Muscle Invasive Bladder Cancer Articles

Articles

  • A Feasibility Study of Durvalumab (MEDI4736) Alone or in Combination With Oleclumab (MEDI9447) as Neoadjuvant Therapy for Muscle-invasive Bladder Cancer (BLASST-2)

    {{header-clinical-trials-navigation}}

    A Feasibility Study of Durvalumab (MEDI4736) Alone or in Combination With Oleclumab (MEDI9447) as Neoadjuvant Therapy for Muscle-invasive Bladder Cancer (BLASST-2)


    Condition: Muscle Invasive Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03773666

    Sponsor: Dana-Farber Cancer Institute

    Phase: Phase 1

    Eligibility:

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

    Inclusion Criteria:

    • For inclusion in the study patients must fulfil all of the following criteria: Written informed consent and any locally-required authorization (e.g. HIPAA) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
    • Age > 18 years at time of study entry
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (See Appendix A).
    • Histologically confirmed bladder transitional cell carcinoma (TCC) ---Patients with mixed histology are required to have a component of TCC, and no component of small cell histology
    • T2-T4a N0 M0 disease, considered appropriate and planned for radical cystectomy
    • Ineligible for cisplatin-based chemotherapy, defined by any of the following:
    • Creatinine clearance (CL) <60 mL/min. GFR should be calculated from serum/plasma creatinine using the Cockcroft-gault formula.
    • CTCAE v5.0 Grade > 1 hearing loss
    • CTCAE v5.0 Grade > 1 neuropathy
    • NYHA Class > II cardiac dysfunction
    • Patients not meeting the above criteria are eligible if she/he declines perioperative cisplatin-based chemotherapy after specific informed consent describing the known benefits of cisplatin-based chemotherapy.
    • Adequate organ function laboratory values as defined below:
    • Hemoglobin ≥ 9.0 g/dL
    • Absolute neutrophil count (ANC) 1.5 x (> 1500 per mm3)
    • Platelet count ≥100 x 109/L (>75,000 per mm3)
    • Albumin > 2.5 g/dL
    • International Normalized Ratio (INR) or activated partial thromboplastin time (aPTT) < 1.5 x ULN, unless the patient is receiving anticoagulation therapy provided INR or PTT is within the therapeutic range of the intended anticoagulant therapy.
    • Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN) ---This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
    • AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal
    • Measured creatinine CL >30 mL/min or Calculated creatinine CL>30 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)
    • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
    • 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 postmenopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
    • 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 radiationinduced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
    • Patient 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.
    • Availability of baseline archival tumor tissue obtained for correlative studies dated within 8 weeks of study registration.
    • Either FFPE tumor tissue block or a minimum of fifteen 5μm unstained FFPE slides and fifteen 10μm unstained FFPE slides with an associated pathology report is required.
    • Patients without adequate baseline tumor tissue or have archival tumor tissue >8 weeks from registration must undergo cystoscopic tumor biopsy, meeting the above tissue criteria.

    Exclusion Criteria:

    • Patients with primary TCC of the ureter, urethra, or renal pelvis without TCC of the bladder
    • Inoperable tumor(s) with fixation to the pelvic wall on clinical exam
    • Any previous systemic chemotherapy or radiotherapy for TCC of bladder
    • Participation in another clinical study with an investigational product during the last 6 months
    • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional 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 intravesical chemotherapy or biologic therapy ≤ 42 days (6 weeks) prior to the first dose of study drug for patients who have received prior intravesical chemotherapy or biologic therapy (e.g. BCG)
    • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart) for durvalumab + oleclumab cohorts only. Patient safety and the cardiac EKG should be consulted as needed.
    • Any unresolved toxicity NCI CTCAE version 5.0 Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
    • Patients with Grade ≥2 neuropathy will be evaluated on a case-bycase basis after consultation with the Study Physician.
    • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab and/or oleclumab may be included only after consultation with the Study Physician.
    • Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g. hormone replacement therapy) is acceptable.
    • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
    • History of allogenic organ transplantation
    • 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:
    • Patients with vitiligo or alopecia
    • Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement
    • Any chronic skin condition that does not require systemic therapy
    • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
    • Patients with celiac disease controlled by diet alone
    • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
    • History of leptomeningeal carcinomatosis
    • Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry.
    • History of active primary immunodeficiency
    • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
    • Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug. The following are exceptions to this criterion:
    • Intranasal, inhaled, topical steroids, or local steroid injections (e.g. 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 (e.g. CT scan premedication)
    • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
    • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + oleclumab or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period
    • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
    • Prior randomization or treatment in a previous durvalumab and/or oleclumab clinical study regardless of treatment arm assignment
    • Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published March 4, 2020
  • 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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03404791

    Sponsor: Taris Biomedical LLC

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03518320

    Sponsor: Taris Biomedical LLC

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published October 13, 2018
  • A Phase 1b-2 Study of Mitomycin-c/ Capecitabine ChemoRadiotherapy Combined With Nivolumab Monotherapy or Ipilumimab and Nivolumab, as Bladder Sparing Curative Treatment for Muscle Invasive Bladder Cancer: the CRIMI Study

    {{header-clinical-trials-navigation}}

    A Phase 1b-2 Study of Mitomycin-c/ Capecitabine ChemoRadiotherapy Combined With Nivolumab Monotherapy or Ipilumimab and Nivolumab, as Bladder Sparing Curative Treatment for Muscle Invasive Bladder Cancer: the CRIMI Study


    Condition: Urinary Bladder Cancer, Invasive Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03844256

    Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

    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.
    • Be ≥ 18 years of age on day of signing informed consent.
    • Wish to preserve their bladder function or be ineligible for cystectomy.
    • Must have undergone transurethral biopsy of the bladder tumor, within 35 days of planned treatment commencement. The patient should have a histologically-confirmed diagnosis of muscle-invasive T2-T4a, N0-1M0 urothelial cell carcinoma of the bladder.
    • Must have undergone maximal transurethral resection of the bladder tumour, to an extent that is judged as safe by the urologist performing the resection, within 35 days of planned treatment commencement.
    • Subjects with tumors of mixed urothelial/non-urothelial cell histology are allowed, but urothelial cell carcinoma must be the predominant histology (>50%). Subjects with predominant or exclusively non-urothelial cell histology are not allowed.
    • Have planned for chemoradiotherapy as definitive treatment.
    • Have a performance status of 0 or 1 on the ECOG Performance Scale
    • Have a bladder function that is accessible for cystoscopical follow up.
    • Demonstrate adequate organ function. All screening labs should be performed within 28 days of registering the patient on the trial.
    • Female participants 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.
    • Female participants of childbearing potential should be willing to one highly effective method of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 month 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.
    • Male participants should agree to use condoms starting with the first dose of study therapy through 7 month after the last dose of study therapy.
    • Willing to consent to the use of their collected tumor 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:

    • Has DPD deficiency.
    • 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 may be included if the location can be safely incorporated in the radiation field.
    • Extensive or multifocal bladder carcinoma in situ (CIS) precluding curative chemoradiotherapy.
    • Evidence of distant metastatic disease on a CT or FDG PET/CT chest/abdomen/pelvis performed within 28 days prior to study entry. Up to 3 metastatic lymphnodes in the pelvis (below the common iliac arteries) are allowed, if these can be incorporated in the radiotherapy field.
    • Prior pelvic lymph-adenectomy
    • Prior pelvic radiotherapy
    • Has had prior intravenous chemotherapy, targeted small molecule therapy, or radiation therapy for treatment of bladder cancer. Prior intravesical use of BCG and MMC is permissible.
    • Unsuitable for concurrent MMC / capecitabine based ChRT based on pre-existing medical conditions.
    • 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.
    • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy over 10mg daily prednisone (or equivalent) or any other form of immunosuppressive therapy within 14 days prior to registering the patient. Patients with adrenal insufficiency receiving replacement dose steroids are allowed on the trial.
    • Has a known history of active TB (Bacillus Tuberculosis)
    • Hypersensitivity to nivolumab and/or ipilimumab or any of its excipients.
    • 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)
    • Has any history of active autoimmune disease, Stevens-Johnson syndrome or Guillain-Barre. Exceptions to this are: 1. Patients with autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone 2. Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen
    • 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 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.
    • 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 an Human Immunodeficiency Virus (HIV) infection with a PCR detectable viral load.
    • 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. 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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published January 15, 2020
  • 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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02722538

    Sponsor: Taris Biomedical LLC

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02901548

    Sponsor: H. Lee Moffitt Cancer Center and Research Institute

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published October 9, 2017
  • A Phase 3, Randomized, Double-blind Study to Evaluate Perioperative Pembrolizumab (MK-3475) + Neoadjuvant Chemotherapy Versus Perioperative Placebo + Neoadjuvant Chemotherapy in Cisplatin-eligible Participants With Muscle-invasive Bladder Cancer (KEYNOTE-

    {{header-clinical-trials-navigation}}

    A Phase 3, Randomized, Double-blind Study to Evaluate Perioperative Pembrolizumab (MK-3475) + Neoadjuvant Chemotherapy Versus Perioperative Placebo + Neoadjuvant Chemotherapy in Cisplatin-eligible Participants With Muscle-invasive Bladder Cancer (KEYNOTE-866)


    Condition: Urinary Bladder Cancer, Muscle-invasive

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03924856

    Sponsor: Merck Sharp & Dohme Corp.

    Phase: Phase 3

    Eligibility:

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

    Inclusion Criteria:

    • Have a histologically confirmed diagnosis of muscle invasive bladder cancer (T2-T4aN0M0) with predominant (≥50%) urothelial histology (histology and presence of muscle invasion to be confirmed by BICR): Participants with mixed histology are eligible provided the urothelial component is ≥50%. Participants whose tumors contain any neuroendocrine component are not eligible. Urothelial carcinomas not originating from the bladder (e.g., upper tract [ureters, renal pelvis], urethra) are not eligible.
    • Have clinically non-metastatic bladder cancer (N0M0) determined by imaging (computed tomography (CT) chest or magnetic resonance imaging (MRI) of the abdomen/pelvis.
    • Be deemed eligible for RC + PLND by his/her urologist and/or oncologist and agree to undergo curative intent standard RC + PLND (including prostatectomy if applicable).
    • Have a transurethral resection (TUR) of a bladder tumor that is submitted and adequate to determine histology, muscle invasion, and PD-L1 status by central pathology vendor.
    • Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
    • Have demonstrated adequate organ function.

    Exclusion Criteria:

    • Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions.
    • Has received any prior systemic anti-neoplastic treatment for MIBC.
    • Is cisplatin-ineligible, as defined by meeting any one of the study criteria.
    • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
    • Has received therapy with hematopoietic growth factor such as granulocyte-colony stimulating factor (G-CSF) or granulocyte-monocyte-colony stimulating factor(GM-CSF) in 14 days prior to randomization.
    • Has received prior systemic anti-cancer therapy including investigational agents within 3 years of randomization.
    • Has received any prior radiotherapy to the bladder.
    • Has received a live vaccine within 30 days prior to the first dose of study drug.
    • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
    • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
    • Has hypersensitivity to monoclonal antibodies (mAbs, including pembrolizumab) and/or any of their excipients.
    • Has severe hypersensitivity (≥Grade 3) to cisplatin and/or gemcitabine and any of their excipients.
    • Has an active autoimmune disease that has required systemic treatment in past 2 years
    • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
    • Has an active infection requiring systemic therapy.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published January 8, 2020
  • A Phase 3, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Participants With Muscle-invasive Bladder Cancer (MIBC) (KEY

    {{header-clinical-trials-navigation}}

    A Phase 3, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Participants With Muscle-invasive Bladder Cancer (MIBC) (KEYNOTE-992)


    Condition: Urinary Bladder Neoplasms

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT04241185

    Sponsor: Merck Sharp & Dohme Corp.

    Phase: Phase 3

    Eligibility:

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

    Inclusion Criteria:

    • Has a histologically confirmed diagnosis of MIBC with predominant urothelial histology
    • Has clinically non-metastatic bladder cancer (N0M0)
    • Has planned and is eligible to receive chemoradiotherapy (CRT) and one of the protocol-specified radiosensitizing chemotherapy regimens
    • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
    • Demonstrates adequate organ function
    • Male participants are eligible to participate if they agree to the following during the intervention period and for at least 180 days after the last dose of study intervention:
    • Refrain from donating sperm
    • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception unless confirmed to be azoospermic
    • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
    • Is not a woman of childbearing potential (WOCBP)
    • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 180 days after the last dose of study intervention; and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period

    Exclusion Criteria:

    • Has the presence of diffuse carcinoma in situ (CIS) (multiple foci of CIS) throughout the bladder
    • Has the presence of urothelial carcinoma (UC) at any site outside of the urinary bladder in the previous 2 years except for Ta stage/T1 stage/CIS of the upper tract if the participant has undergone a complete nephroureterectomy
    • Has a known additional malignancy that is progressing or has required active therapy within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or other carcinoma in situ that has undergone potentially curative therapy
    • Has the presence of bilateral hydronephrosis
    • Has limited bladder function with frequency of small amounts of urine (< 30 mL), urinary incontinence, or requires self-catheterization or a permanent indwelling catheter
    • Has received prior pelvic/local radiation therapy or any antineoplastic treatment for muscle-invasive bladder cancer (MIBC). Treatment for non-muscle invasive bladder cancer (NMIBC) with intravesical instillation therapy that was completed ≥28 days prior to randomization is allowed. Prior systemic treatment of NMIBC is not permitted.
    • Received prior therapy with an anti-PD-1 (programmed cell death protein 1), anti-PD-L1 (programmed death-ligand 1), or anti-PD-L2 (programmed cell death 1 ligand 2), or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4 [cytotoxic T-lymphocyte-associated protein 4], OX 40, or CD137 [cluster of differentiation 137])
    • Has received a live vaccine within 30 days prior to the first dose of study drug
    • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
    • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or the selected chemotherapy regimen, and/or any of their excipients
    • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
    • Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, 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) is not considered a form of systemic treatment and is allowed
    • Has a history of non-infectious pneumonitis that required steroids or has current pneumonitis
    • Has an active infection requiring systemic therapy
    • Has a known history of human immunodeficiency virus (HIV) infection
    • Has a known history of Hepatitis B or known active Hepatitis C virus infection
    • Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
    • Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
    • Has had an allogenic tissue/solid organ transplant

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published May 20, 2020
  • 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-

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03661320

    Sponsor: Bristol-Myers Squibb

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    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

    {{header-clinical-trials-navigation}}

    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 Bacillus Calmette-Guerin (BCG)


    Condition: Urinary Bladder Neoplasms

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03258593

    Sponsor: National Cancer Institute (NCI)

    Phase: Phase 1

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • 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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    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)

    {{header-clinical-trials-navigation}}

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


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03171025

    Sponsor: University of Utah

    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. Patients who have M1 disease at any time prior to start of treatment are not eligible.
    • 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 adenocarcinoma, transitional, squamous-cell, or sarcomatoid carcinoma primary of the bladder, urethra, or lower ureter.
    • 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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published October 9, 2017
  • A Phase II Study Investigating Preoperative MPDL3280A in Operable Transitional Cell Carcinoma of the Bladder (ABACUS)

    {{header-clinical-trials-navigation}}

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


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02662309

    Sponsor: Queen Mary University of London

    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

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02145390

    Sponsor: University of Miami

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02451423

    Sponsor: Lawrence Fong

    Phase: Phase 2

    Eligibility:

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

    Inclusion Criteria:

    • 18 years of age or older
    • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1
    • Histologically document transitional cell carcinoma with the presence of any of the following stages: Carcinoma in situ (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 transitional cell carcinoma (TCC) pattern.
    • For subjects with non-muscle-invasive bladder cancer (NMIBC), Bacillus Calmette-Guerin (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. Glomerular filtration rate (GFR) should be assessed by calculation from serum/plasma creatinine (Cockcroft-Gault formula)
    • Common Terminology Criteria for Adverse Events (CTCAE) Grade >/= 2 hearing loss
    • CTCAE Grade >/= 2 neuropathy
    • Subjects with nonmetastatic muscle-invasive bladder cancer (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
    • White Blood Cell count (WBC) > 2500 cells/mm3
    • Absolute Neutrophil Count (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)
    • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limit of normal (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 lymphadenectomy 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 (HBcAb) 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 Urological Cancers (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 Prostate-specific antigen (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).

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02621151

    Sponsor: NYU Langone Health

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03049410

    Sponsor: University College, London

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT01224665

    Sponsor: Southwest Oncology Group

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02450331

    Sponsor: Hoffmann-La Roche

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published October 13, 2018
  • 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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03732677

    Sponsor: AstraZeneca

    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 and mixed transitional cell histology - Patients must be planning to undergo a radical cystectomy - 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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02812420

    Sponsor: M.D. Anderson Cancer Center

    Phase: Early 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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02989584

    Sponsor: Memorial Sloan Kettering Cancer Center

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published October 9, 2017
  • A Pilot Study of 18Fluorine-Fluciclovine Positron Emission Tomography/Computed Tomography for Staging Muscle Invasive Bladder Cancer Preceding Radical Cystectomy

    {{header-clinical-trials-navigation}}

    A Pilot Study of 18Fluorine-Fluciclovine Positron Emission Tomography/Computed Tomography for Staging Muscle Invasive Bladder Cancer Preceding Radical Cystectomy


    Condition: Bladder Cancer, Urothelial Carcinoma

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT04018053

    Sponsor: Dana-Farber Cancer Institute

    Phase: Early Phase 1

    Eligibility:

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

    Inclusion Criteria:

    • Participants must have histologically or cytologically confirmed urothelial carcinoma of the bladder.
    • Participants must have cT2-T4N0 disease at the time of the study, as defined by conventional CT or MRI imaging. Patients must have no definite evidence of locoregional or distant metastatic disease at the time of study eligibility, as defined by conventional imaging.
    • Radical cystectomy must be planned for the patient after the planned 18F-fluciclovine-PET/CT.
    • Patients may or may not have had prior neoadjuvant therapy prior to this study.
    • Age ≥18 years. Since no dosing or adverse event data are currently available on the use of 18F-fluciclovine in participants <18 years of age, and the majority of bladder cancer occur in the adult population [42], children are excluded from this study but will be eligible for future pediatric trials.
    • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
    • Ability and willingness to comply with the study procedures.
    • The effects of 18F-fluciclovine on the developing human fetus are unknown. For this reason and because radiopharmaceuticals may be teratogenic, women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for 24 hours after the PET/CT scan is completed. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Ability to understand and the willingness to sign a written informed consent document

    Exclusion Criteria:

    • Participants with other known malignancies.
    • Pregnant women are excluded from this study because 18F-fluciclovine is a radiopharmaceutical with the potential for teratogenic effects. Because of the radiation exposure to a nursing infant from 18F-fluciclovine, women who are breastfeeding are also excluded from this study.
    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to 18F-fluciclovine.
    • 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.
    • Contraindications for PET/CT including: --Severe claustrophobia
    • Any past or current condition that in the opinion of the study investigators would confound the results of the study or pose additional risk to the patient by their participation in the study

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published January 13, 2020
  • 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)

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03520491

    Sponsor: Memorial Sloan Kettering Cancer Center

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02447549

    Sponsor: Institute of Cancer Research, United Kingdom

    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)

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02177695

    Sponsor: Southwest Oncology Group

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • A Randomized Phase II Trial Assessing Trimodality Therapy With or Without Adjuvant Durvalumab to Treat Patients With Muscle-Invasive Bladder Cancer

    {{header-clinical-trials-navigation}}

    A Randomized Phase II Trial Assessing Trimodality Therapy With or Without Adjuvant Durvalumab to Treat Patients With Muscle-Invasive Bladder Cancer


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03768570

    Sponsor: Canadian Cancer Trials Group

    Phase: Phase 2

    Eligibility:

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

    Inclusion Criteria:

    • Histologic diagnosis of urothelial carcinoma of the bladder. Patients with mixed histology and focal differentiation are eligible but patients with pure small cell histology will be excluded.
    • Stage T2-T4a N0M0 at time of diagnosis based on trans-urethral resection of bladder tumour, imaging, and/or bimanual examination under anesthesia.
    • CT scan of the chest/abdomen/pelvis within 8 weeks from enrollment, showing no evidence of metastatic disease.
    • Patients must be ≥ 18 years of age.
    • Patients must have a life expectancy greater than 6 months.
    • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and a body weight of > 30kg.
    • Patients must have adequate hematologic reserve: Platelet count ≥ 75 x 10^9/L, Absolute neutrophils ≥ 1.0 x 10^9/L. Anemia will be corrected to minimum hemoglobin of 90 g/L with red cell transfusions, if necessary.
    • Patients must have an estimated creatinine clearance (Cockcroft-Gault Equation) ≥ 30 ml/min.
    • Patients must have adequate liver function with a bilirubin ≤ 1.5 ULN (if confirmed Gilbert's, eligible providing bilirubin ≤ 3 x UNL) and AST/ALT (SGOT/SGPT) < 2.5 x the upper normal limit.
    • All patients must have a tumour block from their primary tumour available and consent to release the block/cores/cut slides for correlative analyses ( and the centre/pathologist must have agreed to the submission of the specimen(s).
    • Patients have completed prior trimodality therapy (TMT) consisting of surgery, chemotherapy and radiation therapy treatment prior to enrollment. Patient should start treatment within 42 days after completion of TMT.
    • Patients must have undergone a transurethral resection prior to study enrollment.
    • Patient may have completed up to 4 cycles of cisplatin-based neo-adjuvant chemotherapy. Adjuvant chemotherapy is not permitted. Patients will have received cisplatin, given intravenously during the radiation therapy. OR Patients may have received fluorouracil and mitomycin given intravenously once weekly or gemcitabine as an alternative to cisplatin during radiotherapy.
    • The following are radiotherapy guidelines for patients treated on study. Patients will be treated to radical treatment doses using IMRT, VMAT or 4 field conformal techniques. Planning will be based on CT planning. IGRT is recommended during the radiotherapy treatment. Recognizing differences in usual radiotherapy doses used in the various participating countries and centres the following would be acceptable doses in this study. The bladder CTV will include the whole empty bladder and any extravesical extension. PTV expansion will be a minimum of 0.75 cm right, left and inferiorly, 1.5 cm Anteriorly and superiorly and 1 cm posteriorly. These minimum expansions are with Cone beam verification. For patients undergoing RT without image-guided verification 1.5 cm expansion in all directions is recommended. Acceptable doses for this study include:
    • Bladder only: 64-66 Gy in 32-33 fractions over 6.5 weeks; 50-55 Gy in 20 fractions over 4 weeks
    • Pelvis and bladder: 45-46 Gy to pelvic nodes + 17-20 Gy bladder boost in 33-35 fractions over 6.5-7 wks [Note: minimal nodal dose (if used) is 44 Gy in 32f or 40 Gy in 20f]
    • Patients receiving concurrent bladder boost: pelvis dose 40 Gy and bladder dose 50 Gy given in 20 fractions over 4 weeks. Adaptive radiotherapy techniques would be acceptable.
    • Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English, French or Spanish.
    • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
    • Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits placed on patients being considered for this trial.
    • In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient enrollment.
    • Women/men of childbearing potential must have agreed to use a highly effective contraceptive method during and for 3 months following treatment.
    • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

    Exclusion Criteria:

    • Pre-existing medical conditions precluding treatment.
    • Pregnancy or lactating mothers.
    • Received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, including durvalumab anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumour Necrosis Factor Receptor [TNFR] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
    • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn's disease: not due to radiation reaction), diverticulitis with the exception of diverticulosis, celiac disease (controlled by diet alone) or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
    • Patients with alopecia;
    • Patients with Grave's disease, vitiligo or psoriasis not requiring systemic treatment (within the last 2 years);
    • Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement;
    • Any chronic skin condition that does not require systemic therapy.
    • Patients with active or uncontrolled intercurrent illness including, but not limited to:
    • cardiac dysfunction (symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia);
    • active peptic ulcer disease or gastritis;
    • active bleeding diatheses;
    • psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent;
    • known history of previous clinical diagnosis of tuberculosis;
    • known active human immunodeficiency virus infection (positive HIV 1/2 antibodies). HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible;
    • known active hepatitis B infection (positive HBV surface antigen (HBsAg). Patients with a past or resolved HBV infection (defined as presence of hepatitis B core antibody (anti-HBc) and absence of HBsAg) are eligible;
    • known active hepatitis C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
    • History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy or grade ≥ 3 infusion reaction.
    • Current or prior use of immunosuppressive medication within 28 days of study entry, with the exceptions of intranasal and inhaled corticosteroids or systemic chronic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Corticosteroids used on study for anti-emetic purpose are allowed. Corticosteroids as premedication for hypersensitivity reactions (e.g. computed tomography [CT] scan premedication) are allowed.
    • Peripheral neuropathy ≥ grade 2 (CTCAE v5.0).
    • History of allergic or hypersensitivity reactions to any study drug or their excipients.
    • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec in screening ECG measured using standard institutional method or history of familial long QT syndrome.
    • History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline CT scan.
    • Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
    • Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.
    • Live attenuated vaccination administered within 30 days prior to randomization.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published March 5, 2020
  • A Randomized Phase II Trial Evaluating an Organ-conserving Strategy With Radiotherapy + CDDP + Gemcitabine vs Radiotherapy + CDDP in Muscle-infiltrative Bladder Cancer

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT01495676

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

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    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)

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02170090

    Sponsor: Universitätsklinikum Hamburg-Eppendorf

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • Adjuvant Radiotherapy After Cystectomy for Patients With Muscle Invasive Bladder Cancer: a Phase II Trial.

    {{header-clinical-trials-navigation}}

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


    Condition: Toxicity

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02397434

    Sponsor: University Hospital, Ghent

    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:

    1. -

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published January 25, 2017
  • 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)

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02546661

    Sponsor: AstraZeneca

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • Application-based Perioperative Management of the Radical Cystectomy Patient

    {{header-clinical-trials-navigation}}

    Application-based Perioperative Management of the Radical Cystectomy Patient


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02942121

    Sponsor: University of Kansas Medical Center

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • 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
  • 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
  • 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
  • Ethacrynic Acid Elimination in Non-Muscle Invasive Bladder Cancer Patients Undergoing Transurethral Resection

    {{header-clinical-trials-navigation}}

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


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02852564

    Sponsor: Eugene Lee, MD

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • Identification and Treatments of Basal Like Bladder Cancer (Study on Human Tumor Samples and Animal Models)

    {{header-clinical-trials-navigation}}

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


    Condition: Muscle Invasive Bladder Cancer, Molecular Taxonomy

    Study Type: Observational

    Clinical Trials Identifier NCT 8-digits: NCT02648100

    Sponsor: Assistance Publique - Hôpitaux de Paris

    Phase:

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • Impact of Positron Emission Tomography (PET) Imaging in Muscle-invasive Urothelial Carcinoma of the Bladder Staging

    {{header-clinical-trials-navigation}}

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


    Condition: Muscle-invasive Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02462239

    Sponsor: Ontario Clinical Oncology Group (OCOG)

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • Improving Clinical Staging for Muscle Invasive Bladder Cancer Through Molecular Profiling and Improved Imaging

    {{header-clinical-trials-navigation}}

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


    Condition: Bladder Cancer

    Study Type: Observational

    Clinical Trials Identifier NCT 8-digits: NCT02203136

    Sponsor: M.D. Anderson Cancer Center

    Phase:

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • LCCC 1209: Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography-Magnetic Resonance Imaging (FDG-PET-MRI) for Staging of Muscle-Invasive Bladder Cancer

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT01655745

    Sponsor: UNC Lineberger Comprehensive Cancer Center

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published January 25, 2017
  • Lymphadenectomy in Urothelial Carcinoma in the Renal Pelvis and Ureter

    {{header-clinical-trials-navigation}}

    Lymphadenectomy in Urothelial Carcinoma in the Renal Pelvis and Ureter


    Condition: Ureteral Neoplasms

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02607709

    Sponsor: Zealand University Hospital

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • MDSC Clinical Assay for Cancer Detection and Monitoring in Bladder Carcinoma

    {{header-clinical-trials-navigation}}

    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

    Study Type: Observational

    Clinical Trials Identifier NCT 8-digits: NCT02735512

    Sponsor: University of Southern California

    Phase:

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • Muscle Invasive Bladder Cancer: External Beam Radiotherapy as an Alternative for Cystectomy

    {{header-clinical-trials-navigation}}

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


    Condition: Toxicity

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02748200

    Sponsor: University Hospital, Ghent

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • Neoadjuvant Gemcitabine, Cisplatin, Plus Nivolumab in Patients With Muscle-invasive Bladder Cancer With Selective Bladder Sparing

    {{header-clinical-trials-navigation}}

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


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03558087

    Sponsor: Matthew Galsky

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published November 20, 2018
  • 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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02449239

    Sponsor: Viventia Bio

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer

    {{header-clinical-trials-navigation}}

    Pembrolizumab With Chemoradiotherapy as Treatment for Muscle Invasive Bladder Cancer


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02662062

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

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published February 13, 2017
  • Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations (PROOF 302)

    {{header-clinical-trials-navigation}}

    Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations (PROOF 302)


    Condition: Upper Tract Urothelial Carcinomas, Urothelial Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT04197986

    Sponsor: QED Therapeutics, Inc.

    Phase: Phase 3

    Eligibility:

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

    Inclusion Criteria:

    • 1. Have histologically or cytologically confirmed, invasive urothelial carcinoma with susceptible FGFR3 alterations within 120 days following nephroureterectomy, distal ureterectomy, or cystectomy 2. If the patient received neoadjuvant chemotherapy, pathologic stage at surgical resection must be AJCC Stage ≥ ypT2 and/or yN+. 3. If the patient did not receive neoadjuvant chemotherapy: 1. Must be ineligible to receive cisplatin-based adjuvant chemotherapy per the Galsky criteria:
    • creatinine clearance < 60cc/min or
    • ≥ Grade 2 hearing loss or
    • ≥ Grade 2 neuropathy) 2. Pathologic stage must be AJCC Stage ≥pT2 pN0-2 M0 (post-lymphadenectomy or no lymphadenectomy [pNx]) for upper tract disease. 3. Pathologic stage should be AJCC Stage ≥pT3 or pN+ (bladder cancer). 4. Have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. 5. Patients must have no evidence of metastatic disease based on screening CT or MRI.

    Exclusion Criteria:

    1. Presence of positive surgical margins following nephroureterectomy, distal ureterectomy, or cystectomy.
    2. Have received Bacillus Calmette-Guerin (BCG) or other intravesical therapy for Non-Muscle Invasive Bladder Cancer (NMIBC) within the previous 30 days.
    3. Have previously or currently is receiving treatment with a mitogen-activated protein kinase (MEK) or selective FGFR inhibitor.
    4. Have impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (eg, active ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
    5. Have current evidence of corneal or retinal disorder/keratopathy.
    6. Have a history and/or current evidence of extensive tissue calcification.
    7. Have current evidence of endocrine alterations of calcium/phosphate homeostasis (eg, parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis), unless well controlled.
    8. Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration.
    9. Clinically significant cardiac disease.
    10. Recent (< 3 months prior to first dose of study drug) transient ischemic attack or stroke.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published May 20, 2020
  • Phase I Dose-Escalation Study of Image-Guided Radiation Therapy for Bladder-Cancer Patients Undergoing Radiotherapy and Concurrent Gemcitabine Chemotherapy

    {{header-clinical-trials-navigation}}

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


    Condition: Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT01104350

    Sponsor: Memorial Sloan Kettering Cancer Center

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published December 12, 2016
  • Phase I Study of Hypofractionated Radiotherapy and Anti-PD1 Antibody (Pembrolizumab) in the Treatment of Advanced Bladder Cancer

    {{header-clinical-trials-navigation}}

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


    Condition: Invasive Bladder Cancer

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02560636

    Sponsor: Royal Marsden NHS Foundation Trust

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • 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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02365766

    Sponsor: Christopher Hoimes, M.D.

    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.

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • 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

    {{header-clinical-trials-navigation}}

    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

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02690558

    Sponsor: UNC Lineberger Comprehensive Cancer Center

    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

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017

Page 1 of 2