial on ClinicalTrials.gov


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      Published June 29, 2017
    22. Phase II Trial of Atezolizumab in BCG-Unresponsive Non-muscle Invasive Bladder Cancer

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      Phase II Trial of Atezolizumab in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer


      Condition: Recurrent Bladder Urothelial Carcinoma, Stage 0a Bladder Urothelial Carcinoma AJCC v6 and v7, Stage 0is Bladder Urothelial Carcinoma AJCC v6 and v7, Stage I Bladder Urothelial Carcinoma AJCC v6 and v7

      Intervention:

      • Drug: Atezolizumab

      Purpose: This phase II trial studies how well atezolizumab works in treating patients with non-muscle invasive bladder cancer that has come back and has not responded to treatment with Bacillus Calmette-Guerin (BCG). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02844816

      Sponsor: National Cancer Institute (NCI)

      Primary Outcome Measures:

      • Measure: Complete response (CR) rate in the subset of patients with carcinoma in situ (CIS) based on biopsy
      • Time Frame: At 25 weeks
      • Safety Issue:
      • Measure: Event-free survival (EFS)
      • Time Frame: From date of registration to first documentation of event, assessed up to 18 months
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Event-free survival (EFS) in the Ta/T1 subset
      • Time Frame: 18 months
      • Safety Issue:
      • Measure: Progression-free survival (PFS)
      • Time Frame: From time of registration to time of first documentation progression or death due to any cause, assessed up to 5 years
      • Safety Issue:
      • Measure: Cystectomy-free survival
      • Time Frame: Up to 5 years
      • Safety Issue:
      • Measure: Bladder cancer specific survival
      • Time Frame: From date of registration to date of death due to bladder cancer, assessed up to 5 years
      • Safety Issue:
      • Measure: Overall survival
      • Time Frame: From date of registration to date of death due to any cause, assessed up to 5 years
      • Safety Issue:
      • Measure: Incidence of adverse events
      • Time Frame: Up to 18 months
      • Safety Issue:

      Estimated Enrollment: 162

      Study Start Date: February 7, 2017

      Phase: Phase 2

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • Patients must have histologically proven, recurrent, non-muscle invasive urothelial carcinoma of the bladder within 60 days prior to registration; the carcinoma must be stage T1 high-grade, stage CIS, or stage Ta high-grade
      • Patients with mixed urothelial carcinoma and a glandular and/or squamous component will be eligible for the trial, but the presence of other histologic variants, pure adenocarcinoma, or pure squamous cell carcinoma, or pure squamous carcinoma in situ will make a patient ineligible
      • Patients must have had all visible tumor resected completely within 60 days prior to registration; CIS disease is not expected to be completely excised; all patients must have tumor tissue from the histologic diagnosis of recurrence available for central pathology review submission; failure to submit these materials will make the patient ineligible for this study
      • Patients must have had cystoscopy confirming no visible papillary tumor within 21 days prior to registration; (CIS disease is not expected to have been completely excised); if the transurethral resection of bladder tumor (TURBT) or bladder biopsy falls within 21 days of registration it will fulfill this criterion
      • Patients must have had urine cytology within 21 days prior to registration; cytology for patients with CIS component is not expected to be negative for malignant cells; if the cytology for male patients with only Ta/T1 disease in the absence of CIS is positive for malignant cells, patient must have had a biopsy of the prostatic urethra within the previous six months
      • All patients with T1 urothelial carcinoma at study entry must undergo re-TURBT within 60 days prior to registration, and must have evidence of uninvolved muscularis propria in the pathologic specimen from either the first or the second TURBT; tissue from the re-resection must be submitted for central review in addition to the tissue from the first TURBT; the TURBT that identified the recurrent T1 disease may have taken place more than 60 days prior to registration but not more than 120 days; patients with high grade Ta or CIS do not require a re-TURBT, but if this is performed at the discretion of the treating physician, the second TURBT must be within 60 days of registration; there is no requirement for muscularis propria in the specimen of Ta/CIS patients, but the tissue from the first and second TURBTs must be submitted for central review; if a patient with Ta/T1 disease undergoes repeat TURBT, the patient will be stratified as having CIS if there is CIS on either TURBT
      • Patients must not have had urothelial carcinoma in the prostatic urethra within the previous 24 months or muscle invasive urothelial carcinoma of the bladder at any time; patients with prior urothelial carcinoma in the upper urinary tract within the previous 24 months will only be eligible if they had =< T1 carcinoma and were treated with nephroureterectomy; patients must have a computed tomography (CT) or magnetic resonance imaging (MRI) (including CT-intravenous pyelogram [IVP], CT-urogram or MR-urogram) of the abdomen and pelvis to rule out upper tract malignancy and intra-abdominal metastases within 90 days prior to registration; if a patient cannot tolerate intravenous contrast, a retrograde pyelogram should be performed within 90 days prior to registration
      • Patients must be deemed unfit for radical cystectomy by the treating physician, or the patient must refuse radical cystectomy, which is considered standard of care for these patients; the reason for patients not to undergo cystectomy will be clearly documented
      • Patients must be BCG-unresponsive; a patient is BCG-unresponsive if they meet one or more of the following criteria:
      • Patient has persistent or recurrent high-grade Ta/CIS urothelial carcinoma after completing therapy with at least induction BCG (>= 5 doses) and first round maintenance (>= 2 doses) or second induction BCG (>= 2 doses); both rounds of BCG must have been administered within a 12 month period; these patients must have either had high-grade Ta tumors and did not achieve a disease-free state for more than 6 months following last dose of BCG, or they had CIS and did not achieve a CR; S1605 registration must occur within 9 months of the last dose of BCG.
      • If a patient does not meet these criteria only because the last dose of BCG was more than 9 months ago, the patient may become eligible if he/she shows histologically proven high-grade recurrence after an additional round of induction or maintenance BCG (>= 3 doses) within 9 months prior to registration
      • Patient has persistent or recurrent high grade T1 urothelial carcinoma after completing therapy with at least induction BCG (>= 5 doses); patients with recurrent high grade T1 urothelial carcinoma after additional rounds of BCG will also be eligible, but one round of maintenance therapy or a second induction is not a pre-requisite for these patients. Trial registration must occur within 9 months of the last dose of BCG
      • If a patient does not meet these criteria only because the last dose of BCG was more than 9 months ago, the patient may become eligible if he/she shows histologically proven high grade recurrence after an additional round of induction or maintenance BCG (>= 3 doses) within 9 months prior to registration
      • Patient achieves disease-free state at 6 month time point (i.e., complete response; presence of only low-grade tumor at this timepoint is still considered complete response) after induction and maintenance (or second round of induction) BCG but later experiences a high-grade Ta/T1recurrence (with or without concomitant CIS) within 6 months after the last dose of BCG or recurrent CIS (in absence of concomitant Ta/T1 tumor) within 12 months after the last BCG dose; the time of eligibility is measured from the last dose of BCG to the time of disease recurrence; the patient must be registered on the trial within 60 days of this recurrence, or within 60 days of a re-TURBT if indicated
      • All adverse events associated with any prior surgery and intravesical therapy must have resolved to grade =< 2 prior to registration
      • Patients must not have had prior systemic chemotherapy for bladder cancer or systemic immunotherapy, including, but not limited to interferon alfa-2b, high dose interleukin 2 (IL-2), pegylated interferon (PEG-IFN), PD-1, anti-PD-L1, intra-tumoral; patients must not have had vaccine therapies within 6 weeks prior to registration; patients must not have received or be planning to receive any of the prohibited therapies during protocol treatment; prior intravesical administration of chemotherapy, interferon, Vicinium (VB4-485), BC-819 or Instiladrin (rAd-interferon-alpha/Syn3) is allowed if all other criteria are met and the last administration was >= 30 days before registration
      • Patients must not be planning to receive concomitant other biologic therapy, radiation therapy, intravesical chemotherapy, surgery, or other anti-cancer therapy while on this protocol
      • Patients must not have received any prior radiation to the bladder for bladder cancer
      • Patients must not have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 4 weeks prior to registration; exceptions: (1) patients may have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea); (2) the use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
      • Patients must not have received a live, attenuated vaccine within 4 weeks before registration or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of atezolizumab
      • Influenza vaccination should be given during influenza season only (approximately October to March); patients must not receive live, attenuated influenza vaccine within 4 weeks prior to cycle 1, day 1 or at any time during the study
      • Patients must not require treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumab
      • Absolute neutrophil count (ANC) >= 1,500 microliter (mcL) (within 42 days prior to registration)
      • Platelets >= 100,000/mcL (within 42 days prior to registration)
      • Hemoglobin >= 9 g/dL (within 42 days prior to registration)
      • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL) (within 42 days prior to registration)
      • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2 x IULN (within 42 days prior to registration)
      • Serum creatinine =< 1.5 ULN OR measured or calculated creatinine clearance >= 30 mL/min (within 42 days prior to registration)
      • Patients must have Zubrod performance status =< 2
      • Patients must have a baseline electrocardiograph (ECG) performed within 42 days prior to registration
      • Patient must not have history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis
      • Patients must not have an active infection requiring oral or IV antibiotics within 14 days prior to registration; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
      • Patients must not have severe infections within 28 days prior to registration, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
      • Patients must not have active autoimmune disease that has required systemic treatment in past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; autoimmune diseases include, but are not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
      • Patients must not have undergone prior allogeneic bone marrow transplantation or prior solid organ transplantation
      • Patient must not have active tuberculosis
      • Patients must not have active hepatitis B (chronic or acute) or active hepatitis C infection
      • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible
      • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
      • Patients positive for human immunodeficiency virus (HIV) are eligible only if they have all of the following:
      • A stable regimen of highly active anti-retroviral therapy (HAART)
      • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
      • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests
      • No other prior malignancy is allowed except, for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
      • Patients must not be pregnant or nursing due to the potential teratogenic side effects of the protocol treatment; administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
      • Due to the potential drug reaction with atezolizumab, patients must not be known to be allergic to Chinese hamster egg or ovaries
      • Patients must be offered the opportunity to participate in specimen banking for future studies, to include translational medicine studies
      • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
      • As a part of the oncology patient enrollment network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

      Locations:

      • Southern Cancer Center PC-Daphne
      • Daphne Alabama 36526 United States
      • Southern Cancer Center PC-Mobile
      • Mobile Alabama 36607 United States
      • Southern Cancer Center PC-Providence
      • Mobile Alabama 36608 United States
      • Southern Cancer Center PC-Springhill
      • Mobile Alabama 36608 United States
      • Mayo Clinic in Arizona
      • Scottsdale Arizona 85259 United States
      • University of Arizona Cancer Center-Orange Grove Campus
      • Tucson Arizona 85704 United States
      • Banner University Medical Center - Tucson
      • Tucson Arizona 85719 United States
      • University of Arizona Cancer Center-North Campus
      • Tucson Arizona 85719 United States
      • John L McClellan Memorial Veterans Hospital
      • Little Rock Arkansas 72205 United States
      • UC San Diego Moores Cancer Center
      • La Jolla California 92093 United States
      • Los Angeles County-USC Medical Center
      • Los Angeles California 90033 United States
      • USC / Norris Comprehensive Cancer Center
      • Los Angeles California 90033 United States
      • Stanford Cancer Institute Palo Alto
      • Palo Alto California 94304 United States
      • Eisenhower Medical Center
      • Rancho Mirage California 92270 United States
      • University of California Davis Comprehensive Cancer Center
      • Sacramento California 95817 United States
      • UCSF Medical Center-Mission Bay
      • San Francisco California 94158 United States
      • University of Colorado Hospital
      • Aurora Colorado 80045 United States
      • Kaiser Permanente-Franklin
      • Denver Colorado 80205 United States
      • Kaiser Permanente-Rock Creek
      • Lafayette Colorado 80026 United States
      • Kaiser Permanente-Lone Tree
      • Lone Tree Colorado 80124 United States
      • Greenwich Hospital
      • Greenwich Connecticut 06830 United States
      • Yale University
      • New Haven Connecticut 06520 United States
      • Veterans Affairs Connecticut Healthcare System-West Haven Campus
      • West Haven Connecticut 06516 United States
      • Delaware Clinical and Laboratory Physicians PA
      • Newark Delaware 19713 United States
      • Helen F Graham Cancer Center
      • Newark Delaware 19713 United States
      • Medical Oncology Hematology Consultants PA
      • Newark Delaware 19713 United States
      • Regional Hematology and Oncology PA
      • Newark Delaware 19713 United States
      • Christiana Care Health System-Christiana Hospital
      • Newark Delaware 19718 United States
      • Christiana Care Health System-Wilmington Hospital
      • Wilmington Delaware 19801 United States
      • MedStar Washington Hospital Center
      • Washington District of Columbia 20010 United States
      • George Washington University Medical Center
      • Washington District of Columbia 20037 United States
      • Mount Sinai Comprehensive Cancer Center at Aventura
      • Aventura Florida 33180 United States
      • University of Florida Health Science Center - Gainesville
      • Gainesville Florida 32610 United States
      • Mount Sinai Medical Center
      • Miami Beach Florida 33140 United States
      • Indian River Medical Center
      • Vero Beach Florida 32960 United States
      • Emory University Hospital/Winship Cancer Institute
      • Atlanta Georgia 30322 United States
      • Atlanta VA Medical Center
      • Decatur Georgia 30033 United States
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
      • Savannah Georgia 31405 United States
      • Pali Momi Medical Center
      • 'Aiea Hawaii 96701 United States
      • Hawaii Cancer Care Inc-POB II
      • Honolulu Hawaii 96813 United States
      • Hawaii Oncology Inc-POB I
      • Honolulu Hawaii 96813 United States
      • Island Urology
      • Honolulu Hawaii 96813 United States
      • Queen's Medical Center
      • Honolulu Hawaii 96813 United States
      • Straub Clinic and Hospital
      • Honolulu Hawaii 96813 United States
      • University of Hawaii Cancer Center
      • Honolulu Hawaii 96813 United States
      • Hawaii Oncology Inc-Kuakini
      • Honolulu Hawaii 96817 United States
      • Kapiolani Medical Center for Women and Children
      • Honolulu Hawaii 96826 United States
      • Saint Alphonsus Cancer Care Center-Boise
      • Boise Idaho 83706 United States
      • Saint Luke's Mountain States Tumor Institute
      • Boise Idaho 83712 United States
      • Saint Alphonsus Cancer Care Center-Caldwell
      • Caldwell Idaho 83605 United States
      • Walter Knox Memorial Hospital
      • Emmett Idaho 83617 United States
      • Idaho Urologic Institute-Meridian
      • Meridian Idaho 83642 United States
      • Saint Luke's Mountain States Tumor Institute - Meridian
      • Meridian Idaho 83642 United States
      • Saint Alphonsus Medical Center-Nampa
      • Nampa Idaho 83686 United States
      • Saint Luke's Mountain States Tumor Institute-Twin Falls
      • Twin Falls Idaho 83301 United States
      • Rush - Copley Medical Center
      • Aurora Illinois 60504 United States
      • Illinois CancerCare-Bloomington
      • Bloomington Illinois 61704 United States
      • Illinois CancerCare-Canton
      • Canton Illinois 61520 United States
      • Illinois CancerCare-Carthage
      • Carthage Illinois 62321 United States
      • Centralia Oncology Clinic
      • Centralia Illinois 62801 United States
      • Northwestern University
      • Chicago Illinois 60611 United States
      • Carle on Vermilion
      • Danville Illinois 61832 United States
      • Cancer Care Specialists of Illinois - Decatur
      • Decatur Illinois 62526 United States
      • Decatur Memorial Hospital
      • Decatur Illinois 62526 United States
      • Carle Physician Group-Effingham
      • Effingham Illinois 62401 United States
      • Crossroads Cancer Center
      • Effingham Illinois 62401 United States
      • Elmhurst Memorial Hospital
      • Elmhurst Illinois 60126 United States
      • Illinois CancerCare-Eureka
      • Eureka Illinois 61530 United States
      • Illinois CancerCare-Galesburg
      • Galesburg Illinois 61401 United States
      • Edward Hines Jr VA Hospital
      • Hines Illinois 60141 United States
      • Illinois CancerCare-Kewanee Clinic
      • Kewanee Illinois 61443 United States
      • Illinois CancerCare-Macomb
      • Macomb Illinois 61455 United States
      • Carle Physician Group-Mattoon/Charleston
      • Mattoon Illinois 61938 United States
      • Loyola University Medical Center
      • Maywood Illinois 60153 United States
      • Good Samaritan Regional Health Center
      • Mount Vernon Illinois 62864 United States
      • Edward Hospital/Cancer Center
      • Naperville Illinois 60540 United States
      • Illinois CancerCare-Ottawa Clinic
      • Ottawa Illinois 61350 United States
      • Illinois CancerCare-Pekin
      • Pekin Illinois 61554 United States
      • Illinois CancerCare-Peoria
      • Peoria Illinois 61615 United States
      • Methodist Medical Center of Illinois
      • Peoria Illinois 61636 United States
      • OSF Saint Francis Medical Center
      • Peoria Illinois 61637 United States
      • Illinois CancerCare-Peru
      • Peru Illinois 61354 United States
      • Edward Hospital/Cancer Center?Plainfield
      • Plainfield Illinois 60585 United States
      • Illinois CancerCare-Princeton
      • Princeton Illinois 61356 United States
      • Southern Illinois University School of Medicine
      • Springfield Illinois 62702 United States
      • Springfield Clinic
      • Springfield Illinois 62702 United States
      • Memorial Medical Center
      • Springfield Illinois 62781 United States
      • Carle Cancer Center
      • Urbana Illinois 61801 United States
      • The Carle Foundation Hospital
      • Urbana Illinois 61801 United States
      • Rush-Copley Healthcare Center
      • Yorkville Illinois 60560 United States
      • Indiana University/Melvin and Bren Simon Cancer Center
      • Indianapolis Indiana 46202 United States
      • Community Cancer Center East
      • Indianapolis Indiana 46219 United States
      • Community Cancer Center South
      • Indianapolis Indiana 46227 United States
      • Community Cancer Center North
      • Indianapolis Indiana 46256 United States
      • Community Howard Regional Health
      • Kokomo Indiana 46904 United States
      • Reid Health
      • Richmond Indiana 47374 United States
      • Cancer Center of Kansas - Chanute
      • Chanute Kansas 66720 United States
      • Cancer Center of Kansas - Dodge City
      • Dodge City Kansas 67801 United States
      • Cancer Center of Kansas - El Dorado
      • El Dorado Kansas 67042 United States
      • Cancer Center of Kansas - Fort Scott
      • Fort Scott Kansas 66701 United States
      • Hays Medical Center
      • Hays Kansas 67601 United States
      • Cancer Center of Kansas-Independence
      • Independence Kansas 67301 United States
      • University of Kansas Cancer Center
      • Kansas City Kansas 66160 United States
      • Cancer Center of Kansas-Kingman
      • Kingman Kansas 67068 United States
      • Lawrence Memorial Hospital
      • Lawrence Kansas 66044 United States
      • Cancer Center of Kansas-Liberal
      • Liberal Kansas 67905 United States
      • Cancer Center of Kansas-Manhattan
      • Manhattan Kansas 66502 United States
      • Cancer Center of Kansas - McPherson
      • McPherson Kansas 67460 United States
      • Cancer Center of Kansas - Newton
      • Newton Kansas 67114 United States
      • Olathe Medical Center
      • Olathe Kansas 66061 United States
      • Cancer Center of Kansas - Parsons
      • Parsons Kansas 67357 United States
      • Via Christi Hospital-Pittsburg
      • Pittsburg Kansas 66762 United States
      • Cancer Center of Kansas - Pratt
      • Pratt Kansas 67124 United States
      • Cancer Center of Kansas - Salina
      • Salina Kansas 67401 United States
      • Salina Regional Health Center
      • Salina Kansas 67401 United States
      • Saint Francis Hospital and Medical Center - Topeka
      • Topeka Kansas 66606 United States
      • Cancer Center of Kansas - Wellington
      • Wellington Kansas 67152 United States
      • University of Kansas Hospital-Westwood Cancer Center
      • Westwood Kansas 66205 United States
      • Cancer Center of Kansas-Wichita Medical Arts Tower
      • Wichita Kansas 67208 United States
      • Cancer Center of Kansas - Wichita
      • Wichita Kansas 67214 United States
      • Via Christi Regional Medical Center
      • Wichita Kansas 67214 United States
      • Cancer Center of Kansas - Winfield
      • Winfield Kansas 67156 United States
      • University of Kentucky/Markey Cancer Center
      • Lexington Kentucky 40536 United States
      • East Jefferson General Hospital
      • Metairie Louisiana 70006 United States
      • LSU Healthcare Network / Metairie Multi-Specialty Clinic
      • Metairie Louisiana 70006 United States
      • Louisiana State University Health Science Center
      • New Orleans Louisiana 70112 United States
      • Louisiana State University Health Sciences Center Shreveport
      • Shreveport Louisiana 71103 United States
      • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Baltimore Maryland 21287 United States
      • Boston Medical Center
      • Boston Massachusetts 02118 United States
      • Lowell General Hospital
      • Lowell Massachusetts 01854 United States
      • Saint Joseph Mercy Hospital
      • Ann Arbor Michigan 48106 United States
      • IHA Hematology Oncology Consultants-Brighton
      • Brighton Michigan 48114 United States
      • Saint Joseph Mercy Brighton
      • Brighton Michigan 48114 United States
      • IHA Hematology Oncology Consultants-Canton
      • Canton Michigan 48188 United States
      • Saint Joseph Mercy Canton
      • Canton Michigan 48188 United States
      • Caro Cancer Center
      • Caro Michigan 48723 United States
      • IHA Hematology Oncology Consultants-Chelsea
      • Chelsea Michigan 48118 United States
      • Saint Joseph Mercy Chelsea
      • Chelsea Michigan 48118 United States
      • Hematology Oncology Consultants-Clarkston
      • Clarkston Michigan 48346 United States
      • Newland Medical Associates-Clarkston
      • Clarkston Michigan 48346 United States
      • Michigan State University Clinical Center
      • East Lansing Michigan 48824-7016 United States
      • Genesee Cancer and Blood Disease Treatment Center
      • Flint Michigan 48503 United States
      • Genesee Hematology Oncology PC
      • Flint Michigan 48503 United States
      • Genesys Hurley Cancer Institute
      • Flint Michigan 48503 United States
      • Sparrow Hospital
      • Lansing Michigan 48912 United States
      • Saint Mary's Oncology/Hematology Associates of Marlette
      • Marlette Michigan 48453 United States
      • Newland Medical Associates-Pontiac
      • Pontiac Michigan 48341 United States
      • Saint Joseph Mercy Oakland
      • Pontiac Michigan 48341 United States
      • Ascension Saint Mary's Hospital
      • Saginaw Michigan 48601 United States
      • Oncology Hematology Associates of Saginaw Valley PC
      • Saginaw Michigan 48604 United States
      • Saint Mary's Oncology/Hematology Associates of West Branch
      • West Branch Michigan 48661 United States
      • Huron Gastroenterology PC
      • Ypsilanti Michigan 48106 United States
      • IHA Hematology Oncology Consultants-Ann Arbor
      • Ypsilanti Michigan 48197 United States
      • Fairview Ridges Hospital
      • Burnsville Minnesota 55337 United States
      • Essentia Health - Deer River Clinic
      • Deer River Minnesota 56636 United States
      • Essentia Health Cancer Center
      • Duluth Minnesota 55805 United States
      • Essentia Health Saint Mary's Medical Center
      • Duluth Minnesota 55805 United States
      • Miller-Dwan Hospital
      • Duluth Minnesota 55805 United States
      • Saint Luke's Hospital of Duluth
      • Duluth Minnesota 55805 United States
      • Fairview-Southdale Hospital
      • Edina Minnesota 55435 United States
      • Essentia Health Hibbing Clinic
      • Hibbing Minnesota 55746 United States
      • Coborn Cancer Center at Saint Cloud Hospital
      • Saint Cloud Minnesota 56303 United States
      • Saint Cloud Hospital
      • Saint Cloud Minnesota 56303 United States
      • Park Nicollet Clinic - Saint Louis Park
      • Saint Louis Park Minnesota 55416 United States
      • Essentia Health Virginia Clinic
      • Virginia Minnesota 55792 United States
      • Fairview Lakes Medical Center
      • Wyoming Minnesota 55092 United States
      • Parkland Health Center-Bonne Terre
      • Bonne Terre Missouri 63628 United States
      • Saint Francis Medical Center
      • Cape Girardeau Missouri 63703 United States
      • Southeast Cancer Center
      • Cape Girardeau Missouri 63703 United States
      • University of Missouri - Ellis Fischel
      • Columbia Missouri 65212 United States
      • Kansas City Veterans Affairs Medical Center
      • Kansas City Missouri 64128 United States
      • Missouri Baptist Medical Center
      • Saint Louis Missouri 63131 United States
      • Sainte Genevieve County Memorial Hospital
      • Sainte Genevieve Missouri 63670 United States
      • Missouri Baptist Sullivan Hospital
      • Sullivan Missouri 63080 United States
      • Missouri Baptist Outpatient Center-Sunset Hills
      • Sunset Hills Missouri 63127 United States
      • Benefis Healthcare- Sletten Cancer Institute
      • Great Falls Montana 59405 United States
      • Saint Patrick Hospital - Community Hospital
      • Missoula Montana 59802 United States
      • Nebraska Medicine-Village Pointe
      • Omaha Nebraska 68118 United States
      • University of Nebraska Medical Center
      • Omaha Nebraska 68198 United States
      • Cancer and Blood Specialists-Henderson
      • Henderson Nevada 89052 United States
      • Ann M Wierman MD LTD
      • Las Vegas Nevada 89128 United States
      • Comprehensive Cancer Centers of Nevada - Northwest
      • Las Vegas Nevada 89128 United States
      • OptumCare Cancer Care at MountainView
      • Las Vegas Nevada 89128 United States
      • Comprehensive Cancer Centers of Nevada - Town Center
      • Las Vegas Nevada 89144 United States
      • Comprehensive Cancer Centers of Nevada
      • Las Vegas Nevada 89148 United States
      • Comprehensive Cancer Centers of Nevada - Central Valley
      • Las Vegas Nevada 89169 United States
      • Renown Regional Medical Center
      • Reno Nevada 89502 United States
      • Robert Wood Johnson University Hospital Somerset
      • Somerville New Jersey 08876 United States
      • Roswell Park Cancer Institute
      • Buffalo New York 14263 United States
      • Mount Sinai West
      • New York New York 10019 United States
      • NYP/Weill Cornell Medical Center
      • New York New York 10065 United States
      • University of Rochester
      • Rochester New York 14642 United States
      • State University of New York Upstate Medical University
      • Syracuse New York 13210 United States
      • Southeastern Medical Oncology Center-Clinton
      • Clinton North Carolina 28328 United States
      • Southeastern Medical Oncology Center-Goldsboro
      • Goldsboro North Carolina 27534 United States
      • Wayne Memorial Hospital
      • Goldsboro North Carolina 27534 United States
      • Southeastern Medical Oncology Center-Jacksonville
      • Jacksonville North Carolina 28546 United States
      • Veterans Administration Medical Center
      • Salisbury North Carolina 28144 United States
      • Wake Forest University Health Sciences
      • Winston-Salem North Carolina 27157 United States
      • Sanford Bismarck Medical Center
      • Bismarck North Dakota 58501 United States
      • Sanford Broadway Medical Center
      • Fargo North Dakota 58122 United States
      • Sanford Roger Maris Cancer Center
      • Fargo North Dakota 58122 United States
      • Dayton Physician LLC-Miami Valley Hospital North
      • Dayton Ohio 45415 United States
      • Miami Valley Hospital North
      • Dayton Ohio 45415 United States
      • Kettering Medical Center
      • Kettering Ohio 45429 United States
      • Saint Rita's Medical Center
      • Lima Ohio 45801 United States
      • University of Oklahoma Health Sciences Center
      • Oklahoma City Oklahoma 73104 United States
      • Mercy Hospital Oklahoma City
      • Oklahoma City Oklahoma 73120 United States
      • Oklahoma Cancer Specialists and Research Institute-Tulsa
      • Tulsa Oklahoma 74146 United States
      • Saint Alphonsus Medical Center-Baker City
      • Baker City Oregon 97814 United States
      • Legacy Mount Hood Medical Center
      • Gresham Oregon 97030 United States
      • Saint Alphonsus Medical Center-Ontario
      • Ontario Oregon 97914 United States
      • Legacy Good Samaritan Hospital and Medical Center
      • Portland Oregon 97210 United States
      • Legacy Meridian Park Hospital
      • Tualatin Oregon 97062 United States
      • Christiana Care Health System-Concord Health Center
      • Chadds Ford Pennsylvania 19317 United States
      • Allegheny General Hospital
      • Pittsburgh Pennsylvania 15212 United States
      • Greenville Health System Cancer Institute-Laurens
      • Clinton South Carolina 29325 United States
      • Greenville Health System Cancer Institute-Easley
      • Easley South Carolina 29640 United States
      • Greenville Health System Cancer Institute-Butternut
      • Greenville South Carolina 29605 United States
      • Greenville Health System Cancer Institute-Faris
      • Greenville South Carolina 29605 United States
      • Greenville Memorial Hospital
      • Greenville South Carolina 29605 United States
      • Greenville Health System Cancer Institute-Eastside
      • Greenville South Carolina 29615 United States
      • Greenville Health System Cancer Institute-Greer
      • Greer South Carolina 29650 United States
      • Greenville Health System Cancer Institute-Seneca
      • Seneca South Carolina 29672 United States
      • Greenville Health System Cancer Institute-Spartanburg
      • Spartanburg South Carolina 29307 United States
      • Sanford Cancer Center Oncology Clinic
      • Sioux Falls South Dakota 57104 United States
      • Sanford USD Medical Center - Sioux Falls
      • Sioux Falls South Dakota 57117-5134 United States
      • University of Texas Medical Branch
      • Galveston Texas 77555-0565 United States
      • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
      • Houston Texas 77030 United States
      • UTMB Cancer Center at Victory Lakes
      • League City Texas 77573 United States
      • Audie L Murphy VA Hospital
      • San Antonio Texas 78229 United States
      • University Hospital
      • San Antonio Texas 78229 United States
      • University of Texas Health Science Center at San Antonio
      • San Antonio Texas 78229 United States
      • Farmington Health Center
      • Farmington Utah 84025 United States
      • Huntsman Cancer Institute/University of Utah
      • Salt Lake City Utah 84112 United States
      • South Jordan Health Center
      • South Jordan Utah 84009 United States
      • Centra Lynchburg Hematology-Oncology Clinic Inc
      • Lynchburg Virginia 24501 United States
      • Virginia Commonwealth University/Massey Cancer Center
      • Richmond Virginia 23298 United States
      • Swedish Medical Center-First Hill
      • Seattle Washington 98122-4307 United States
      • Legacy Salmon Creek Hospital
      • Vancouver Washington 98686 United States
      • West Virginia University Charleston Division
      • Charleston West Virginia 25304 United States
      • Duluth Clinic Ashland
      • Ashland Wisconsin 54806 United States
      • Aurora Cancer Care-Southern Lakes VLCC
      • Burlington Wisconsin 53105 United States
      • Marshfield Clinic-Chippewa Center
      • Chippewa Falls Wisconsin 54729 United States
      • Marshfield Medical Center-EC Cancer Center
      • Eau Claire Wisconsin 54701 United States
      • Aurora Health Center-Fond du Lac
      • Fond Du Lac Wisconsin 54937 United States
      • Aurora Health Care Germantown Health Center
      • Germantown Wisconsin 53022 United States
      • Aurora Cancer Care-Grafton
      • Grafton Wisconsin 53024 United States
      • Aurora BayCare Medical Center
      • Green Bay Wisconsin 54311 United States
      • Aurora Cancer Care-Kenosha South
      • Kenosha Wisconsin 53142 United States
      • Marshfield Clinic - Ladysmith Center
      • Ladysmith Wisconsin 54848 United States
      • University of Wisconsin Hospital and Clinics
      • Madison Wisconsin 53792 United States
      • Aurora Bay Area Medical Group-Marinette
      • Marinette Wisconsin 54143 United States
      • Marshfield Medical Center-Marshfield
      • Marshfield Wisconsin 54449 United States
      • Aurora Cancer Care-Milwaukee
      • Milwaukee Wisconsin 53209 United States
      • Aurora Saint Luke's Medical Center
      • Milwaukee Wisconsin 53215 United States
      • Aurora Sinai Medical Center
      • Milwaukee Wisconsin 53233 United States
      • Marshfield Clinic-Minocqua Center
      • Minocqua Wisconsin 54548 United States
      • Vince Lombardi Cancer Clinic - Oshkosh
      • Oshkosh Wisconsin 54904 United States
      • Aurora Cancer Care-Racine
      • Racine Wisconsin 53406 United States
      • Marshfield Medical Center-Rice Lake
      • Rice Lake Wisconsin 54868 United States
      • Vince Lombardi Cancer Clinic-Sheboygan
      • Sheboygan Wisconsin 53081 United States
      • Marshfield Clinic Stevens Point Center
      • Stevens Point Wisconsin 54482 United States
      • Aurora Medical Center in Summit
      • Summit Wisconsin 53066 United States
      • Vince Lombardi Cancer Clinic-Two Rivers
      • Two Rivers Wisconsin 54241 United States
      • Marshfield Clinic-Wausau Center
      • Wausau Wisconsin 54401 United States
      • Aurora Cancer Care-Milwaukee West
      • Wauwatosa Wisconsin 53226 United States
      • Aurora West Allis Medical Center
      • West Allis Wisconsin 53227 United States
      • Marshfield Clinic - Weston Center
      • Weston Wisconsin 54476 United States
      • Marshfield Clinic - Wisconsin Rapids Center
      • Wisconsin Rapids Wisconsin 54494 United States
      • Cross Cancer Institute
      • Edmonton Alberta T6G 1Z2 Canada
      • The Research Institute of the McGill University Health Centre (MUHC)
      • Montreal Quebec H3H 2R9 Canada
      • Allan Blair Cancer Centre
      • Regina Saskatchewan S4T 7T1 Canada

      View trial on ClinicalTrials.gov


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      Published October 9, 2017
    23. Phase II Trial of Neoadjuvant Nivolumab With Cisplatin and Gemcitabine in Muscle-Invasive Bladder Cancer (MIBC) Patients Undergoing Radical Cystectomy

      {{header-clinical-trials-navigation}}

      BLASST-1 (Bladder Cancer Signal Seeking Trial): Phase II Trial of Neoadjuvant Nivolumab With Cisplatin and Gemcitabine in Muscle-Invasive Bladder Cancer (MIBC) Patients Undergoing Radical Cystectomy


      Condition: Muscle Invasive Bladder Cancer

      Intervention:

      • Drug: Nivolumab
      • Drug: Cisplatin
      • Drug: Gemcitabine

      Purpose: This is a multi-center Phase II study to determine the safety and efficacy of nivolumab when given in combination with cisplatin and gemcitabine as neoadjuvant treatment in patients with muscle-invasive bladder cancer (MIBC) prior to standard of care radical cystectomy. Patients will receive neoadjuvant treatment with nivolumab in combination with gemcitabine-cisplatin (GC) every 3 weeks for 4 treatment cycles over 12 weeks followed by standard of care radical cystectomy.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT03294304

      Sponsor: Masonic Cancer Center, University of Minnesota

      Primary Outcome Measures:

      • Measure: Pathologic Response Rate (PaR) at time of radical cystectomy. PaR is defined as absence of residual MIBC at cystectomy in the surgical specimen (pathologic down-staging to ≤pT1pN0, which includes pT0, pT1,pTa and pTis)
      • Time Frame: Surgery Day 1
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Safety of Nivolumab with Gemcitabine/Cisplatin (cycle 1)
      • Time Frame: Day 1
      • Safety Issue:
      • Measure: Safety of Nivolumab with Gemcitabine/Cisplatin (cycle 1)
      • Time Frame: Day 8
      • Safety Issue:
      • Measure: Safety of Nivolumab with Gemcitabine/Cisplatin (cycle 2)
      • Time Frame: Day 1
      • Safety Issue:
      • Measure: Safety of Nivolumab with Gemcitabine/Cisplatin (cycle 2)
      • Time Frame: Day 8
      • Safety Issue:
      • Measure: Safety of Nivolumab with Gemcitabine/Cisplatin (cycle 3)
      • Time Frame: Day 1
      • Safety Issue:
      • Measure: Safety of Nivolumab with Gemcitabine/Cisplatin (cycle 3)
      • Time Frame: Day 8
      • Safety Issue:
      • Measure: Safety of Nivolumab with Gemcitabine/Cisplatin (cycle 4)
      • Time Frame: Day 1
      • Safety Issue:
      • Measure: Safety of Nivolumab with Gemcitabine/Cisplatin (cycle 4)
      • Time Frame: Day 8
      • Safety Issue:
      • Measure: Safety of Nivolumab with Gemcitabine/Cisplatin
      • Time Frame: 30 Days +/- 7 Days after last chemotherapy
      • Safety Issue:
      • Measure: Safety of Nivolumab with Gemcitabine/Cisplatin
      • Time Frame: 4 weeks post radical cystectomy
      • Safety Issue:
      • Measure: Progression Free Survival (PFS)
      • Time Frame: Every 3 Months for 2 Years
      • Safety Issue:

      Estimated Enrollment: 43

      Study Start Date: January 29, 2018

      Phase: Phase 2

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • Diagnosis of MIBC (predominantly urothelial carcinoma) with clinical stage T2-T4a and N<1 disease (solitary lymph node measuring < 2 cm) and M0 and deemed eligible for radical cystectomy.
      • Age ≥ 18 years
      • ECOG Performance Status of 0 or 1.
      • Required initial laboratory values within 14 days of study enrollment:
      • Absolute Neutrophil Count ≥ 1500 cells/mm^3
      • Platelets ≥ 100,000 cells/mm^3
      • Hemoglobin ≥ 9.0 g/dL
      • Bilirubin ≤ 1.5 times the upper limit of normal (ULN) for the institution (For patients with known Gilbert's disease: bilirubin ≤ 3 x ULN)
      • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN for the institution
      • Creatinine clearance ≥ 50 ml/min by Cockcroft-Gault formula or 24 hour urinary clearance (CrCl = [140-age (years)] x actual weight (kg) / [72 x serum Cr (mg/dL)] (if patient is female multiply the above by 0.85) or 24 hour urinary creatinine clearance.
      • Alkaline phosphatase ≤ 2.5 x ULN for the institution
      • INR and aPTT ≤ 1.5 x ULN if not on therapeutic anticoagulation. Patients receiving therapeutic anticoagulation will be allowed if maintained on a stable dose.
      • Females of childbearing potential and males who are not surgically sterile and with partners of childbearing potential must agree to use effective contraception during study treatment for 5 months for females and 7 months for males after the last dose of nivolumab.
      • Ability to provide a signed and dated consent or have a legally authorized representative to provide written and signed consent prior to the initiation of any research related procedures.
      • Patient must agree to submission of archived tumor (20-25 formalin-fixed paraffin embedded (FFPE) slides of 5-10 microns in thickness) from TURBT and radical cystectomy tissues. If archived samples are not available fresh tissue will be used.
      • Ability to provide written consent prior to the initiation of any research related procedures.

      Exclusion Criteria:

      • Presence of N2-3 or M1 disease.
      • Ineligible to receive cisplatin by meeting one or more of the following criteria;
      • Creatinine clearance of < 50 mL/min
      • Hearing loss of 25 dB at two contiguous frequencies with testing required if a patient has hearing loss
      • At the investigator's discretion, and after discussion with the patient, this exclusion may be waived if the potential benefit of cisplatin therapy is felt to outweigh the risk of further hearing loss.
      • CTCAE v4 Grade 2 or higher peripheral neuropathy,
      • New York Heart Association Class III or IV heart failure
      • ECOG performance status 2 or higher.
      • Prior systemic therapy (intravenous) is not permitted. Prior intravesical therapies including intravesical gemcitabine is permitted for non-muscle invasive disease (i.e. T1 or lower).
      • Prior treatment with cisplatin for bladder cancer.
      • Prior treatment with anti-PD-1, CTLA-4, or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
      • Prior therapeutic radiation to the bladder.
      • Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study.
      • Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (>New York Heart Association Class 2), stroke, serious cardiac arrhythmia.
      • Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness.
      • Pregnancy, lactation, or breast-feeding. Women of childbearing potential must have a negative urine pregnancy test at screening.
      • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, systemic vasculitis, or glomerulonephritis.
      • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan, history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
      • Active hepatitis B virus (HBV, chronic or acute, defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C antibody. Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBc Ab] and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1 and confirmed to be negative. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
      • Active tuberculosis or BCG infection
      • Active infection requiring systemic antibiotics for more than 7 days within 3 days prior to Cycle 1, Day 1. Prophylactic short-term antibiotics will be allowed.
      • Administration of intravesical bacillus Calmette-Guerin (BCG) within 4 weeks before Cycle 1, Day 1
      • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study.
      • Persisting toxicity from prior therapy (NCI CTCAE v4.03 Grade >1); however alopecia or other Grade <2 AEs not constituting a safety risk, based on Investigator's judgement, are acceptable.
      • History of or active bone marrow disorders expected to interfere with study therapy (e.g. acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma).
      • Prior allogeneic stem cell or solid organ transplant.
      • Known primary central nervous system (CNS) malignancy.
      • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted but patients with psoriasis require a baseline ophthalmologic exam to rule out ocular manifestations. Rash must cover less than 10% of body surface area (BSA) and must be well controlled at baseline and only requiring topical steroids.
      • Any other chronic medical condition or psychiatric condition, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
      • Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative therapy. Patients on androgen deprivation therapy as part of adjuvant therapy after radiation for prostate cancer or patients on adjuvant hormonal therapies for breast cancer will be allowed if they are being considered for curative intent for bladder cancer.
      • Treatment with systemic immunostimulatory agents (including but not limited to interferon [IFN]-a or interleukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1
      • Concomitant use of systemic corticosteroids at physiologic doses or <10 mg/day of prednisone or equivalent.
      • Concomitant use of another investigational agent and/or treatment with an investigational agent within 4 weeks prior to Cycle 1, Day 1 (or within five halflives of the investigational product, whichever is longer).
      • Use of bisphosphonate therapy for osteoporosis will be allowed if started prior to study enrollment.

      Locations:

      • Dana-Farber Cancer Institute
      • Boston Massachusetts 02215 United States
      • Masonic Cancer Center - University of Minnesota
      • Minneapolis Minnesota 55455 United States
      • Huntsman Cancer Institute - University of Utah Health
      • Salt Lake City Utah 84112 United States

      View trial on ClinicalTrials.gov


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      Published September 28, 2017
    24. Phase III Randomized Adjuvant Study of MK-3475 (Pembrolizumab) in Muscle Invasive and Locally Advanced Urothelial Carcinoma (AMBASSADOR) Versus Observation

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      Phase III Randomized Adjuvant Study of MK-3475 (Pembrolizumab) in Muscle Invasive and Locally Advanced Urothelial Carcinoma (AMBASSADOR) Versus Observation


      Condition: Stage II Bladder Urothelial Carcinoma AJCC v6 and v7, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7

      Intervention:

      • Other: Clinical Observation
      • Other: Laboratory Biomarker Analysis
      • Biological: Pembrolizumab
      • Other: Pharmacological Study
      • Other: Quality-of-Life Assessment
      • Other: Questionnaire Administration

      Purpose: This randomized phase III trial studies how well pembrolizumab works in treating patients with bladder cancer that has spread from where it started to nearby tissue or lymph nodes. Monoclonal antibodies recognizing and blocking checkpoint molecules can enhance the patient's immune response and therefore help fight cancer. Pembrolizumab is one of the monoclonal antibodies that block the PD-1 axis and can interfere with the ability of tumor cells to grow.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT03244384

      Sponsor: National Cancer Institute (NCI)

      Primary Outcome Measures:

      • Measure: Overall survival
      • Time Frame: From randomization to the date of death from any cause, assessed up to 5 years
      • Safety Issue:
      • Measure: Disease-free survival
      • Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Overall survival in PD-L1 positive and negative patients
      • Time Frame: From randomization to the date of death from any cause, assessed up to 5 years
      • Safety Issue:
      • Measure: Disease-free survival in PD-L1 positive and negative patients
      • Time Frame: From randomization to the first metastatic recurrence (presence of any recurrent disease), or death, whichever occurs first, assessed up to 5 years
      • Safety Issue:

      Estimated Enrollment: 739

      Study Start Date: September 21, 2017

      Phase: Phase 3

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • PRE-REGISTRATION ELIGIBILITY CRITERIA
      • Histologically confirmed muscle-invasive urothelial carcinoma of the bladder or upper tract; variant histology allowed as long as urothelial carcinoma is predominant (> 50%); pure small-cell carcinoma is excluded
      • Paraffin tissue samples obtained by transurethral resection of muscle-invasive bladder tumor, upper tract resection, cystectomy/nephrectomy/ureterectomy, or nephroureterectomy must be available; this specimen submission is mandatory prior to registration as results will be used for stratification
      • Patient must fit into one of the following three categories:
      • Patients who received neoadjuvant chemotherapy and pathologic stage at surgical resection is >= pT2 and/or N+ OR
      • Patients who are not cisplatin-eligible (according to >= 1 of the following criteria: Eastern Cooperative Oncology Group [ECOG] performance status of 2, creatinine clearance < 60 mL/min, grade >= 2 hearing loss, grade >= 2 neuropathy, or New York Heart Association class III heart failure and pathologic stage at surgical resection is >= pT3 or pN+) OR
      • Patients that decline adjuvant cisplatin-based or other systemic chemotherapy based on an informed discussion with the physician and pathologic stage at surgical resection is >= pT3 or pN+
      • Patient must have had radical surgical resection of their bladder cancer >= 4 weeks but =< 16 weeks prior to pre-registration
      • No invasive cancer at the surgical margins
      • No evidence of residual cancer or metastasis after surgery
      • No metastatic disease on cross-sectional imaging (according to Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1 criteria)
      • No active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease; human immunodeficiency virus (HIV) (+) patients are eligible as long as they have: cd4 > 200, undetectable viral load and on highly active antiretroviral therapy (HAART) therapy
      • No current pneumonitis or prior history of non-infectious pneumonitis that required steroids within the previous 5 years
      • Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible
      • Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
      • No known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
      • No postoperative/adjuvant systemic therapy
      • No prior treatment with any therapy on the PD-1/PD-L1 axis
      • No treatment with any other type of investigational agent =< 4 weeks before pre-registration
      • No major surgery =< 4 weeks before pre-registration
      • No radiation therapy =< 4 weeks before pre-registration
      • No neoadjuvant chemotherapy =< 4 weeks before pre-registration
      • Not pregnant and not nursing
      • ECOG performance status =< 2
      • Absolute neutrophil count (ANC) >= 1,200/mm^3
      • Leukocytes >= 3,000/ mm^3
      • Platelet count >= 75,000/mm^3
      • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
      • Creatinine =< 2.0 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance >= 30 mL/min
      • Total bilirubin =< 1.5 x upper limit of normal (ULN)
      • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x upper limit of normal (ULN)
      • Serum albumin >= 2.8 g/dL
      • For women of childbearing potential only: a negative urine or serum pregnancy test done =< 7 days prior to pre-registration is required
      • REGISTRATION ELIGIBILITY CRITERIA
      • Results of central PD-L1 testing available; Q2 Solutions will forward the PD-L1 results to the statistical center and the statistical center will notify the site that the result is available; the notification from the Alliance registration/randomization office will serve as a confirmation of this

      Eligibility Criteria:

      • Histologically confirmed muscle-invasive urothelial carcinoma of the bladder or upper tract; variant histology allowed as long as urothelial carcinoma is predominant (> 50%); pure small-cell carcinoma is excluded
      • Paraffin tissue samples obtained by transurethral resection of muscle-invasive bladder tumor, upper tract resection, cystectomy/nephrectomy/ureterectomy, or nephroureterectomy must be available; this specimen submission is mandatory prior to registration as results will be used for stratification
      • Patient must fit into one of the following three categories:
      • Patients who received neoadjuvant chemotherapy and pathologic stage at surgical resection is >= pT2 and/or N+ OR
      • Patients who are not cisplatin-eligible (according to >= 1 of the following criteria: Eastern Cooperative Oncology Group [ECOG] performance status of 2, creatinine clearance < 60 mL/min, grade >= 2 hearing loss, grade >= 2 neuropathy, or New York Heart Association class III heart failure and pathologic stage at surgical resection is >= pT3 or pN+) OR
      • Patients that decline adjuvant cisplatin-based or other systemic chemotherapy based on an informed discussion with the physician and pathologic stage at surgical resection is >= pT3 or pN+
      • Patient must have had radical surgical resection of their bladder cancer >= 4 weeks but =< 16 weeks prior to pre-registration
      • No invasive cancer at the surgical margins
      • No evidence of residual cancer or metastasis after surgery
      • No metastatic disease on cross-sectional imaging (according to Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1 criteria)
      • No active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease; human immunodeficiency virus (HIV) (+) patients are eligible as long as they have: cd4 > 200, undetectable viral load and on highly active antiretroviral therapy (HAART) therapy
      • No current pneumonitis or prior history of non-infectious pneumonitis that required steroids within the previous 5 years
      • Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible
      • Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
      • No known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
      • No postoperative/adjuvant systemic therapy
      • No prior treatment with any therapy on the PD-1/PD-L1 axis
      • No treatment with any other type of investigational agent =< 4 weeks before pre-registration
      • No major surgery =< 4 weeks before pre-registration
      • No radiation therapy =< 4 weeks before pre-registration
      • No neoadjuvant chemotherapy =< 4 weeks before pre-registration
      • Not pregnant and not nursing
      • ECOG performance status =< 2
      • Absolute neutrophil count (ANC) >= 1,200/mm^3
      • Leukocytes >= 3,000/ mm^3
      • Platelet count >= 75,000/mm^3
      • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
      • Creatinine =< 2.0 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance >= 30 mL/min
      • Total bilirubin =< 1.5 x upper limit of normal (ULN)
      • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x upper limit of normal (ULN)
      • Serum albumin >= 2.8 g/dL
      • For women of childbearing potential only: a negative urine or serum pregnancy test done =< 7 days prior to pre-registration is required
      • REGISTRATION ELIGIBILITY CRITERIA
      • Results of central PD-L1 testing available; Q2 Solutions will forward the PD-L1 results to the statistical center and the statistical center will notify the site that the result is available; the notification from the Alliance registration/randomization office will serve as a confirmation of this eligibility criteria; after sites receive the confirmation e-mail from Alliance they can register the patient

      Locations:

      • Anchorage Associates in Radiation Medicine
      • Anchorage Alaska 98508 United States
      • Anchorage Radiation Therapy Center
      • Anchorage Alaska 99504 United States
      • Alaska Breast Care and Surgery LLC
      • Anchorage Alaska 99508 United States
      • Alaska Oncology and Hematology LLC
      • Anchorage Alaska 99508 United States
      • Alaska Women's Cancer Care
      • Anchorage Alaska 99508 United States
      • Anchorage Oncology Centre
      • Anchorage Alaska 99508 United States
      • Katmai Oncology Group
      • Anchorage Alaska 99508 United States
      • Providence Alaska Medical Center
      • Anchorage Alaska 99508 United States
      • Fairbanks Memorial Hospital
      • Fairbanks Alaska 99701 United States
      • CTCA at Western Regional Medical Center
      • Goodyear Arizona 85338 United States
      • Kingman Regional Medical Center
      • Kingman Arizona 86401 United States
      • Mayo Clinic Hospital
      • Phoenix Arizona 85054 United States
      • Mayo Clinic in Arizona
      • Scottsdale Arizona 85259 United States
      • Mercy Hospital Fort Smith
      • Fort Smith Arkansas 72903 United States
      • John L McClellan Memorial Veterans Hospital
      • Little Rock Arkansas 72205 United States
      • Kaiser Permanente-Anaheim
      • Anaheim California 92806 United States
      • PCR Oncology
      • Arroyo Grande California 93420 United States
      • AIS Cancer Center at San Joaquin Community Hospital
      • Bakersfield California 93301 United States
      • Kaiser Permanente-Baldwin Park
      • Baldwin Park California 91706 United States
      • Kaiser Permanente-Bellflower
      • Bellflower California 90706 United States
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
      • Burbank California 91505 United States
      • Epic Care-Dublin
      • Dublin California 94568 United States
      • Bay Area Breast Surgeons Inc
      • Emeryville California 94608 United States
      • Epic Care Partners in Cancer Care
      • Emeryville California 94608 United States
      • Kaiser Permanente-Fontana
      • Fontana California 92335 United States
      • Kaiser Permanente - Harbor City
      • Harbor City California 90710 United States
      • Kaiser Permanente-Irvine
      • Irvine California 92618 United States
      • UC San Diego Moores Cancer Center
      • La Jolla California 92093 United States
      • Kaiser Permanente Los Angeles Medical Center
      • Los Angeles California 90027 United States
      • Los Angeles County-USC Medical Center
      • Los Angeles California 90033 United States
      • USC / Norris Comprehensive Cancer Center
      • Los Angeles California 90033 United States
      • Kaiser Permanente-Cadillac
      • Los Angeles California 90034 United States
      • Contra Costa Regional Medical Center
      • Martinez California 94553-3156 United States
      • Fremont - Rideout Cancer Center
      • Marysville California 95901 United States
      • Community Hospital of Monterey Peninsula
      • Monterey California 93940 United States
      • Pacific Cancer Care-Monterey
      • Monterey California 93940 United States
      • USC Norris Oncology/Hematology-Newport Beach
      • Newport Beach California 92663 United States
      • Alta Bates Summit Medical Center - Summit Campus
      • Oakland California 94609 United States
      • Bay Area Tumor Institute
      • Oakland California 94609 United States
      • Kaiser Permanente-Ontario
      • Ontario California 91761 United States
      • Stanford Cancer Institute Palo Alto
      • Palo Alto California 94304 United States
      • Kaiser Permanente - Panorama City
      • Panorama City California 91402 United States
      • Keck Medical Center of USC Pasadena
      • Pasadena California 91105 United States
      • Kaiser Permanente-Riverside
      • Riverside California 92505 United States
      • University of California Davis Comprehensive Cancer Center
      • Sacramento California 95817 United States
      • Kaiser Permanente-San Diego Mission
      • San Diego California 92108 United States
      • Kaiser Permanente-San Diego Zion
      • San Diego California 92120 United States
      • Kaiser Permanente-San Marcos
      • San Marcos California 92078 United States
      • Gene Upshaw Memorial Tahoe Forest Cancer Center
      • Truckee California 96161 United States
      • Epic Care Cyberknife Center
      • Walnut Creek California 94597 United States
      • Kaiser Permanente-Woodland Hills
      • Woodland Hills California 91367 United States
      • Rocky Mountain Cancer Centers-Aurora
      • Aurora Colorado 80012 United States
      • The Medical Center of Aurora
      • Aurora Colorado 80012 United States
      • University of Colorado Hospital
      • Aurora Colorado 80045 United States
      • Boulder Community Hospital
      • Boulder Colorado 80301 United States
      • Rocky Mountain Cancer Centers-Boulder
      • Boulder Colorado 80304 United States
      • UCHealth Memorial Hospital Central
      • Colorado Springs Colorado 80909 United States
      • Memorial Hospital North
      • Colorado Springs Colorado 80920 United States
      • Cancer Center of Colorado at Sloan's Lake
      • Denver Colorado 80204 United States
      • Kaiser Permanente-Franklin
      • Denver Colorado 80205 United States
      • National Jewish Health-Main Campus
      • Denver Colorado 80206 United States
      • The Women's Imaging Center
      • Denver Colorado 80209 United States
      • Colorado Blood Cancer Institute
      • Denver Colorado 80218 United States
      • Presbyterian - Saint Lukes Medical Center - Health One
      • Denver Colorado 80218 United States
      • Rocky Mountain Cancer Centers-Midtown
      • Denver Colorado 80218 United States
      • SCL Health Saint Joseph Hospital
      • Denver Colorado 80218 United States
      • Rocky Mountain Cancer Centers-Rose
      • Denver Colorado 80220 United States
      • Rose Medical Center
      • Denver Colorado 80220 United States
      • Western Surgical Care
      • Denver Colorado 80220 United States
      • Mountain Blue Cancer Care Center - Swedish
      • Englewood Colorado 80113 United States
      • Swedish Medical Center
      • Englewood Colorado 80113 United States
      • Poudre Valley Hospital
      • Fort Collins Colorado 80524 United States
      • National Jewish Health-Western Hematology Oncology
      • Golden Colorado 80401 United States
      • Saint Mary's Hospital and Regional Medical Center
      • Grand Junction Colorado 81501 United States
      • Grand Valley Oncology
      • Grand Junction Colorado 81505 United States
      • North Colorado Medical Center
      • Greeley Colorado 80631 United States
      • UCHealth Highlands Ranch Hospital
      • Highlands Ranch Colorado 80129 United States
      • Good Samaritan Medical Center
      • Lafayette Colorado 80026 United States
      • Kaiser Permanente-Rock Creek
      • Lafayette Colorado 80026 United States
      • Rocky Mountain Cancer Centers-Littleton
      • Littleton Colorado 80120 United States
      • Kaiser Permanente-Lone Tree
      • Lone Tree Colorado 80124 United States
      • Rocky Mountain Cancer Centers-Sky Ridge
      • Lone Tree Colorado 80124 United States
      • Sky Ridge Medical Center
      • Lone Tree Colorado 80124 United States
      • McKee Medical Center
      • Loveland Colorado 80539 United States
      • National Jewish Health-Northern Hematology Oncology
      • Thornton Colorado 80260 United States
      • SCL Health Lutheran Medical Center
      • Wheat Ridge Colorado 80033 United States
      • Danbury Hospital
      • Danbury Connecticut 06810 United States
      • Smilow Cancer Hospital-Derby Care Center
      • Derby Connecticut 06418 United States
      • Smilow Cancer Hospital Care Center-Fairfield
      • Fairfield Connecticut 06824 United States
      • Yale-New Haven Shoreline Medical Center
      • Guilford Connecticut 06437 United States
      • Smilow Cancer Hospital Care Center at Saint Francis
      • Hartford Connecticut 06105 United States
      • Middlesex Hospital
      • Middletown Connecticut 06457 United States
      • Smilow Cancer Center/Yale-New Haven Hospital
      • New Haven Connecticut 06510 United States
      • Yale University
      • New Haven Connecticut 06520 United States
      • Smilow Cancer Hospital-Torrington Care Center
      • Torrington Connecticut 06790 United States
      • Smilow Cancer Hospital Care Center-Trumbull
      • Trumbull Connecticut 06611 United States
      • Smilow Cancer Hospital-Waterbury Care Center
      • Waterbury Connecticut 06708 United States
      • Lawrence and Memorial Cancer Center
      • Waterford Connecticut 06385 United States
      • Beebe Medical Center
      • Lewes Delaware 19958 United States
      • Delaware Clinical and Laboratory Physicians PA
      • Newark Delaware 19713 United States
      • Helen F Graham Cancer Center
      • Newark Delaware 19713 United States
      • Medical Oncology Hematology Consultants PA
      • Newark Delaware 19713 United States
      • Christiana Care Health System-Christiana Hospital
      • Newark Delaware 19718 United States
      • Beebe Health Campus
      • Rehoboth Beach Delaware 19971 United States
      • Nanticoke Memorial Hospital
      • Seaford Delaware 19973 United States
      • Christiana Care Health System-Wilmington Hospital
      • Wilmington Delaware 19801 United States
      • MedStar Georgetown University Hospital
      • Washington District of Columbia 20007 United States
      • MedStar Washington Hospital Center
      • Washington District of Columbia 20010 United States
      • George Washington University Medical Center
      • Washington District of Columbia 20037 United States
      • University of Florida Health Science Center - Gainesville
      • Gainesville Florida 32610 United States
      • Emory University Hospital/Winship Cancer Institute
      • Atlanta Georgia 30322 United States
      • Northside Hospital
      • Atlanta Georgia 30342 United States
      • Northside Hospital-Forsyth
      • Cumming Georgia 30041 United States
      • Memorial Health University Medical Center
      • Savannah Georgia 31404 United States
      • Summit Cancer Care-Memorial
      • Savannah Georgia 31404 United States
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
      • Savannah Georgia 31405 United States
      • Low Country Cancer Care Associates PC
      • Savannah Georgia 31405 United States
      • Summit Cancer Care-Candler
      • Savannah Georgia 31405 United States
      • Hawaii Cancer Care - Savio
      • 'Aiea Hawaii 96701 United States
      • Hawaii Oncology Inc-Pali Momi
      • 'Aiea Hawaii 96701 United States
      • Pali Momi Medical Center
      • 'Aiea Hawaii 96701 United States
      • The Cancer Center of Hawaii-Pali Momi
      • 'Aiea Hawaii 96701 United States
      • Hawaii Cancer Care Inc-POB II
      • Honolulu Hawaii 96813 United States
      • Hawaii Oncology Inc-POB I
      • Honolulu Hawaii 96813 United States
      • Island Urology
      • Honolulu Hawaii 96813 United States
      • Queen's Medical Center
      • Honolulu Hawaii 96813 United States
      • Straub Clinic and Hospital
      • Honolulu Hawaii 96813 United States
      • University of Hawaii Cancer Center
      • Honolulu Hawaii 96813 United States
      • Hawaii Cancer Care Inc-Liliha
      • Honolulu Hawaii 96817 United States
      • Hawaii Oncology Inc-Kuakini
      • Honolulu Hawaii 96817 United States
      • Kuakini Medical Center
      • Honolulu Hawaii 96817 United States
      • The Cancer Center of Hawaii-Liliha
      • Honolulu Hawaii 96817 United States
      • Kapiolani Medical Center for Women and Children
      • Honolulu Hawaii 96826 United States
      • Wilcox Memorial Hospital and Kauai Medical Clinic
      • Lihue Hawaii 96766 United States
      • Saint Alphonsus Cancer Care Center-Boise
      • Boise Idaho 83706 United States
      • Saint Luke's Mountain States Tumor Institute
      • Boise Idaho 83712 United States
      • Saint Alphonsus Cancer Care Center-Caldwell
      • Caldwell Idaho 83605 United States
      • Kootenai Medical Center
      • Coeur d'Alene Idaho 83814 United States
      • Walter Knox Memorial Hospital
      • Emmett Idaho 83617 United States
      • Saint Luke's Mountain States Tumor Institute - Fruitland
      • Fruitland Idaho 83619 United States
      • Idaho Urologic Institute-Meridian
      • Meridian Idaho 83642 United States
      • Saint Luke's Mountain States Tumor Institute - Meridian
      • Meridian Idaho 83642 United States
      • Saint Alphonsus Medical Center-Nampa
      • Nampa Idaho 83686 United States
      • Saint Luke's Mountain States Tumor Institute - Nampa
      • Nampa Idaho 83686 United States
      • Kootenai Cancer Center
      • Post Falls Idaho 83854 United States
      • Kootenai Cancer Clinic
      • Sandpoint Idaho 83864 United States
      • Saint Luke's Mountain States Tumor Institute-Twin Falls
      • Twin Falls Idaho 83301 United States
      • Rush - Copley Medical Center
      • Aurora Illinois 60504 United States
      • Illinois CancerCare-Bloomington
      • Bloomington Illinois 61704 United States
      • Loyola Center for Health at Burr Ridge
      • Burr Ridge Illinois 60527 United States
      • Illinois CancerCare-Canton
      • Canton Illinois 61520 United States
      • Memorial Hospital of Carbondale
      • Carbondale Illinois 62902 United States
      • SIH Cancer Institute
      • Carterville Illinois 62918 United States
      • Illinois CancerCare-Carthage
      • Carthage Illinois 62321 United States
      • Centralia Oncology Clinic
      • Centralia Illinois 62801 United States
      • Northwestern University
      • Chicago Illinois 60611 United States
      • University of Illinois
      • Chicago Illinois 60612 United States
      • University of Chicago Comprehensive Cancer Center
      • Chicago Illinois 60637 United States
      • Carle on Vermilion
      • Danville Illinois 61832 United States
      • Cancer Care Specialists of Illinois - Decatur
      • Decatur Illinois 62526 United States
      • Decatur Memorial Hospital
      • Decatur Illinois 62526 United States
      • Northwestern Medicine Cancer Center Kishwaukee
      • DeKalb Illinois 60115 United States
      • Illinois CancerCare-Dixon
      • Dixon Illinois 61021 United States
      • Carle Physician Group-Effingham
      • Effingham Illinois 62401 United States
      • Crossroads Cancer Center
      • Effingham Illinois 62401 United States
      • Illinois CancerCare-Eureka
      • Eureka Illinois 61530 United States
      • Illinois CancerCare-Galesburg
      • Galesburg Illinois 61401 United States
      • Western Illinois Cancer Treatment Center
      • Galesburg Illinois 61401 United States
      • Northwestern Medicine Cancer Center Delnor
      • Geneva Illinois 60134 United States
      • Edward Hines Jr VA Hospital
      • Hines Illinois 60141 United States
      • Presence Saint Mary's Hospital
      • Kankakee Illinois 60901 United States
      • Illinois CancerCare-Kewanee Clinic
      • Kewanee Illinois 61443 United States
      • Northwestern Medicine Lake Forest Hospital
      • Lake Forest Illinois 60045 United States
      • Illinois CancerCare-Macomb
      • Macomb Illinois 61455 United States
      • Carle Physician Group-Mattoon/Charleston
      • Mattoon Illinois 61938 United States
      • Loyola University Medical Center
      • Maywood Illinois 60153 United States
      • Marjorie Weinberg Cancer Center at Loyola-Gottlieb
      • Melrose Park Illinois 60160 United States
      • Good Samaritan Regional Health Center
      • Mount Vernon Illinois 62864 United States
      • UC Comprehensive Cancer Center at Silver Cross
      • New Lenox Illinois 60451 United States
      • Loyola Center for Cancer Care and Research
      • Orland Park Illinois 60462 United States
      • University of Chicago Medicine-Orland Park
      • Orland Park Illinois 60462 United States
      • Illinois CancerCare-Ottawa Clinic
      • Ottawa Illinois 61350 United States
      • Illinois CancerCare-Pekin
      • Pekin Illinois 61554 United States
      • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
      • Pekin Illinois 61554 United States
      • Illinois CancerCare-Peoria
      • Peoria Illinois 61615 United States
      • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
      • Peoria Illinois 61615 United States
      • Methodist Medical Center of Illinois
      • Peoria Illinois 61636 United States
      • OSF Saint Francis Medical Center
      • Peoria Illinois 61637 United States
      • Illinois CancerCare-Peru
      • Peru Illinois 61354 United States
      • Valley Radiation Oncology
      • Peru Illinois 61354 United States
      • Illinois CancerCare-Princeton
      • Princeton Illinois 61356 United States
      • West Suburban Medical Center
      • River Forest Illinois 60305 United States
      • Southern Illinois University School of Medicine
      • Springfield Illinois 62702 United States
      • Springfield Clinic
      • Springfield Illinois 62702 United States
      • Memorial Medical Center
      • Springfield Illinois 62781 United States
      • Cancer Care Specialists of Illinois-Swansea
      • Swansea Illinois 62226 United States
      • Southwest Illinois Health Services LLP
      • Swansea Illinois 62226 United States
      • Carle Cancer Center
      • Urbana Illinois 61801 United States
      • The Carle Foundation Hospital
      • Urbana Illinois 61801 United States
      • Northwestern Medicine Cancer Center Warrenville
      • Warrenville Illinois 60555 United States
      • Rush-Copley Healthcare Center
      • Yorkville Illinois 60560 United States
      • Parkview Hospital Randallia
      • Fort Wayne Indiana 46805 United States
      • Parkview Regional Medical Center
      • Fort Wayne Indiana 46845 United States
      • Community Cancer Center East
      • Indianapolis Indiana 46219 United States
      • Community Cancer Center South
      • Indianapolis Indiana 46227 United States
      • Community Cancer Center North
      • Indianapolis Indiana 46256 United States
      • Community Howard Regional Health
      • Kokomo Indiana 46904 United States
      • Reid Health
      • Richmond Indiana 47374 United States
      • Mary Greeley Medical Center
      • Ames Iowa 50010 United States
      • McFarland Clinic PC - Ames
      • Ames Iowa 50010 United States
      • McFarland Clinic PC-Boone
      • Boone Iowa 50036 United States
      • Iowa Methodist Medical Center
      • Des Moines Iowa 50309 United States
      • Medical Oncology and Hematology Associates-Des Moines
      • Des Moines Iowa 50309 United States
      • Broadlawns Medical Center
      • Des Moines Iowa 50314 United States
      • Iowa Lutheran Hospital
      • Des Moines Iowa 50316 United States
      • McFarland Clinic PC-Trinity Cancer Center
      • Fort Dodge Iowa 50501 United States
      • Trinity Regional Medical Center
      • Fort Dodge Iowa 50501 United States
      • McFarland Clinic PC-Jefferson
      • Jefferson Iowa 50129 United States
      • McFarland Clinic PC-Marshalltown
      • Marshalltown Iowa 50158 United States
      • Methodist West Hospital
      • West Des Moines Iowa 50266-7700 United States
      • Coffeyville Regional Medical Center
      • Coffeyville Kansas 67337 United States
      • University of Kansas Clinical Research Center
      • Fairway Kansas 66205 United States
      • Central Care Cancer Center - Garden City
      • Garden City Kansas 67846 United States
      • Central Care Cancer Center - Great Bend
      • Great Bend Kansas 67530 United States
      • Hays Medical Center
      • Hays Kansas 67601 United States
      • University of Kansas Cancer Center
      • Kansas City Kansas 66160 United States
      • Kansas Institute of Medicine Cancer and Blood Center
      • Lenexa Kansas 66219 United States
      • Minimally Invasive Surgery Hospital
      • Lenexa Kansas 66219 United States
      • Olathe Medical Center
      • Olathe Kansas 66061 United States
      • Menorah Medical Center
      • Overland Park Kansas 66209 United States
      • University of Kansas Cancer Center-Overland Park
      • Overland Park Kansas 66210 United States
      • Saint Luke's South Hospital
      • Overland Park Kansas 66213 United States
      • Via Christi Hospital-Pittsburg
      • Pittsburg Kansas 66762 United States
      • Salina Regional Health Center
      • Salina Kansas 67401 United States
      • Cotton O'Neil Cancer Center / Stormont Vail Health
      • Topeka Kansas 66606 United States
      • Saint Francis Hospital and Medical Center - Topeka
      • Topeka Kansas 66606 United States
      • University of Kansas Hospital-Westwood Cancer Center
      • Westwood Kansas 66205 United States
      • University of Kentucky/Markey Cancer Center
      • Lexington Kentucky 40536 United States
      • Christus Saint Frances Cabrini Hospital
      • Alexandria Louisiana 71301 United States
      • LSU Health Baton Rouge-North Clinic
      • Baton Rouge Louisiana 70805 United States
      • Louisiana Hematology Oncology Associates LLC
      • Baton Rouge Louisiana 70809 United States
      • Mary Bird Perkins Cancer Center
      • Baton Rouge Louisiana 70809 United States
      • Ochsner Health Center-Summa
      • Baton Rouge Louisiana 70809 United States
      • Our Lady of the Lake Physicians Group - Medical Oncology
      • Baton Rouge Louisiana 70809 United States
      • Medical Center of Baton Rouge
      • Baton Rouge Louisiana 70816 United States
      • Ochsner High Grove
      • Baton Rouge Louisiana 70836 United States
      • Northshore Oncology Associates-Covington
      • Covington Louisiana 70433 United States
      • Oncology Center of The South Incorporated
      • Houma Louisiana 70360 United States
      • Terrebonne General Medical Center
      • Houma Louisiana 70360 United States
      • East Jefferson General Hospital
      • Metairie Louisiana 70006 United States
      • LSU Healthcare Network / Metairie Multi-Specialty Clinic
      • Metairie Louisiana 70006 United States
      • Louisiana State University Health Science Center
      • New Orleans Louisiana 70112 United States
      • University Medical Center New Orleans
      • New Orleans Louisiana 70112 United States
      • Ochsner Medical Center Jefferson
      • New Orleans Louisiana 70121 United States
      • CHRISTUS Highland Medical Center
      • Shreveport Louisiana 71105 United States
      • Harold Alfond Center for Cancer Care
      • Augusta Maine 04330 United States
      • Eastern Maine Medical Center
      • Bangor Maine 04401 United States
      • Waldo County General Hospital
      • Belfast Maine 04915 United States
      • MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford
      • Biddeford Maine 04005 United States
      • Lafayette Family Cancer Center-EMMC
      • Brewer Maine 04412 United States
      • Stephens Memorial Hospital
      • Norway Maine 04268 United States
      • Penobscot Bay Medical Center
      • Rockport Maine 04856 United States
      • MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford
      • Sanford Maine 04073 United States
      • Maine Medical Partners - South Portland
      • South Portland Maine 04106 United States
      • MedStar Union Memorial Hospital
      • Baltimore Maryland 21218 United States
      • MedStar Franklin Square Medical Center/Weinberg Cancer Institute
      • Baltimore Maryland 21237 United States
      • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Baltimore Maryland 21287 United States
      • National Institutes of Health Clinical Center
      • Bethesda Maryland 20892 United States
      • Massachusetts General Hospital Cancer Center
      • Boston Massachusetts 02114 United States
      • Boston Medical Center
      • Boston Massachusetts 02118 United States
      • Dana-Farber Cancer Institute
      • Boston Massachusetts 02215 United States
      • Lahey Hospital and Medical Center
      • Burlington Massachusetts 01805 United States
      • Lowell General Hospital
      • Lowell Massachusetts 01854 United States
      • Mercy Medical Center
      • Springfield Massachusetts 01104 United States
      • Hickman Cancer Center
      • Adrian Michigan 49221 United States
      • Saint Joseph Mercy Hospital
      • Ann Arbor Michigan 48106 United States
      • University of Michigan Comprehensive Cancer Center
      • Ann Arbor Michigan 48109 United States
      • Bronson Battle Creek
      • Battle Creek Michigan 49017 United States
      • IHA Hematology Oncology Consultants-Brighton
      • Brighton Michigan 48114 United States
      • Saint Joseph Mercy Brighton
      • Brighton Michigan 48114 United States
      • Henry Ford Cancer Institute-Downriver
      • Brownstown Michigan 48183 United States
      • IHA Hematology Oncology Consultants-Canton
      • Canton Michigan 48188 United States
      • Saint Joseph Mercy Canton
      • Canton Michigan 48188 United States
      • Caro Cancer Center
      • Caro Michigan 48723 United States
      • IHA Hematology Oncology Consultants-Chelsea
      • Chelsea Michigan 48118 United States
      • Saint Joseph Mercy Chelsea
      • Chelsea Michigan 48118 United States
      • Hematology Oncology Consultants-Clarkston
      • Clarkston Michigan 48346 United States
      • Newland Medical Associates-Clarkston
      • Clarkston Michigan 48346 United States
      • Henry Ford Macomb Hospital-Clinton Township
      • Clinton Township Michigan 48038 United States
      • Beaumont Hospital - Dearborn
      • Dearborn Michigan 48124 United States
      • Henry Ford Medical Center-Fairlane
      • Dearborn Michigan 48126 United States
      • Henry Ford Hospital
      • Detroit Michigan 48202 United States
      • Ascension Saint John Hospital
      • Detroit Michigan 48236 United States
      • Great Lakes Cancer Management Specialists-Doctors Park
      • East China Township Michigan 48054 United States
      • Green Bay Oncology - Escanaba
      • Escanaba Michigan 49829 United States
      • Genesee Cancer and Blood Disease Treatment Center
      • Flint Michigan 48503 United States
      • Genesee Hematology Oncology PC
      • Flint Michigan 48503 United States
      • Genesys Hurley Cancer Institute
      • Flint Michigan 48503 United States
      • Hurley Medical Center
      • Flint Michigan 48503 United States
      • Helen DeVos Children's Hospital at Spectrum Health
      • Grand Rapids Michigan 49503 United States
      • Mercy Health Saint Mary's
      • Grand Rapids Michigan 49503 United States
      • Spectrum Health at Butterworth Campus
      • Grand Rapids Michigan 49503 United States
      • Academic Hematology Oncology Specialists
      • Grosse Pointe Woods Michigan 48236 United States
      • Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
      • Grosse Pointe Woods Michigan 48236 United States
      • Michigan Breast Specialists-Grosse Pointe Woods
      • Grosse Pointe Woods Michigan 48236 United States
      • Allegiance Health
      • Jackson Michigan 49201 United States
      • Bronson Methodist Hospital
      • Kalamazoo Michigan 49007 United States
      • West Michigan Cancer Center
      • Kalamazoo Michigan 49007 United States
      • Borgess Medical Center
      • Kalamazoo Michigan 49048 United States
      • Sparrow Hospital
      • Lansing Michigan 48912 United States
      • Hope Cancer Clinic
      • Livonia Michigan 48154 United States
      • Saint Mary Mercy Hospital
      • Livonia Michigan 48154 United States
      • Great Lakes Cancer Management Specialists-Macomb Medical Campus
      • Macomb Michigan 48044 United States
      • Michigan Breast Specialists-Macomb Township
      • Macomb Michigan 48044 United States
      • Saint Mary's Oncology/Hematology Associates of Marlette
      • Marlette Michigan 48453 United States
      • Toledo Clinic Cancer Centers-Monroe
      • Monroe Michigan 48162 United States
      • Mercy Health Mercy Campus
      • Muskegon Michigan 49444 United States
      • Lakeland Hospital Niles
      • Niles Michigan 49120 United States
      • Cancer and Hematology Centers of Western Michigan - Norton Shores
      • Norton Shores Michigan 49444 United States
      • Henry Ford Medical Center-Columbus
      • Novi Michigan 48377 United States
      • 21st Century Oncology-Pontiac
      • Pontiac Michigan 48341 United States
      • Hope Cancer Center
      • Pontiac Michigan 48341 United States
      • Newland Medical Associates-Pontiac
      • Pontiac Michigan 48341 United States
      • Saint Joseph Mercy Oakland
      • Pontiac Michigan 48341 United States
      • Huron Medical Center PC
      • Port Huron Michigan 48060 United States
      • Lake Huron Medical Center
      • Port Huron Michigan 48060 United States
      • Spectrum Health Reed City Hospital
      • Reed City Michigan 49677 United States
      • Great Lakes Cancer Management Specialists-Rochester Hills
      • Rochester Hills Michigan 48309 United States
      • Ascension Saint Mary's Hospital
      • Saginaw Michigan 48601 United States
      • Oncology Hematology Associates of Saginaw Valley PC
      • Saginaw Michigan 48604 United States
      • Lakeland Medical Center Saint Joseph
      • Saint Joseph Michigan 49085 United States
      • Marie Yeager Cancer Center
      • Saint Joseph Michigan 49085 United States
      • Bhadresh Nayak MD PC-Sterling Heights
      • Sterling Heights Michigan 48312 United States
      • Ascension Saint Joseph Hospital
      • Tawas City Michigan 48764 United States
      • Munson Medical Center
      • Traverse City Michigan 49684 United States
      • Advanced Breast Care Center PLLC
      • Warren Michigan 48088 United States
      • Great Lakes Cancer Management Specialists-Macomb Professional Building
      • Warren Michigan 48093 United States
      • Macomb Hematology Oncology PC
      • Warren Michigan 48093 United States
      • Michigan Breast Specialists-Warren
      • Warren Michigan 48093 United States
      • Saint John Macomb-Oakland Hospital
      • Warren Michigan 48093 United States
      • Henry Ford West Bloomfield Hospital
      • West Bloomfield Michigan 48322 United States
      • Saint Mary's Oncology/Hematology Associates of West Branch
      • West Branch Michigan 48661 United States
      • Metro Health Hospital
      • Wyoming Michigan 49519 United States
      • Huron Gastroenterology PC
      • Ypsilanti Michigan 48106 United States
      • IHA Hematology Oncology Consultants-Ann Arbor
      • Ypsilanti Michigan 48197 United States
      • Sanford Joe Lueken Cancer Center
      • Bemidji Minnesota 56601 United States
      • Fairview Ridges Hospital
      • Burnsville Minnesota 55337 United States
      • Cambridge Medical Center
      • Cambridge Minnesota 55008 United States
      • Mercy Hospital
      • Coon Rapids Minnesota 55433 United States
      • Fairview-Southdale Hospital
      • Edina Minnesota 55435 United States
      • Unity Hospital
      • Fridley Minnesota 55432 United States
      • Fairview Maple Grove Medical Center
      • Maple Grove Minnesota 55369 United States
      • Minnesota Oncology Hematology PA-Maplewood
      • Maplewood Minnesota 55109 United States
      • Saint John's Hospital - Healtheast
      • Maplewood Minnesota 55109 United States
      • Abbott-Northwestern Hospital
      • Minneapolis Minnesota 55407 United States
      • Hennepin County Medical Center
      • Minneapolis Minnesota 55415 United States
      • Health Partners Inc
      • Minneapolis Minnesota 55454 United States
      • Monticello Cancer Center
      • Monticello Minnesota 55362 United States
      • New Ulm Medical Center
      • New Ulm Minnesota 56073 United States
      • Fairview Northland Medical Center
      • Princeton Minnesota 55371 United States
      • North Memorial Medical Health Center
      • Robbinsdale Minnesota 55422 United States
      • Coborn Cancer Center at Saint Cloud Hospital
      • Saint Cloud Minnesota 56303 United States
      • Saint Cloud Hospital
      • Saint Cloud Minnesota 56303 United States
      • Park Nicollet Clinic - Saint Louis Park
      • Saint Louis Park Minnesota 55416 United States
      • Regions Hospital
      • Saint Paul Minnesota 55101 United States
      • United Hospital
      • Saint Paul Minnesota 55102 United States
      • Saint Francis Regional Medical Center
      • Shakopee Minnesota 55379 United States
      • Lakeview Hospital
      • Stillwater Minnesota 55082 United States
      • Sanford Thief River Falls Medical Center
      • Thief River Falls Minnesota 56701 United States
      • Ridgeview Medical Center
      • Waconia Minnesota 55387 United States
      • Rice Memorial Hospital
      • Willmar Minnesota 56201 United States
      • Minnesota Oncology Hematology PA-Woodbury
      • Woodbury Minnesota 55125 United States
      • Sanford Cancer Center Worthington
      • Worthington Minnesota 56187 United States
      • Fairview Lakes Medical Center
      • Wyoming Minnesota 55092 United States
      • Gulfport Memorial Hospital
      • Gulfport Mississippi 39502 United States
      • University of Mississippi Medical Center
      • Jackson Mississippi 39216 United States
      • Baptist Memorial Hospital and Cancer Center-Union County
      • New Albany Mississippi 38652 United States
      • Baptist Memorial Hospital and Cancer Center-Oxford
      • Oxford Mississippi 38655 United States
      • Baptist Memorial Hospital and Cancer Center-Desoto
      • Southhaven Mississippi 38671 United States
      • Saint Louis Cancer and Breast Institute-Ballwin
      • Ballwin Missouri 63011 United States
      • Central Care Cancer Center - Bolivar
      • Bolivar Missouri 65613 United States
      • Parkland Health Center-Bonne Terre
      • Bonne Terre Missouri 63628 United States
      • Cox Cancer Center Branson
      • Branson Missouri 65616 United States
      • Saint Francis Medical Center
      • Cape Girardeau Missouri 63703 United States
      • Southeast Cancer Center
      • Cape Girardeau Missouri 63703 United States
      • University of Missouri - Ellis Fischel
      • Columbia Missouri 65212 United States
      • Siteman Cancer Center at West County Hospital
      • Creve Coeur Missouri 63141 United States
      • Parkland Health Center - Farmington
      • Farmington Missouri 63640 United States
      • Centerpoint Medical Center LLC
      • Independence Missouri 64057 United States
      • Capital Region Southwest Campus
      • Jefferson City Missouri 65109 United States
      • Freeman Health System
      • Joplin Missouri 64804 United States
      • Mercy Hospital Joplin
      • Joplin Missouri 64804 United States
      • Truman Medical Center
      • Kansas City Missouri 64108 United States
      • Saint Luke's Hospital of Kansas City
      • Kansas City Missouri 64111 United States
      • Research Medical Center
      • Kansas City Missouri 64132 United States
      • The University of Kansas Cancer Center-North
      • Kansas City Missouri 64154 United States
      • The University of Kansas Cancer Center-Lee's Summit
      • Lee's Summit Missouri 64064 United States
      • Saint Luke's East - Lee's Summit
      • Lee's Summit Missouri 64086 United States
      • Delbert Day Cancer Institute at PCRMC
      • Rolla Missouri 65401 United States
      • Mercy Clinic-Rolla-Cancer and Hematology
      • Rolla Missouri 65401 United States
      • Heartland Regional Medical Center
      • Saint Joseph Missouri 64507 United States
      • Saint Louis Cancer and Breast Institute-South City
      • Saint Louis Missouri 63109 United States
      • Washington University School of Medicine
      • Saint Louis Missouri 63110 United States
      • Mercy Hospital South
      • Saint Louis Missouri 63128 United States
      • Siteman Cancer Center-South County
      • Saint Louis Missouri 63129 United States
      • Missouri Baptist Medical Center
      • Saint Louis Missouri 63131 United States
      • Siteman Cancer Center at Christian Hospital
      • Saint Louis Missouri 63136 United States
      • Mercy Hospital Saint Louis
      • Saint Louis Missouri 63141 United States
      • Siteman Cancer Center at Saint Peters Hospital
      • Saint Peters Missouri 63376 United States
      • Sainte Genevieve County Memorial Hospital
      • Sainte Genevieve Missouri 63670 United States
      • Mercy Hospital Springfield
      • Springfield Missouri 65804 United States
      • CoxHealth South Hospital
      • Springfield Missouri 65807 United States
      • Missouri Baptist Sullivan Hospital
      • Sullivan Missouri 63080 United States
      • Missouri Baptist Outpatient Center-Sunset Hills
      • Sunset Hills Missouri 63127 United States
      • Mercy Hospital Washington
      • Washington Missouri 63090 United States
      • Community Hospital of Anaconda
      • Anaconda Montana 59711 United States
      • Billings Clinic Cancer Center
      • Billings Montana 59101 United States
      • Saint Vincent Healthcare
      • Billings Montana 59101 United States
      • Saint Vincent Frontier Cancer Center
      • Billings Montana 59102 United States
      • Bozeman Deaconess Hospital
      • Bozeman Montana 59715 United States
      • Saint James Community Hospital and Cancer Treatment Center
      • Butte Montana 59701 United States
      • Benefis Healthcare- Sletten Cancer Institute
      • Great Falls Montana 59405 United States
      • Great Falls Clinic
      • Great Falls Montana 59405 United States
      • Saint Peter's Community Hospital
      • Helena Montana 59601 United States
      • Kalispell Regional Medical Center
      • Kalispell Montana 59901 United States
      • Saint Patrick Hospital - Community Hospital
      • Missoula Montana 59802 United States
      • Community Medical Hospital
      • Missoula Montana 59804 United States
      • Nebraska Medicine-Bellevue
      • Bellevue Nebraska 68123 United States
      • Nebraska Medicine-Village Pointe
      • Omaha Nebraska 68118 United States
      • University of Nebraska Medical Center
      • Omaha Nebraska 68198 United States
      • Carson Tahoe Regional Medical Center
      • Carson City Nevada 89703 United States
      • Cancer and Blood Specialists-Henderson
      • Henderson Nevada 89052 United States
      • Comprehensive Cancer Centers of Nevada - Henderson
      • Henderson Nevada 89052 United States
      • Comprehensive Cancer Centers of Nevada-Horizon Ridge
      • Henderson Nevada 89052 United States
      • Las Vegas Cancer Center-Henderson
      • Henderson Nevada 89052 United States
      • OptumCare Cancer Care at Seven Hills
      • Henderson Nevada 89052 United States
      • 21st Century Oncology-Henderson
      • Henderson Nevada 89074 United States
      • Comprehensive Cancer Centers of Nevada-Southeast Henderson
      • Henderson Nevada 89074 United States
      • Las Vegas Urology - Green Valley
      • Henderson Nevada 89074 United States
      • Las Vegas Urology - Pebble
      • Henderson Nevada 89074 United States
      • Urology Specialists of Nevada - Green Valley
      • Henderson Nevada 89074 United States
      • Las Vegas Urology - Pecos
      • Las Vegas Nevada 89074 United States
      • Desert West Surgery
      • Las Vegas Nevada 89102 United States
      • University Medical Center of Southern Nevada
      • Las Vegas Nevada 89102 United States
      • Hope Cancer Care of Nevada
      • Las Vegas Nevada 89103 United States
      • Cancer and Blood Specialists-Shadow
      • Las Vegas Nevada 89106 United States
      • OptumCare Cancer Care at Oakey
      • Las Vegas Nevada 89106 United States
      • Radiation Oncology Centers of Nevada Central
      • Las Vegas Nevada 89106 United States
      • Urology Specialists of Nevada - Central
      • Las Vegas Nevada 89106 United States
      • 21st Century Oncology
      • Las Vegas Nevada 89109 United States
      • HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
      • Las Vegas Nevada 89109 United States
      • Sunrise Hospital and Medical Center
      • Las Vegas Nevada 89109 United States
      • HealthCare Partners Medical Group Oncology/Hematology-San Martin
      • Las Vegas Nevada 89113 United States
      • Las Vegas Prostate Cancer Center
      • Las Vegas Nevada 89113 United States
      • Las Vegas Urology - Sunset
      • Las Vegas Nevada 89113 United States
      • Radiation Oncology Centers of Nevada Southeast
      • Las Vegas Nevada 89119 United States
      • Cancer Therapy and Integrative Medicine
      • Las Vegas Nevada 89121 United States
      • 21st Century Oncology-Vegas Tenaya
      • Las Vegas Nevada 89128 United States
      • Ann M Wierman MD LTD
      • Las Vegas Nevada 89128 United States
      • Cancer and Blood Specialists-Tenaya
      • Las Vegas Nevada 89128 United States
      • Comprehensive Cancer Centers of Nevada - Northwest
      • Las Vegas Nevada 89128 United States
      • HealthCare Partners Medical Group Oncology/Hematology-Tenaya
      • Las Vegas Nevada 89128 United States
      • Las Vegas Urology - Cathedral Rock
      • Las Vegas Nevada 89128 United States
      • Las Vegas Urology - Smoke Ranch
      • Las Vegas Nevada 89128 United States
      • OptumCare Cancer Care at MountainView
      • Las Vegas Nevada 89128 United States
      • Urology Specialists of Nevada - Northwest
      • Las Vegas Nevada 89128 United States
      • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
      • Las Vegas Nevada 89135 United States
      • Comprehensive Cancer Centers of Nevada - Town Center
      • Las Vegas Nevada 89144 United States
      • Comprehensive Cancer Centers of Nevada-Summerlin
      • Las Vegas Nevada 89144 United States
      • Summerlin Hospital Medical Center
      • Las Vegas Nevada 89144 United States
      • Las Vegas Cancer Center-Medical Center
      • Las Vegas Nevada 89148-2405 United States
      • 21st Century Oncology-Fort Apache
      • Las Vegas Nevada 89148 United States
      • Comprehensive Cancer Centers of Nevada
      • Las Vegas Nevada 89148 United States
      • OptumCare Cancer Care at Fort Apache
      • Las Vegas Nevada 89148 United States
      • Urology Specialists of Nevada - Southwest
      • Las Vegas Nevada 89148 United States
      • HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
      • Las Vegas Nevada 89149 United States
      • Comprehensive Cancer Centers of Nevada - Central Valley
      • Las Vegas Nevada 89169 United States
      • University Cancer Center
      • Las Vegas Nevada 89169 United States
      • Hope Cancer Care of Nevada-Pahrump
      • Pahrump Nevada 89048 United States
      • Renown Regional Medical Center
      • Reno Nevada 89502 United States
      • Saint Mary's Regional Medical Center
      • Reno Nevada 89503 United States
      • Radiation Oncology Associates
      • Reno Nevada 89509 United States
      • New Hampshire Oncology Hematology PA-Concord
      • Concord New Hampshire 03301 United States
      • New Hampshire Oncology Hematology PA-Hooksett
      • Hooksett New Hampshire 03106 United States
      • Memorial Sloan Kettering Basking Ridge
      • Basking Ridge New Jersey 07920 United States
      • Ocean Medical Center
      • Brick New Jersey 08724 United States
      • AtlantiCare Health Park-Cape May Court House
      • Cape May Court House New Jersey 08210 United States
      • AtlantiCare Surgery Center
      • Egg Harbor Township New Jersey 08234 United States
      • Hackensack University Medical Center
      • Hackensack New Jersey 07601 United States
      • Bayshore Community Hospital
      • Holmdel New Jersey 07733 United States
      • Southern Ocean County Medical Center
      • Manahawkin New Jersey 08050 United States
      • Memorial Sloan Kettering Monmouth
      • Middletown New Jersey 07748 United States
      • Memorial Sloan Kettering Bergen
      • Montvale New Jersey 07645 United States
      • Jersey Shore Medical Center
      • Neptune New Jersey 07753 United States
      • Riverview Medical Center/Booker Cancer Center
      • Red Bank New Jersey 07701 United States
      • Montefiore Medical Center-Einstein Campus
      • Bronx New York 10461 United States
      • Montefiore Medical Center-Weiler Hospital
      • Bronx New York 10461 United States
      • Montefiore Medical Center - Moses Campus
      • Bronx New York 10467 United States
      • James J Peters VA Medical Center
      • Bronx New York 10468 United States
      • Maimonides Medical Center
      • Brooklyn New York 11219 United States
      • Roswell Park Cancer Institute
      • Buffalo New York 14263 United States
      • Memorial Sloan Kettering Commack
      • Commack New York 11725 United States
      • Glens Falls Hospital
      • Glens Falls New York 12801 United States
      • Memorial Sloan Kettering Westchester
      • Harrison New York 10604 United States
      • Northwell Health/Center for Advanced Medicine
      • Lake Success New York 11042 United States
      • Orange Regional Medical Center
      • Middletown New York 10940 United States
      • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • New York New York 10016 United States
      • Memorial Sloan Kettering Cancer Center
      • New York New York 10065 United States
      • NYP/Weill Cornell Medical Center
      • New York New York 10065 United States
      • Rochester General Hospital
      • Rochester New York 14621 United States
      • Stony Brook University Medical Center
      • Stony Brook New York 11794 United States
      • State University of New York Upstate Medical University
      • Syracuse New York 13210 United States
      • Memorial Sloan Kettering Nassau
      • Uniondale New York 11553 United States
      • Faxton-Saint Luke's Healthcare
      • Utica New York 13502 United States
      • Dickstein Cancer Treatment Center
      • White Plains New York 10601 United States
      • Mission Hospital
      • Asheville North Carolina 28801 United States
      • Duke Cancer Institute Cary
      • Cary North Carolina 27518 United States
      • Southeastern Medical Oncology Center-Clinton
      • Clinton North Carolina 28328 United States
      • Duke University Medical Center
      • Durham North Carolina 27710 United States
      • Southeastern Medical Oncology Center-Goldsboro
      • Goldsboro North Carolina 27534 United States
      • Wayne Memorial Hospital
      • Goldsboro North Carolina 27534 United States
      • East Carolina University
      • Greenville North Carolina 27834 United States
      • Margaret R Pardee Memorial Hospital
      • Hendersonville North Carolina 28791 United States
      • Onslow Memorial Hospital
      • Jacksonville North Carolina 28546 United States
      • Southeastern Medical Oncology Center-Jacksonville
      • Jacksonville North Carolina 28546 United States
      • Duke Raleigh Hospital
      • Raleigh North Carolina 27609 United States
      • Sanford Bismarck Medical Center
      • Bismarck North Dakota 58501 United States
      • Sanford South University Medical Center
      • Fargo North Dakota 58103 United States
      • Sanford Broadway Medical Center
      • Fargo North Dakota 58122 United States
      • Sanford Roger Maris Cancer Center
      • Fargo North Dakota 58122 United States
      • Indu and Raj Soin Medical Center
      • Beavercreek Ohio 45431 United States
      • Strecker Cancer Center-Belpre
      • Belpre Ohio 45714 United States
      • Saint Elizabeth Boardman Hospital
      • Boardman Ohio 44512 United States
      • Dayton Physicians LLC-Miami Valley South
      • Centerville Ohio 45459 United States
      • Miami Valley Hospital South
      • Centerville Ohio 45459 United States
      • Adena Regional Medical Center
      • Chillicothe Ohio 45601 United States
      • Oncology Hematology Care Inc-Kenwood
      • Cincinnati Ohio 45236 United States
      • Ohio State University Comprehensive Cancer Center
      • Columbus Ohio 43210 United States
      • Mount Carmel East Hospital
      • Columbus Ohio 43213 United States
      • Columbus Oncology and Hematology Associates Inc
      • Columbus Ohio 43214 United States
      • Riverside Methodist Hospital
      • Columbus Ohio 43214 United States
      • Grant Medical Center
      • Columbus Ohio 43215 United States
      • The Mark H Zangmeister Center
      • Columbus Ohio 43219 United States
      • Mount Carmel Health Center West
      • Columbus Ohio 43222 United States
      • Doctors Hospital
      • Columbus Ohio 43228 United States
      • Good Samaritan Hospital - Dayton
      • Dayton Ohio 45406 United States
      • Miami Valley Hospital
      • Dayton Ohio 45409 United States
      • Dayton Physician LLC-Miami Valley Hospital North
      • Dayton Ohio 45415 United States
      • Miami Valley Hospital North
      • Dayton Ohio 45415 United States
      • Dayton Veterans Affairs Medical Center
      • Dayton Ohio 45428 United States
      • Delaware Health Center-Grady Cancer Center
      • Delaware Ohio 43015 United States
      • Delaware Radiation Oncology
      • Delaware Ohio 43015 United States
      • Grady Memorial Hospital
      • Delaware Ohio 43015 United States
      • Dublin Methodist Hospital
      • Dublin Ohio 43016 United States
      • Armes Family Cancer Center
      • Findlay Ohio 45840 United States
      • Blanchard Valley Hospital
      • Findlay Ohio 45840 United States
      • Orion Cancer Care
      • Findlay Ohio 45840 United States
      • Atrium Medical Center-Middletown Regional Hospital
      • Franklin Ohio 45005-1066 United States
      • Dayton Physicians LLC-Atrium
      • Franklin Ohio 45005 United States
      • Dayton Physicians LLC-Wayne
      • Greenville Ohio 45331 United States
      • Wayne Hospital
      • Greenville Ohio 45331 United States
      • Greater Dayton Cancer Center
      • Kettering Ohio 45409 United States
      • First Dayton Cancer Care
      • Kettering Ohio 45420 United States
      • Kettering Medical Center
      • Kettering Ohio 45429 United States
      • Fairfield Medical Center
      • Lancaster Ohio 43130 United States
      • OhioHealth Mansfield Hospital
      • Mansfield Ohio 44903 United States
      • Marietta Memorial Hospital
      • Marietta Ohio 45750 United States
      • OhioHealth Marion General Hospital
      • Marion Ohio 43302 United States
      • Toledo Clinic Cancer Centers-Maumee
      • Maumee Ohio 43537 United States
      • Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
      • Maumee Ohio 43537 United States
      • Knox Community Hospital
      • Mount Vernon Ohio 43050 United States
      • Licking Memorial Hospital
      • Newark Ohio 43055 United States
      • Newark Radiation Oncology
      • Newark Ohio 43055 United States
      • Mercy Health Perrysburg Cancer Center
      • Perrysburg Ohio 43551 United States
      • Southern Ohio Medical Center
      • Portsmouth Ohio 45662 United States
      • Springfield Regional Cancer Center
      • Springfield Ohio 45504 United States
      • Springfield Regional Medical Center
      • Springfield Ohio 45505 United States
      • ProMedica Flower Hospital
      • Sylvania Ohio 43560 United States
      • The Toledo Hospital/Toledo Children's Hospital
      • Toledo Ohio 43606 United States
      • Mercy Saint Anne Hospital
      • Toledo Ohio 43623 United States
      • Toledo Clinic Cancer Centers-Toledo
      • Toledo Ohio 43623 United States
      • Dayton Physicians LLC-Upper Valley
      • Troy Ohio 45373 United States
      • Upper Valley Medical Center
      • Troy Ohio 45373 United States
      • Saint Joseph Warren Hospital
      • Warren Ohio 44484 United States
      • Saint Ann's Hospital
      • Westerville Ohio 43081 United States
      • Saint Elizabeth Youngstown Hospital
      • Youngstown Ohio 44501 United States
      • Genesis Healthcare System Cancer Care Center
      • Zanesville Ohio 43701 United States
      • Cancer Centers of Southwest Oklahoma Research
      • Lawton Oklahoma 73505 United States
      • University of Oklahoma Health Sciences Center
      • Oklahoma City Oklahoma 73104 United States
      • Mercy Hospital Oklahoma City
      • Oklahoma City Oklahoma 73120 United States
      • Oklahoma Cancer Specialists and Research Institute-Tulsa
      • Tulsa Oklahoma 74146 United States
      • Saint Alphonsus Medical Center-Baker City
      • Baker City Oregon 97814 United States
      • Saint Charles Health System
      • Bend Oregon 97701 United States
      • Clackamas Radiation Oncology Center
      • Clackamas Oregon 97015 United States
      • Providence Oncology and Hematology Care Southeast
      • Clackamas Oregon 97015 United States
      • Bay Area Hospital
      • Coos Bay Oregon 97420 United States
      • Good Samaritan Hospital
      • Corvallis Oregon 97330 United States
      • Legacy Mount Hood Medical Center
      • Gresham Oregon 97030 United States
      • Providence Newberg Medical Center
      • Newberg Oregon 97132 United States
      • Saint Alphonsus Medical Center-Ontario
      • Ontario Oregon 97914 United States
      • Legacy Good Samaritan Hospital and Medical Center
      • Portland Oregon 97210 United States
      • Providence Portland Medical Center
      • Portland Oregon 97213 United States
      • Providence Saint Vincent Medical Center
      • Portland Oregon 97225 United States
      • Kaiser Permanente Northwest
      • Portland Oregon 97227 United States
      • Saint Charles Health System-Redmond
      • Redmond Oregon 97756 United States
      • Legacy Meridian Park Hospital
      • Tualatin Oregon 97062 United States
      • Lehigh Valley Hospital-Cedar Crest
      • Allentown Pennsylvania 18103 United States
      • Lehigh Valley Hospital - Muhlenberg
      • Bethlehem Pennsylvania 18017 United States
      • Christiana Care Health System-Concord Health Center
      • Chadds Ford Pennsylvania 19317 United States
      • Geisinger Medical Center
      • Danville Pennsylvania 17822 United States
      • Pocono Medical Center
      • East Stroudsburg Pennsylvania 18301 United States
      • Geisinger Medical Center-Cancer Center Hazleton
      • Hazleton Pennsylvania 18201 United States
      • Lehigh Valley Hospital-Hazleton
      • Hazleton Pennsylvania 18201 United States
      • Geisinger Medical Oncology-Lewisburg
      • Lewisburg Pennsylvania 17837 United States
      • Lewistown Hospital
      • Lewistown Pennsylvania 17044 United States
      • University of Pennsylvania/Abramson Cancer Center
      • Philadelphia Pennsylvania 19104 United States
      • Thomas Jefferson University Hospital
      • Philadelphia Pennsylvania 19107 United States
      • Fox Chase Cancer Center
      • Philadelphia Pennsylvania 19111 United States
      • Temple University Hospital
      • Philadelphia Pennsylvania 19140 United States
      • Geisinger Cancer Services-Pottsville
      • Pottsville Pennsylvania 17901 United States
      • Community Medical Center
      • Scranton Pennsylvania 18510 United States
      • Geisinger Medical Oncology-Selinsgrove
      • Selinsgrove Pennsylvania 17870 United States
      • Geisinger Medical Group
      • State College Pennsylvania 16801 United States
      • Reading Hospital
      • West Reading Pennsylvania 19611 United States
      • Geisinger Wyoming Valley/Henry Cancer Center
      • Wilkes-Barre Pennsylvania 18711 United States
      • Medical University of South Carolina
      • Charleston South Carolina 29425 United States
      • Prisma Health Cancer Institute - Laurens
      • Clinton South Carolina 29325 United States
      • Prisma Health Cancer Institute - Easley
      • Easley South Carolina 29640 United States
      • Gibbs Cancer Center-Gaffney
      • Gaffney South Carolina 29341 United States
      • Saint Francis Hospital
      • Greenville South Carolina 29601 United States
      • Prisma Health Cancer Institute - Butternut
      • Greenville South Carolina 29605 United States
      • Prisma Health Cancer Institute - Faris
      • Greenville South Carolina 29605 United States
      • Prisma Health Greenville Memorial Hospital
      • Greenville South Carolina 29605 United States
      • Saint Francis Cancer Center
      • Greenville South Carolina 29607 United States
      • Prisma Health Cancer Institute - Eastside
      • Greenville South Carolina 29615 United States
      • Prisma Health Cancer Institute - Greer
      • Greer South Carolina 29650 United States
      • Gibbs Cancer Center-Pelham
      • Greer South Carolina 29651 United States
      • Prisma Health Cancer Institute - Seneca
      • Seneca South Carolina 29672 United States
      • Spartanburg Medical Center
      • Spartanburg South Carolina 29303 United States
      • Prisma Health Cancer Institute - Spartanburg
      • Spartanburg South Carolina 29307 United States
      • MGC Hematology Oncology-Union
      • Union South Carolina 29379 United States
      • Sanford Cancer Center Oncology Clinic
      • Sioux Falls South Dakota 57104 United States
      • Avera Cancer Institute
      • Sioux Falls South Dakota 57105 United States
      • Sanford USD Medical Center - Sioux Falls
      • Sioux Falls South Dakota 57117-5134 United States
      • Wellmont Bristol Regional Medical Center
      • Bristol Tennessee 37620 United States
      • Baptist Memorial Hospital and Cancer Center-Collierville
      • Collierville Tennessee 38017 United States
      • Wellmont Medical Associates Oncology and Hematology-Johnson City
      • Johnson City Tennessee 37604 United States
      • Regional Cancer Center at Indian Path Community Hospital
      • Kingsport Tennessee 37660 United States
      • Wellmont Holston Valley Hospital and Medical Center
      • Kingsport Tennessee 37660 United States
      • Baptist Memorial Hospital and Cancer Center-Memphis
      • Memphis Tennessee 38120 United States
      • Meharry Medical College
      • Nashville Tennessee 37208 United States
      • Hendrick Medical Center
      • Abilene Texas 79601 United States
      • UT Southwestern/Simmons Cancer Center-Dallas
      • Dallas Texas 75390 United States
      • UT Southwestern/Simmons Cancer Center-Fort Worth
      • Fort Worth Texas 76104 United States
      • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
      • Houston Texas 77030 United States
      • Ben Taub General Hospital
      • Houston Texas 77030 United States
      • UT Southwestern Clinical Center at Richardson/Plano
      • Richardson Texas 75080 United States
      • American Fork Hospital / Huntsman Intermountain Cancer Center
      • American Fork Utah 84003 United States
      • Sandra L Maxwell Cancer Center
      • Cedar City Utah 84720 United States
      • Logan Regional Hospital
      • Logan Utah 84321 United States
      • Intermountain Medical Center
      • Murray Utah 84107 United States
      • McKay-Dee Hospital Center
      • Ogden Utah 84403 United States
      • Utah Valley Regional Medical Center
      • Provo Utah 84604 United States
      • Riverton Hospital
      • Riverton Utah 84065 United States
      • Dixie Medical Center Regional Cancer Center
      • Saint George Utah 84770 United States
      • Utah Cancer Specialists-Salt Lake City
      • Salt Lake City Utah 84106 United States
      • LDS Hospital
      • Salt Lake City Utah 84143 United States
      • Central Vermont Medical Center/National Life Cancer Treatment
      • Berlin Vermont 05602 United States
      • University of Vermont Medical Center
      • Burlington Vermont 05401 United States
      • University of Vermont and State Agricultural College
      • Burlington Vermont 05405 United States
      • Wellmont Medical Associates-Bristol
      • Bristol Virginia 24201 United States
      • Inova Schar Cancer Institute
      • Fairfax Virginia 22031 United States
      • Inova Fairfax Hospital
      • Falls Church Virginia 22042 United States
      • Augusta Health Center for Cancer and Blood Disorders
      • Fishersville Virginia 22939 United States
      • Bon Secours Memorial Regional Medical Center
      • Mechanicsville Virginia 23116 United States
      • Bon Secours Saint Francis Medical Center
      • Midlothian Virginia 23114 United States
      • Bon Secours DePaul Medical Center
      • Norfolk Virginia 23505 United States
      • Southwest VA Regional Cancer Center
      • Norton Virginia 24273 United States
      • Bon Secours Saint Mary's Hospital
      • Richmond Virginia 23226 United States
      • Bon Secours Cancer Institute at Reynolds Crossing
      • Richmond Virginia 23230 United States
      • Virginia Cancer Institute
      • Richmond Virginia 23230 United States
      • VCU Massey Cancer Center at Stony Point
      • Richmond Virginia 23235 United States
      • Virginia Commonwealth University/Massey Cancer Center
      • Richmond Virginia 23298 United States
      • VCU Community Memorial Health Center
      • South Hill Virginia 23970 United States
      • Providence Regional Cancer System-Aberdeen
      • Aberdeen Washington 98520 United States
      • MultiCare Auburn Medical Center
      • Auburn Washington 98001 United States
      • Virginia Mason Bainbridge Island Medical Center
      • Bainbridge Island Washington 98110 United States
      • Overlake Hospital Medical Center
      • Bellevue Washington 98004 United States
      • PeaceHealth Saint Joseph Medical Center
      • Bellingham Washington 98225 United States
      • Providence Regional Cancer System-Centralia
      • Centralia Washington 98531 United States
      • Swedish Cancer Institute-Edmonds
      • Edmonds Washington 98026 United States
      • Providence Regional Cancer Partnership
      • Everett Washington 98201 United States
      • Virginia Mason Federal Way Medical Center
      • Federal Way Washington 98002 United States
      • Tacoma/Valley Radiation Oncology Centers-Gig Harbor
      • Gig Harbor Washington 98332 United States
      • MultiCare Gig Harbor Medical Park
      • Gig Harbor Washington 98335 United States
      • Swedish Cancer Institute-Issaquah
      • Issaquah Washington 98029 United States
      • Kadlec Clinic Hematology and Oncology
      • Kennewick Washington 99336 United States
      • Northwest Cancer Clinic
      • Kennewick Washington 99336 United States
      • Seattle Cancer Care Alliance at EvergreenHealth
      • Kirkland Washington 98034 United States
      • Providence Regional Cancer System-Lacey
      • Lacey Washington 98503 United States
      • PeaceHealth Saint John Medical Center
      • Longview Washington 98632 United States
      • Virginia Mason Lynnwood Medical Center
      • Lynnwood Washington 98036 United States
      • Jefferson Healthcare
      • Port Townsend Washington 98368 United States
      • Peninsula Cancer Center
      • Poulsbo Washington 98370 United States
      • MultiCare Good Samaritan Hospital
      • Puyallup Washington 98372 United States
      • Tacoma/Valley Radiation Oncology Centers-Puyallup
      • Puyallup Washington 98372 United States
      • Valley Medical Center
      • Renton Washington 98055 United States
      • Virginia Mason Medical Center
      • Seattle Washington 98101 United States
      • Pacific Gynecology Specialists
      • Seattle Washington 98104 United States
      • Swedish Medical Center-Ballard Campus
      • Seattle Washington 98107 United States
      • Fred Hutchinson Cancer Research Center
      • Seattle Washington 98109 United States
      • Seattle Cancer Care Alliance
      • Seattle Washington 98109 United States
      • Kaiser Permanente Washington
      • Seattle Washington 98112 United States
      • Swedish Medical Center-First Hill
      • Seattle Washington 98122-4307 United States
      • Swedish Medical Center-Cherry Hill
      • Seattle Washington 98122-5711 United States
      • University of Washington Medical Center
      • Seattle Washington 98195 United States
      • PeaceHealth United General Medical Center
      • Sedro-Woolley Washington 98284 United States
      • Providence Regional Cancer System-Shelton
      • Shelton Washington 98584 United States
      • MultiCare Deaconess Cancer and Blood Specialty Center - Valley
      • Spokane Valley Washington 99216 United States
      • Rockwood Cancer Treatment Center-DHEC-Downtown
      • Spokane Washington 99204 United States
      • MultiCare Deaconess Cancer and Blood Specialty Center - North
      • Spokane Washington 99218 United States
      • Tacoma/Valley Radiation Oncology Centers-Jackson Hall
      • Tacoma Washington 97405 United States
      • Mary Bridge Children's Hospital and Health Center
      • Tacoma Washington 98405 United States
      • MultiCare Tacoma General Hospital
      • Tacoma Washington 98405 United States
      • Tacoma/Valley Radiation Oncology Centers-Saint Joe's
      • Tacoma Washington 98405 United States
      • PeaceHealth Southwest Medical Center
      • Vancouver Washington 98664 United States
      • Legacy Cancer Institute Medical Oncology and Day Treatment
      • Vancouver Washington 98684 United States
      • Legacy Salmon Creek Hospital
      • Vancouver Washington 98686 United States
      • Providence Saint Mary Regional Cancer Center
      • Walla Walla Washington 99362 United States
      • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
      • Yakima Washington 98902 United States
      • Providence Regional Cancer System-Yelm
      • Yelm Washington 98597 United States
      • West Virginia University Charleston Division
      • Charleston West Virginia 25304 United States
      • Edwards Comprehensive Cancer Center
      • Huntington West Virginia 25701 United States
      • Ascension Southeast Wisconsin Hospital - Elmbrook Campus
      • Brookfield Wisconsin 53045 United States
      • Aurora Cancer Care-Southern Lakes VLCC
      • Burlington Wisconsin 53105 United States
      • Marshfield Clinic-Chippewa Center
      • Chippewa Falls Wisconsin 54729 United States
      • Marshfield Medical Center-EC Cancer Center
      • Eau Claire Wisconsin 54701 United States
      • Mayo Clinic Health System-Eau Claire Clinic
      • Eau Claire Wisconsin 54701 United States
      • Aurora Health Center-Fond du Lac
      • Fond Du Lac Wisconsin 54937 United States
      • Ascension Saint Francis - Reiman Cancer Center
      • Franklin Wisconsin 53132 United States
      • Aurora Health Care Germantown Health Center
      • Germantown Wisconsin 53022 United States
      • Aurora Cancer Care-Grafton
      • Grafton Wisconsin 53024 United States
      • Saint Vincent Hospital Cancer Center Green Bay
      • Green Bay Wisconsin 54301 United States
      • Saint Vincent Hospital Cancer Center at Saint Mary's
      • Green Bay Wisconsin 54303 United States
      • Aurora BayCare Medical Center
      • Green Bay Wisconsin 54311 United States
      • Aurora Cancer Care-Kenosha South
      • Kenosha Wisconsin 53142 United States
      • Gundersen Lutheran Medical Center
      • La Crosse Wisconsin 54601 United States
      • Marshfield Clinic - Ladysmith Center
      • Ladysmith Wisconsin 54848 United States
      • Holy Family Memorial Hospital
      • Manitowoc Wisconsin 54221 United States
      • Aurora Bay Area Medical Group-Marinette
      • Marinette Wisconsin 54143 United States
      • Saint Vincent Hospital Cancer Center at Marinette
      • Marinette Wisconsin 54143 United States
      • Marshfield Medical Center-Marshfield
      • Marshfield Wisconsin 54449 United States
      • Community Memorial Hospital
      • Menomonee Falls Wisconsin 53051 United States
      • Aurora Cancer Care-Milwaukee
      • Milwaukee Wisconsin 53209 United States
      • Aurora Saint Luke's Medical Center
      • Milwaukee Wisconsin 53215 United States
      • Medical College of Wisconsin
      • Milwaukee Wisconsin 53226 United States
      • Aurora Sinai Medical Center
      • Milwaukee Wisconsin 53233 United States
      • Marshfield Clinic-Minocqua Center
      • Minocqua Wisconsin 54548 United States
      • Cancer Center of Western Wisconsin
      • New Richmond Wisconsin 54017 United States
      • Saint Vincent Hospital Cancer Center at Oconto Falls
      • Oconto Falls Wisconsin 54154 United States
      • Vince Lombardi Cancer Clinic - Oshkosh
      • Oshkosh Wisconsin 54904 United States
      • Ascension All Saints Hospital
      • Racine Wisconsin 53405 United States
      • Aurora Cancer Care-Racine
      • Racine Wisconsin 53406 United States
      • Marshfield Medical Center-Rice Lake
      • Rice Lake Wisconsin 54868 United States
      • HSHS Saint Nicholas Hospital
      • Sheboygan Wisconsin 53081 United States
      • Vince Lombardi Cancer Clinic-Sheboygan
      • Sheboygan Wisconsin 53081 United States
      • Marshfield Clinic Stevens Point Center
      • Stevens Point Wisconsin 54482 United States
      • Saint Vincent Hospital Cancer Center at Sturgeon Bay
      • Sturgeon Bay Wisconsin 54235-1495 United States
      • Aurora Medical Center in Summit
      • Summit Wisconsin 53066 United States
      • Vince Lombardi Cancer Clinic-Two Rivers
      • Two Rivers Wisconsin 54241 United States
      • Marshfield Clinic-Wausau Center
      • Wausau Wisconsin 54401 United States
      • Ascension Medical Group Southeast Wisconsin - Mayfair Road
      • Wauwatosa Wisconsin 53226 United States
      • Aurora Cancer Care-Milwaukee West
      • Wauwatosa Wisconsin 53226 United States
      • Aurora West Allis Medical Center
      • West Allis Wisconsin 53227 United States
      • The Alyce and Elmore Kraemer Cancer Care Center
      • West Bend Wisconsin 53095 United States
      • Marshfield Clinic - Weston Center
      • Weston Wisconsin 54476 United States
      • Marshfield Clinic - Wisconsin Rapids Center
      • Wisconsin Rapids Wisconsin 54494 United States
      • Cheyenne Regional Medical Center-West
      • Cheyenne Wyoming 82001 United States
      • Billings Clinic-Cody
      • Cody Wyoming 82414 United States
      • Welch Cancer Center
      • Sheridan Wyoming 82801 United States

      View trial on ClinicalTrials.gov


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      Published October 9, 2017
    25. Phase III Randomized Trial of Concurrent Chemoradiotherapy With or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer (Study SWOG/NRG 1806)

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      Phase III Randomized Trial of Concurrent Chemoradiotherapy With or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer (Study SWOG/NRG 1806)


      Condition: Bladder Carcinoma Infiltrating the Muscle of the Bladder Wall, Bladder Urothelial Carcinoma, Stage II Bladder Cancer AJCC v8, Stage III Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8

      Intervention:

      • Drug: Atezolizumab
      • Drug: Cisplatin
      • Drug: Fluorouracil
      • Drug: Gemcitabine
      • Drug: Mitomycin
      • Other: Quality-of-Life Assessment
      • Radiation: Radiation Therapy
      • Other: Survey Administration

      Purpose: This phase III trial studies how well chemotherapy and radiation therapy work with or without atezolizumab in treating patients with localized muscle invasive bladder cancer. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as gemcitabine, cisplatin, fluorouracil and mitomycin-C, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab with radiation therapy and chemotherapy may work better in treating patients with localized muscle invasive bladder cancer compared to radiation therapy and chemotherapy without atezolizumab.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT03775265

      Sponsor: National Cancer Institute (NCI)

      Primary Outcome Measures:

      • Measure: Bladder intact event-free survival (BI-EFS)
      • Time Frame: From the date of randomization to the first documentation of a BI-EFS event, assessed up to 5 years
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Overall survival (OS)
      • Time Frame: From date of randomization to death from any cause, assessed up to 5 years
      • Safety Issue:
      • Measure: Modified BI-EFS (mBI-EFS)
      • Time Frame: From date of randomization to the first documentation of a mBI-EFS event, assessed within 90 days
      • Safety Issue:
      • Measure: Biopsy response
      • Time Frame: At 18 weeks
      • Safety Issue:
      • Measure: Complete response duration
      • Time Frame: At 18 weeks
      • Safety Issue:
      • Measure: Progression-free survival
      • Time Frame: From date of randomization to first radiologic or histologic evidence of local progression, nodal or distant metastasis, or death due to any cause, assessed up to 5 years
      • Safety Issue:
      • Measure: Metastasis-free survival
      • Time Frame: From date of randomization to first radiologic or histologic evidence of metastatic disease or death due to any cause, assessed up to 5 years
      • Safety Issue:
      • Measure: Cancer-specific survival
      • Time Frame: From date of randomization to date of death due to bladder cancer, assessed up to 5 years
      • Safety Issue:
      • Measure: Quality of life
      • Time Frame: Baseline up to 5 years
      • Safety Issue:

      Estimated Enrollment: 475

      Study Start Date: April 19, 2019

      Phase: Phase 3

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • STEP 1 REGISTRATION:
      • If this will be the first patient from a registering site to receive a given RT modality (3DCRT vs. IMRT), the site must first submit pre-RT planning documents within 3 days of Step 1 registration and receive approval from Imaging and Radiation Oncology Core (IROC) before randomizing the patient to Step 2. If this will not be the first patient to receive a specific RT modality, the patient should be immediately randomized to Step 2 on the same day.
      • STEP 2 RANDOMIZATION
      • If patient required review of pre-RT planning, randomization must occur within 14 days of initial registration.
      • Patients must have histologically proven, T2-T4a N0M0 urothelial carcinoma of the bladder within 70 days prior to randomization. Patients with mixed urothelial carcinoma will be eligible for the trial, but the presence of small cell carcinoma will make a patient ineligible. Patients with lymph nodes >= 1.0 cm in shortest cross-sectional diameter on imaging (computed tomography [CT]/magnetic resonance imaging [MRI]) must have a biopsy of the enlarged lymph node showing no tumor involvement within 70 days prior to randomization. These patients may be suitable for neoadjuvant chemotherapy and radical cystectomy and are eligible for this trial if they seek out a bladder sparing treatment strategy, however patients who have received prior systemic chemotherapy for bladder cancer are not eligible for the trial.
      • Patients must undergo a transurethral resection of bladder tumor (TURBT) within 70 days prior to randomization. In a situation where a patient is referred from outside to the enrolling institution, patient must have a repeat cystoscopy by the urologist who will be following the patient on the clinical trial to assess the adequacy of the prior TURBT. Patient may then undergo repeat TURBT if deemed necessary as standard of care by the treating urologist. Patients may have either completely or partially resected tumors as long as the treating urologist attempted maximal resection. Patient must not have T4b disease.
      • Patients must undergo radiological staging within 70 days prior to randomization. Imaging of chest, abdomen, and pelvis must be performed using CT or MRI. Patients must not have evidence of T4bN1-3 disease. Eligibility is based on the local radiology report.
      • Patients with hydronephrosis are eligible if they have unilateral hydronephrosis and kidney function meets criteria specified.
      • Patients must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder within the previous 24 months except Ta/T1/carcinoma in situ (CIS) of the upper urinary tract including renal pelvis and ureter if the patient had undergone complete nephroureterectomy.
      • Patients must not have diffuse CIS based on cystoscopy and biopsy.
      • Patient must be planning to receive one of the protocol specified chemotherapy regimens.
      • All adverse events associated with any prior surgery and intravesical therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade =< 2 prior to randomization.
      • Patient must not have received any systemic chemotherapy for their bladder cancer.
      • Patient must not have had prior pelvic radiation.
      • Patients must not have received prior treatment for muscle invasive bladder cancer including neoadjuvant chemotherapy for the current tumor.
      • Patients must not have received any systemic therapy (including, but not limited to, interferon alfa-2b, high dose IL-2, pegylated interferon [PEG-IFN], anti-PD-1, anti-PD-L1), for non-muscle invasive bladder cancer. Prior intravesical BCG, interferon, and intravesical chemotherapy are allowed.
      • Patients must not have received any of the following prohibited therapies within 28 days prior to randomization or be planning to receive any of the following prohibited therapies during protocol treatment:
      • Anti-cancer systemic chemotherapy or biological therapy not specified in the protocol.
      • Immunotherapy not specified in this protocol.
      • Systemic or intravesical use of any non-study anti-cancer agent (investigational or non-investigational).
      • Investigational agents other than atezolizumab.
      • Live vaccines: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated vaccines, and are not allowed. Prior administration of intravesical BCG is allowed.
      • Glucocorticoids for any purpose other than to modulate symptoms from an event of suspected immunologic etiology. The use of physiologic doses of corticosteroids (defined as 10 mg prednisone) are acceptable, however site investigators should consult with the study chair for any dose higher than 10 mg prednisone. Dexamethasone 4 mg iv with chemotherapy to prevent nausea is allowed.
      • RANKL infusion: Concurrent denosumab (which binds the cytokine RANKL) for any known indication is prohibited due to interaction with study medication.
      • Patients must not have a major surgical procedure within 28 days prior to randomization. If patient had any surgical procedure then they should have recovered to full presurgical performance status and surgical adverse events should have resolved to grade =< 2. TURBT is not considered a major surgical procedure.
      • Patients must not have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to randomization. Exceptions:
      • Patients may have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea).
      • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. Physiological doses equivalent of 10 mg prednisone daily are allowed. Short term steroids given as antiemetic therapy, e.g. 4 mg dexamethasone or equivalent once a week, is allowed.
      • Patients must not have received a live, attenuated vaccine within 4 weeks prior to randomization or anticipate that such a live, attenuated vaccine will be required while on protocol treatment and up to 5 months after the last dose of protocol treatment.
      • Inactivated influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine within 4 weeks prior to randomization or while on protocol treatment and up to 5 months after the last dose of protocol treatment.
      • Patients must not have undergone prior allogeneic bone marrow transplantation or prior solid organ transplantation.
      • Patient may or may not be radical cystectomy candidates.
      • Absolute neutrophil count (ANC) >=1,500/microliter (mcL) (within 28 days prior to randomization).
      • Platelets >= 100,000/mcL (within 28 days prior to randomization).
      • Hemoglobin >= 9 g/dL (within 28 days prior to randomization).
      • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except patients with Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL) (within 28 days prior to randomization).
      • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x IULN (within 28 days prior to randomization).
      • Patients must not have clinically significant liver disease that precludes patient from treatment regimens prescribed on the study (including, but not limited to, active viral, alcoholic or other autoimmune hepatitis, cirrhosis or inherited liver disease).
      • Patients must have adequate renal function as evidenced by calculated creatinine clearance >= 25 mL/min. The creatinine used to calculate the clearance result must have been obtained within 28 days prior to randomization.
      • Patients must have Zubrod performance status =< 2.
      • Patients must have a baseline electrocardiography (ECG) performed within 30 days prior to randomization.
      • Patient must not have history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis.
      • Patients must not have an active infection requiring oral or IV antibiotics within 14 days prior to randomization. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are not eligible. If patient develops urinary tract infection after TURBT they must have recovered from the infection prior to registration.
      • Patients must not have active autoimmune disease that has required systemic treatment in past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune diseases include, but are not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, Graves' disease treated with methimazole or glomerulonephritis.
      • Patient must not have a history of active tuberculosis.
      • If patient has a known history of hepatitis B virus (HBV) or hepatitis C virus (HCV), they must meet the following criteria within 28 days prior to randomization.
      • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible.
      • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
      • Patients who are known to be positive for human immunodeficiency virus (HIV) are eligible only if they have all of the following:
      • A stable regimen of highly active anti-retroviral therapy (HAART)
      • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
      • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests within 28 days prior to randomization.
      • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for two years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible.
      • Female patients of childbearing potential must have a serum pregnancy test prior to randomization. Patients must not be pregnant or nursing due to the potential teratogenic side effects of the protocol treatment. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of protocol treatment, and for 5 months (150 days) after the last dose of all study drugs. A woman is considered to be of "reproductive potential" if she has had a menses at any time in the preceding 12 consecutive months.
      • Patients must not be known to be allergic to Chinese hamster egg or ovary cell products and must not have any known major allergic reactions to any study drug.
      • Patients must be offered the opportunity to participate in specimen banking for future studies.
      • Patients who can complete Patient-Reported Outcome instruments in English or Spanish must agree to complete the EORTC QLQ-C30, the EORTC QLQ-BLM30, the EPIC-26 (bowel domain only), and the EQ-5D-5L per protocol schedule of assessment.
      • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

      Locations:

      • Los Angeles County-USC Medical Center
      • Los Angeles California 90033 United States
      • USC / Norris Comprehensive Cancer Center
      • Los Angeles California 90033 United States
      • University of California Davis Comprehensive Cancer Center
      • Sacramento California 95817 United States
      • University of Colorado Hospital
      • Aurora Colorado 80045 United States
      • UCHealth Memorial Hospital Central
      • Colorado Springs Colorado 80909 United States
      • Memorial Hospital North
      • Colorado Springs Colorado 80920 United States
      • Shaw Cancer Center
      • Edwards Colorado 81632 United States
      • Poudre Valley Hospital
      • Fort Collins Colorado 80524 United States
      • Cancer Care and Hematology-Fort Collins
      • Fort Collins Colorado 80528 United States
      • UCHealth Greeley Hospital
      • Greeley Colorado 80631 United States
      • Medical Center of the Rockies
      • Loveland Colorado 80538 United States
      • Yale University
      • New Haven Connecticut 06520 United States
      • Mount Sinai Comprehensive Cancer Center at Aventura
      • Aventura Florida 33180 United States
      • University of Florida Health Science Center - Gainesville
      • Gainesville Florida 32610 United States
      • Mount Sinai Medical Center
      • Miami Beach Florida 33140 United States
      • Moffitt Cancer Center
      • Tampa Florida 33612 United States
      • Emory University Hospital/Winship Cancer Institute
      • Atlanta Georgia 30322 United States
      • Emory Saint Joseph's Hospital
      • Atlanta Georgia 30342 United States
      • Pali Momi Medical Center
      • 'Aiea Hawaii 96701 United States
      • The Cancer Center of Hawaii-Pali Momi
      • 'Aiea Hawaii 96701 United States
      • Queen's Medical Center
      • Honolulu Hawaii 96813 United States
      • Hawaii Oncology Inc-Kuakini
      • Honolulu Hawaii 96817 United States
      • The Cancer Center of Hawaii-Liliha
      • Honolulu Hawaii 96817 United States
      • Illinois CancerCare-Bloomington
      • Bloomington Illinois 61704 United States
      • Illinois CancerCare-Canton
      • Canton Illinois 61520 United States
      • Illinois CancerCare-Carthage
      • Carthage Illinois 62321 United States
      • Northwestern University
      • Chicago Illinois 60611 United States
      • Decatur Memorial Hospital
      • Decatur Illinois 62526 United States
      • Northwestern Medicine Cancer Center Kishwaukee
      • DeKalb Illinois 60115 United States
      • Crossroads Cancer Center
      • Effingham Illinois 62401 United States
      • Illinois CancerCare-Eureka
      • Eureka Illinois 61530 United States
      • Illinois CancerCare-Galesburg
      • Galesburg Illinois 61401 United States
      • Western Illinois Cancer Treatment Center
      • Galesburg Illinois 61401 United States
      • Northwestern Medicine Cancer Center Delnor
      • Geneva Illinois 60134 United States
      • Illinois CancerCare-Kewanee Clinic
      • Kewanee Illinois 61443 United States
      • Illinois CancerCare-Macomb
      • Macomb Illinois 61455 United States
      • Loyola University Medical Center
      • Maywood Illinois 60153 United States
      • Illinois CancerCare-Ottawa Clinic
      • Ottawa Illinois 61350 United States
      • Illinois CancerCare-Pekin
      • Pekin Illinois 61554 United States
      • Illinois CancerCare-Peoria
      • Peoria Illinois 61615 United States
      • Methodist Medical Center of Illinois
      • Peoria Illinois 61636 United States
      • Illinois CancerCare-Peru
      • Peru Illinois 61354 United States
      • Illinois CancerCare-Princeton
      • Princeton Illinois 61356 United States
      • Springfield Clinic
      • Springfield Illinois 62702 United States
      • Memorial Medical Center
      • Springfield Illinois 62781 United States
      • Mary Greeley Medical Center
      • Ames Iowa 50010 United States
      • McFarland Clinic PC - Ames
      • Ames Iowa 50010 United States
      • Medical Oncology and Hematology Associates-West Des Moines
      • Clive Iowa 50325 United States
      • Mercy Cancer Center-West Lakes
      • Clive Iowa 50325 United States
      • Greater Regional Medical Center
      • Creston Iowa 50801 United States
      • Medical Oncology and Hematology Associates-Laurel
      • Des Moines Iowa 50314 United States
      • Mercy Medical Center - Des Moines
      • Des Moines Iowa 50314 United States
      • Mercy Medical Center-West Lakes
      • West Des Moines Iowa 50266 United States
      • University of Kansas Cancer Center
      • Kansas City Kansas 66160 United States
      • University of Kansas Hospital-Westwood Cancer Center
      • Westwood Kansas 66205 United States
      • East Jefferson General Hospital
      • Metairie Louisiana 70006 United States
      • LSU Healthcare Network / Metairie Multi-Specialty Clinic
      • Metairie Louisiana 70006 United States
      • MaineHealth Coastal Cancer Treatment Center
      • Bath Maine 04530 United States
      • Waldo County General Hospital
      • Belfast Maine 04915 United States
      • MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford
      • Biddeford Maine 04005 United States
      • Stephens Memorial Hospital
      • Norway Maine 04268 United States
      • Maine Medical Center-Bramhall Campus
      • Portland Maine 04102 United States
      • Penobscot Bay Medical Center
      • Rockport Maine 04856 United States
      • MaineHealth Cancer Care Center of York County
      • Sanford Maine 04073 United States
      • MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford
      • Sanford Maine 04073 United States
      • Maine Medical Center- Scarborough Campus
      • Scarborough Maine 04074 United States
      • Maine Medical Partners - South Portland
      • South Portland Maine 04106 United States
      • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Baltimore Maryland 21287 United States
      • Saint Joseph Mercy Hospital
      • Ann Arbor Michigan 48106 United States
      • Saint Joseph Mercy Brighton
      • Brighton Michigan 48114 United States
      • Saint Joseph Mercy Canton
      • Canton Michigan 48188 United States
      • Saint Joseph Mercy Chelsea
      • Chelsea Michigan 48118 United States
      • Wayne State University/Karmanos Cancer Institute
      • Detroit Michigan 48201 United States
      • Henry Ford Hospital
      • Detroit Michigan 48202 United States
      • Weisberg Cancer Treatment Center
      • Farmington Hills Michigan 48334 United States
      • Sparrow Hospital
      • Lansing Michigan 48912 United States
      • Saint Mary Mercy Hospital
      • Livonia Michigan 48154 United States
      • Metro Health Hospital
      • Wyoming Michigan 49519 United States
      • Sanford Joe Lueken Cancer Center
      • Bemidji Minnesota 56601 United States
      • Fairview-Southdale Hospital
      • Edina Minnesota 55435 United States
      • Unity Hospital
      • Fridley Minnesota 55432 United States
      • Mayo Clinic
      • Rochester Minnesota 55905 United States
      • Parkland Health Center-Bonne Terre
      • Bonne Terre Missouri 63628 United States
      • Saint Francis Medical Center
      • Cape Girardeau Missouri 63703 United States
      • Missouri Baptist Medical Center
      • Saint Louis Missouri 63131 United States
      • Sainte Genevieve County Memorial Hospital
      • Sainte Genevieve Missouri 63670 United States
      • Missouri Baptist Sullivan Hospital
      • Sullivan Missouri 63080 United States
      • Missouri Baptist Outpatient Center-Sunset Hills
      • Sunset Hills Missouri 63127 United States
      • Nebraska Methodist Hospital
      • Omaha Nebraska 68114 United States
      • Comprehensive Cancer Centers of Nevada - Northwest
      • Las Vegas Nevada 89128 United States
      • Comprehensive Cancer Centers of Nevada
      • Las Vegas Nevada 89148 United States
      • Comprehensive Cancer Centers of Nevada - Central Valley
      • Las Vegas Nevada 89169 United States
      • Renown Regional Medical Center
      • Reno Nevada 89502 United States
      • Vidant Oncology-Kenansville
      • Kenansville North Carolina 28349 United States
      • Vidant Oncology-Kinston
      • Kinston North Carolina 28501 United States
      • Vidant Oncology-Richlands
      • Richlands North Carolina 28574 United States
      • Sanford Bismarck Medical Center
      • Bismarck North Dakota 58501 United States
      • Sanford Broadway Medical Center
      • Fargo North Dakota 58122 United States
      • Sanford Roger Maris Cancer Center
      • Fargo North Dakota 58122 United States
      • Ohio State University Comprehensive Cancer Center
      • Columbus Ohio 43210 United States
      • Kettering Medical Center
      • Kettering Ohio 45429 United States
      • University of Oklahoma Health Sciences Center
      • Oklahoma City Oklahoma 73104 United States
      • Lehigh Valley Hospital-Cedar Crest
      • Allentown Pennsylvania 18103 United States
      • Geisinger Medical Center
      • Danville Pennsylvania 17822 United States
      • Sanford Cancer Center Oncology Clinic
      • Sioux Falls South Dakota 57104 United States
      • Sanford USD Medical Center - Sioux Falls
      • Sioux Falls South Dakota 57117-5134 United States
      • Vanderbilt University/Ingram Cancer Center
      • Nashville Tennessee 37232 United States
      • UT Southwestern/Simmons Cancer Center-Dallas
      • Dallas Texas 75390 United States
      • UT Southwestern Clinical Center at Richardson/Plano
      • Richardson Texas 75080 United States
      • Augusta Health Center for Cancer and Blood Disorders
      • Fishersville Virginia 22939 United States
      • MultiCare Auburn Medical Center
      • Auburn Washington 98001 United States
      • MultiCare Gig Harbor Medical Park
      • Gig Harbor Washington 98335 United States
      • MultiCare Good Samaritan Hospital
      • Puyallup Washington 98372 United States
      • Seattle Cancer Care Alliance
      • Seattle Washington 98109 United States
      • University of Washington Medical Center
      • Seattle Washington 98195 United States
      • MultiCare Tacoma General Hospital
      • Tacoma Washington 98405 United States

      View trial on ClinicalTrials.gov


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      Published May 20, 2019
    26. Pilot Study of Celecoxib Combined With Gemcitabine and Cisplatin for Neoadjuvant Treatment of Localized, Muscle-Invasive Bladder Cancer

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      Pilot Study of Celecoxib Combined With Gemcitabine and Cisplatin for Neoadjuvant Treatment of Localized, Muscle-Invasive Bladder Cancer


      Condition: Bladder Cancer

      Intervention:

      • Drug: Celecoxib
      • Drug: Gemcitabine
      • Drug: Cisplatin

      Purpose: The purpose of this study is to compare patient tumor tissue before and after treatment with chemotherapy plus celecoxib. Investigators will look at gene expression, to see what effect celecoxib may have on tumor cells.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02885974

      Sponsor: Baylor College of Medicine

      Primary Outcome Measures:

      • Measure: mRNA expression in pre- and post-chemotherapy tissues
      • Time Frame: Up to four 21-day cycles of chemotherapy.
      • Safety Issue:
      • Measure: Number and severity of adverse events
      • Time Frame: Until 30 days after last treatment.
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: Pathological disease stage at cystectomy, including the rate of pT0 and the rate of < pT2.
      • Time Frame: At surgery, within 70 days after completing chemotherapy
      • Safety Issue:
      • Measure: Two-year progression free survival
      • Time Frame: Up to 2 years
      • Safety Issue:
      • Measure: Two-year overall survival
      • Time Frame: Up to 2 years
      • Safety Issue:

      Estimated Enrollment: 15

      Study Start Date: December 2016

      Phase: Phase 1

      Eligibility:

      • Age: minimum 18 Years maximum N/A
      • Gender: All

      Inclusion Criteria:

      • Subjects or their legally authorized representative must be informed of the investigational nature of this study, and must sign and give written informed consent in accordance with institutional and federal guidelines.
      • Patients must have histologically proven urothelial carcinoma of the bladder. Those with mixed histology, including a component of urothelial carcinoma, are eligible. Pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded.
      • Patients must have Stage cT2-T4a N0 M0 disease. Clinical T stage is based on the TURBT sample, exam under anesthesia and cross-sectional imaging studies. Patients must undergo cystoscopy and TURBT as part of the staging procedure within 120 days prior to registration. To exclude non-bulky/low-risk tumors, subjects must have documented muscle invasion with at least one of the following: i. Disease measuring at least 10 mm on cross-sectional imaging. Bladder thickening on imaging, by itself, is not adequate. ii. The presence of tumor-associated hydronephrosis.
      • Patients must have staging scans with abdominal/pelvic CT or MRI scan, and CT scan or x-ray of the chest within 56 days prior to registration. If the alkaline phosphatase is > 1.5 x upper limit of normal (ULN), there is a presence of suspicious bone pain, or if there is other clinical suspicion of bone metastases, a whole body bone scan is required within 56 days prior to registration.
      • Patients must have a Zubrod performance status of 0, 1 or 2.
      • Patients must be 18 years of age or older.
      • Patients must have adequate renal function as evidenced by calculated creatinine clearance ≥ 50 mL/min. The serum creatinine value used in the calculation must have been obtained within 28 days prior to registration.
      • Patients must have adequate hepatic function (within 28 days prior to registration), defined as: i. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (or ≤ 2.5 x ULN with Gilbert's disease); and ii. SGOT (AST) ≤ 2 x institutional ULN; and iii. SGPT (ALT) ≤ 2 x institutional ULN.
      • Patients must have adequate hematologic function (within 28 days prior to registration), defined as: i. Absolute neutrophil count (ANC) ≥ 1,500/μL; and ii. Hemoglobin ≥ 9 g/dL; and iii. Platelets ≥ 100,000/μL.
      • Patients must have tumor tissues from transurethral resection of the bladder tumor (TURBT) that is within 120 days of registration and available for submission. Tissue sample must be sufficient for IHC testing; that is,it must be sufficient tumor tissues for correlative science after pathologic diagnosis [i.e., enough tumor tissue to pass the staging criteria in 4c].
      • Patients must consent to the submission of FFPE blocks and/or unstained slides.

      Exclusion Criteria:

      • Patients must not have received previous systemic cytotoxic chemotherapy for urothelial carcinoma.
      • Patients must not have peripheral neuropathy ≥ Grade 2.
      • Patients must not have presence of Class III or IV heart failure, according to New York Heart Association Classifications, or a known left ventricular ejection fraction of less than 50%. Note: LVEF evaluation by echocardiogram or multi-gated acquisition scan (MUGA) is not required prior to registration.
      • Patients must not have a significant history of bleeding events. Patients with a history of a significant bleeding episode (e.g. hemoptysis, upper or lower GI bleeding, grade 3 or 4 gross hematuria unable to be controlled by trans-urethral resection of the bladder tumor) within 6 months of registration are not eligible.
      • No arterial thrombotic events within 6 months of registration, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the past 6 months, or myocardial infarction (MI). Patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) are ineligible. Patients who have experienced a deep venous thrombosis or pulmonary embolus within the past 6 months must be on stable therapeutic anticoagulation to be enrolled to this study.
      • In the opinion of the treating investigator, the patient must be a candidate to receive gemcitabine/cisplatin treatment.
      • Patients must not have aspirin sensitive asthma.
      • Patients must not be known to have hypersensitivity to cisplatin, gemcitabine, or celecoxib.
      • Patients must not have any incidence of or uncontrolled medical illness (e.g. active cardiac symptoms, active systemic infection, etc.) that would limit the patient's ability to participate in the protocol.
      • Patients must not be pregnant or nursing due to the potential teratogenic side effects of the protocol treatment. Women/men of reproductive potential must agree to use an effective contraceptive method during and for 6 months after completing protocol treatment. A negative pregnancy test is required within 7 days prior to registration for women of child-bearing potential.
      • Patients are ineligible if they plan on regular use of NSAIDs at any dose more than 2 times per week (on average) or aspirin at more than 325 mg at least three times per week, on average. Low-dose aspirin not exceeding 100 mg/day is permitted. Patients who agree to stop regular NSAIDs or higher dose aspirin are eligible and no wash out period is required.

      Contact:

      • Aihua Edward Yen, MD
      • 713-798-3750

      Locations:

      • Baylor Clinic
      • Houston Texas 77030 United States
      • Harris Health System - Smith Clinic
      • Houston Texas 77054 United States

      View trial on ClinicalTrials.gov


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      Published May 31, 2019
    27. Prospective Cohort Study of Transurethral Resection of Bladder Tumor (TURBT) Combined With Adjuvant Intravenous GC Chemotherapy to Prevent Moderate-high Recurrence and Progression Risks of Muscle-invasive Bladder Cancer

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      Prospective Cohort Study of Transurethral Resection of Bladder Tumor (TURBT) Combined With Adjuvant Intravenous GC Chemotherapy to Prevent Moderate-high Recurrence and Progression Risks of Muscle-invasive Bladder Cancer


      Condition: Bladder Cancer, Gemcitabine and Cisplatin Chemotherapy, Epirubicin Instillation, Recurrence, Prognosis

      Intervention:

      • Drug: Gemcitabine, cisplatin

      Purpose: It is still a challenge for urologic surgeon to prevent the post transurethral resection of bladder tumor (TURBT) recurrence of moderate-high risk non-muscle invasive bladder tumor. Adjuvant chemotherapy is a standard treatment for local progressive bladder tumor, which contains mainstream GC treatment scheme. It is common to observe clinically moderate-high risk NMIBC recurrence after routine intravesical instillation.Systematic chemotherapy can eliminate remained tumor cells especially those from mucosa basal cells so as to improve the prognosis of patients. Our clinical trial aims to investigate whether the utilization of combination of GC treatment scheme and epirubicin instillation would decrease the recurrence of moderate-high risk NMIBC.

      Study Type: Interventional

      Clinical Trials Identifier NCT 8-digits: NCT02716961

      Sponsor: The First Affiliated Hospital with Nanjing Medical University

      Primary Outcome Measures:

      • Measure: Tumor progression
      • Time Frame: Changes from post-chemotherapy to 5 years
      • Safety Issue:
      • Measure: Drug intervention complications
      • Time Frame: 2 years
      • Safety Issue:

      Secondary Outcome Measures:

      • Measure: The percent of patients transferred to radical cystectomy.
      • Time Frame: Up to 5 years
      • Safety Issue:
      • Measure: The existence of circulating tumor cells.
      • Time Frame: Before and 4 months after TURBT.
      • Safety Issue:

      Estimated Enrollment: 208

      Study Start Date: January 2016

      Eligibility:

      • Age: minimum 18 Years maximum 70 Years
      • Gender: All

      Inclusion Criteria:

      1. moderate-high risk non-muscle invasive bladder cancer patients: Multiple,recurrent, II-III grade, tumor diameter>3cm, invasive to submucosa, associated with carcinoma in situ.
      2. Normal liver and renal function.

      Exclusion Criteria:

      1. Liver and renal function deficiency (GFR<60ml/min*kg, ALT、AST>1.5*normal), lung function deficiency, heart failure, acute myocardial infarction, severe infection and trauma, major surgery and clinical hypotension and anaerobic conditions.
      2. Attending other drug experiments.
      3. Performance status, Zubrod-ECOG-WHO, ZPS≥
      4. Pregnant.
      5. Bone marrow transplantation, severe leukopenia, associated with severe infection or injury.

      Contact:

      • Qiang Lu, PhD
      • 13505196501

      Location:

      • The first affiliated hospital of Nanjing Medical University
      • Nanjing Jiangsu 210000 China

      View trial on ClinicalTrials.gov


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      Published June 29, 2017

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