Bladder Cancer

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


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

Intervention:

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

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03518320

Sponsor: Taris Biomedical LLC

Primary Outcome Measures:

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

Estimated Enrollment: 25

Study Start Date: January 2, 2019

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

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

Exclusion Criteria:

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

Contact:

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

Locations:

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

View trial on ClinicalTrials.gov


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Phase II Study of Pembrolizumab (MK-3475) as First-Line Therapy for High Risk T1 Non-Muscle-Invasive Bladder Cancer


Condition: Bladder Cancer

Intervention:

  • Drug: Pembrolizumab (MK-3475)

Purpose: The purpose of this study is to find out what effects, good and/or bad, pembrolizumab has on the participant and urothelial cancer.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03504163

Sponsor: Memorial Sloan Kettering Cancer Center

Primary Outcome Measures:

  • Measure: The proportion of patients who are disease-free
  • Time Frame: 6 months
  • Safety Issue:

Estimated Enrollment: 37

Study Start Date: June 27, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Be willing and able to provide written informed consent/assent for the trial.
  • Histologically confirmed urothelial cancer by TURBT performed at MSKCC.
  • TURBT within 6 weeks of protocol entry with complete resection of all papillary lesions.
  • Patients with high risk, BCG-naïve non-muscle-invasive urothelial cancer defined as having one of the following disease states:
  • T1 on restaging biopsy, plus cis
  • Multiple (≥ 1) T1 recurrences, plus cis
  • Multifocal T1 plus cis
  • T1b, plus cis
  • T1 with lymphovascular invasion plus cis
  • Patient refusal of cystectomy and bilateral pelvic lymphadenectomy
  • No prior intravesical therapy.
  • No prior radiation therapy for bladder cancer. Prior radiation therapy for prostate cancer is allowed.
  • ECOG performance status 0 or 1.
  • Age ≥ 18 years of age
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control, be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of the study medication (reference section 9.5.2). 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.
  • Patients must not have other invasive malignancies within the past 5 years (with the exception of non-melanoma skin cancers, localized prostate cancer, and carcinoma in situ of the cervix).
  • Required Initial Laboratory Values:
  • Absolute neutrophil count ≥ 1.5 x 10E9/L
  • Platelets ≥ 100 x 10E9/L
  • Hemoglobin ≥ 9 g/dL
  • Bilirubin ≤ 1.5 times the upper limit of normal (x ULN)
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN
  • Calculated creatinine clearance ≥ 30 using the CKD-Epi formula

Exclusion Criteria:

  • Prior treatment with systemic chemotherapy
  • 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
  • Presence of any systemic metastases (ie, nodal, visceral, or central nervous system)
  • Major surgical procedure (other than TURBT) within 28 days prior to the study
  • Pregnant (positive pregnancy test) or lactating
  • Serious, non-healing wound, ulcer, or bone fracture
  • Inability to comply with study and/or follow-up procedures
  • Prior therapy with an anti-PD-1 agent, anti-PD-L1 agent, or other inhibitory or stimulatory agent oriented towards a T-cell receptor
  • Active infection requiring systemic therapy
  • Known history of human immunodeficiency virus (HIV)
  • Known active Hepatitis B or Hepatitis C
  • Received live attenuated vaccines within 30 days prior to start of study treatment. Patients must also agree to avoid live attenuated vaccines during study treatment.
  • 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 or immunosuppressive agents. Subjects with vitiligo, diabetes Type I, or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjøgren's syndrome will not be excluded from the study.

Contact:

  • Dean Bajorin, MD
  • 646-422-4333

Location:

  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States

View trial on ClinicalTrials.gov


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An Open-Label, Multi-Center Trial of INO-5401 + INO-9012 in Combination With Atezolizumab in Subjects With Locally Advanced Unresectable or Metastatic/Recurrent Urothelial Carcinoma


Condition: Urothelial Carcinoma

Intervention:

  • Biological: INO-5401
  • Biological: INO-9012
  • Drug: Atezolizumab
  • Device: CELLECTRA™ 2000

Purpose: This is a Phase I/IIA, open-label, multi-center trial to evaluate the safety, immunogenicity and preliminary clinical efficacy of INO-5401 + INO-9012 delivered by intramuscular (IM) injection followed by electroporation (EP), in combination with atezolizumab in participants with locally advanced unresectable or metastatic/recurrent Urothelial Carcinoma (UCa). The trial population is divided into two cohorts: Cohort A: Participants with locally advanced unresectable or metastatic/recurrent UCa, who have confirmed disease progression during or following treatment with anti-Programmed Death receptor-1/Programmed Death receptor Ligand-1 (anti-PD-1/PD-L1) therapy; Cohort B: Participants with locally advanced unresectable or metastatic/recurrent UCa, who are treatment naïve and ineligible for cisplatin-based chemotherapy. A safety run-in will be performed with up to six participants (safety analysis participants) from cohort A.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03502785

Sponsor: Inovio Pharmaceuticals

Primary Outcome Measures:

  • Measure: Number of Adverse Events
  • Time Frame: From baseline up to 90 days after last dose of study medication (up to approximately 2 years and 3 months)
  • Safety Issue:
  • Measure: Antigen-Specific Cellular Immune Response
  • Time Frame: At baseline, Weeks 3, 6, 9, 12 and every 12 weeks thereafter up to end of study (up to approximately 2 years)
  • Safety Issue:
  • Measure: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator Review in Cohort A
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: ORR by RECIST version 1.1 by Investigator Review in Cohort B
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:
  • Measure: ORR by Immune RECIST (iRECIST)
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:
  • Measure: Duration of Response (DoR)
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:
  • Measure: Progression Free Survival (PFS) as Assessed by RECIST version 1.1 and iRECIST
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:
  • Measure: Overall Survival (OS)
  • Time Frame: : From Baseline to the time of death from any cause (up to approximately 2 years)
  • Safety Issue:

Estimated Enrollment: 85

Study Start Date: May 24, 2018

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • Sign an Informed Consent Form (ICF);
  • Have histologically or cytologically documented locally advanced unresectable or metastatic/recurrent urothelial carcinoma (including renal pelvis, ureters, urinary bladder, and urethra);
  • For Cohort A: Subjects who have radiographically confirmed disease progression during or following treatment with an anti-PD-1/PD-L1 based therapy;
  • For Cohort B: No prior chemotherapy for inoperable locally advanced or metastatic or recurrent UCa and ineligible ("unfit") for cisplatin-based chemotherapy;
  • Have measurable disease, as defined by RECIST version 1.1;
  • Have a performance status of 0 or 1 on Eastern Cooperative Oncology Group (ECOG) Performance Scale;
  • Have life expectancy of >/= 3 months;
  • Be willing to provide a tissue sample for pre-treatment intra-tumoral assessment of proinflammatory and immunosuppressive factors;
  • Have electrocardiogram (ECG) with no clinically significant findings as assessed by the investigator performed within 28 days prior to first dose;
  • Demonstrate adequate hematological, renal, hepatic, and coagulation function;
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of study treatment;
  • For male subjects: agreement not to father a child. Participants must be surgically sterile (e.g, vasectomy) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of study treatment.

Exclusion Criteria:

  • Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day 0 as well as current participation or recipient of treatment on a clinical trial within 28 days prior to Day 0;
  • Documented active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis;
  • Malignancies other than UCa within 3 years prior to Day 0, with the exception of those with negligible risk of metastasis or death treated with expected curative outcome;
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies;
  • Treatment with systemic immunostimulatory agents;
  • Treatment with systemic immunosuppressive medication;
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins;
  • Known hypersensitivity allergy or contraindication to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the PD-1/PD-L1 inhibitor formulation;
  • Active or history of autoimmune disease or immune deficiency;
  • History or any evidence of interstitial lung disease;
  • History of human immunodeficiency virus (HIV);
  • Active hepatitis B or active hepatitis C;
  • Severe infections within 4 weeks prior to enrollment;
  • Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 0;
  • 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 negatively impacted by EP treatment, or is not in the best interest of the subject to participate in the opinion of the treating investigator;
  • Prior allogeneic stem cell or solid organ transplant;
  • Uncontrolled tumor-related pain; pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures; or, hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.

Contact:

  • Inovio Call Center
  • 267-440-4237

Locations:

  • Alaska Clinical Research Center, LLC
  • Anchorage Alaska 99503 United States
  • Mayo Clinic Cancer Center
  • Phoenix Arizona 85054 United States
  • H. Lee Moffitt Cancer Center & Research Institute, Inc.
  • Tampa Florida 33612 United States
  • Indiana University Simon Cancer Center
  • Indianapolis Indiana 46202 United States
  • University of Kansas Cancer Center and Medical Pavilion
  • Westwood Kansas 66205 United States
  • Johns Hopkins University School of Medicine
  • Baltimore Maryland 21287 United States
  • Karmanos Cancer Institute
  • Detroit Michigan 48201 United States
  • Washington University School of Medicine in St. Louis
  • Saint Louis Missouri 63110 United States
  • University of Nebraska Medical Center
  • Omaha Nebraska 68198 United States
  • New York University Langone Medical Center - Perlmutter Cancer Center
  • New York New York 10016 United States
  • Weill Cornell Medical College
  • New York New York 10021 United States
  • Columbia University, Herbert Irving Comprehensive Cancer Center
  • New York New York 10032 United States
  • University of North Carolina School of Medicine
  • Chapel Hill North Carolina 27599 United States
  • University of Pittsburgh Medical Center
  • Pittsburgh Pennsylvania 15232 United States
  • Greenville Memorial Hospital
  • Greenville South Carolina 29615 United States
  • Inova Melanoma and Skin Cancer Center
  • Fairfax Virginia 22031 United States
  • Hospital de la Santa Creu i Sant Pau
  • Barcelona 08025 Spain
  • Hospital Clínic de Barcelona
  • Barcelona 08036 Spain
  • Catalan Institute of Oncology (ICO)
  • Barcelona 08908 Spain
  • Clinica Universidad de Navarra - Madrid location
  • Madrid 28027 Spain
  • Hospital Universitario 12 de Octubre
  • Madrid 28041 Spain
  • START Madrid - Centro Integral Oncológico Clara Campal (CIOCC)
  • Madrid 28050 Spain
  • Clinica Universidad de Navarra - Pamplona location
  • Pamplona 31008 Spain

View trial on ClinicalTrials.gov


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A Phase II Study of Dose-Dense Gemcitabine Plus Cisplatin (ddGC) in Patients With Muscle-Invasive Bladder Cancer With Bladder Preservation for Those Patients Whose Tumors Harbor Deleterious DNA Damage Response (DDR) Gene Alterations


Condition: Infiltrating Bladder Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma, Stage III Bladder Urothelial Carcinoma

Intervention:

  • Drug: Gemcitabine Hydrochloride
  • Drug: Cisplatin
  • Biological: Pegfilgrastim
  • Procedure: Conventional Surgery
  • Procedure: Radical Cystectomy
  • Other: Chemoradiotherapy

Purpose: This phase II trial studies how well gemcitabine hydrochloride and cisplatin work in treating participants with invasive bladder urothelial cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03609216

Sponsor: Alliance for Clinical Trials in Oncology

Primary Outcome Measures:

  • Measure: Proportion of patients who are recurrence-free within the DDR mutated group who undergo the bladder sparing approach
  • Time Frame: At 3 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Clinical response rate for patients harboring deleterious DDR gene alterations
  • Time Frame: After 6 courses (84 days)
  • Safety Issue:
  • Measure: Bladder-intact survival in DDR-altered patients with < cT1 responses who selected the bladder sparing approach
  • Time Frame: Time from registration up to 5 years
  • Safety Issue:
  • Measure: Overall survival
  • Time Frame: Time from study registration up to 5 years
  • Safety Issue:
  • Measure: Pathologic response (pT0) rate at cystectomy in participants without DDR gene alterations
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Recurrence-free survival
  • Time Frame: Time from study registration up to 5 years
  • Safety Issue:
  • Measure: The rate of cystectomies in patients with a DDR alteration and with a cT0/CIS/Ta response
  • Time Frame: Within 3 years
  • Safety Issue:
  • Measure: Proportion of patients in the bladder-sparing group who undergo local therapy
  • Time Frame: Up to 5 years
  • Safety Issue:

Estimated Enrollment: 271

Study Start Date: August 1, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Step 1 Patient Registration Eligibility Criteria
  • Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. 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 examination under anesthesia (EUA). The diagnostic TURBT sample must have been obtained within 60 days prior to registration
  • 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE) pre-treatment diagnostic transurethral resection (TUR) specimen available (for sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides. An FFPE block is also acceptable
  • Clinical stage T2-T4aN0/xM0 disease
  • Medically appropriate candidate for radical cystectomy as assessed by surgeon
  • No concomitant multifocal carcinoma in situ; a single focus is allowed
  • One focus of muscle-invasive bladder cancer and/or a tumor < 5 cm in size
  • No clinical or radiographic evidence for locally advanced or metastatic disease
  • No prior anti-PD-1, anti PD-L1 therapies, or systemic chemotherapy (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x 6 treatments; BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed)
  • No prior radiation therapy to the bladder
  • No major surgery or radiation therapy =< 4 weeks of registration
  • Not pregnant and not nursing. This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. For women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Calculated creatinine clearance >= 55 mL/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) * (For patients with documented Gilbert's syndrome bilirubin =< 3 x ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Alkaline phosphatase =< 2.5 x ULN
  • No hydronephrosis refractory to urinary diversion
  • No evidence of New York Heart Association (NYHA) functional class III or IV heart disease
  • No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade >= 2
  • No pre-existing sensory grade >= 2 neuropathy
  • No pre-existing grade >= 2 hearing loss
  • No serious intercurrent medical or psychiatric illness, including serious active infection
  • None 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
  • No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the drugs used in this trial. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy, when indicated
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to the agents used in this study
  • No concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (e.g., quality of life) are allowed
  • No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible
  • Step 2 Patient Registration Eligibility Criteria
  • Patients must have completed 4 or more cycles of protocol-directed chemotherapy
  • Step 3 Patient Registration

Eligibility Criteria:

  • Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. 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 examination under anesthesia (EUA). The diagnostic TURBT sample must have been obtained within 60 days prior to registration
  • 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE) pre-treatment diagnostic transurethral resection (TUR) specimen available (for sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides. An FFPE block is also acceptable
  • Clinical stage T2-T4aN0/xM0 disease
  • Medically appropriate candidate for radical cystectomy as assessed by surgeon
  • No concomitant multifocal carcinoma in situ; a single focus is allowed
  • One focus of muscle-invasive bladder cancer and/or a tumor < 5 cm in size
  • No clinical or radiographic evidence for locally advanced or metastatic disease
  • No prior anti-PD-1, anti PD-L1 therapies, or systemic chemotherapy (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x 6 treatments; BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed)
  • No prior radiation therapy to the bladder
  • No major surgery or radiation therapy =< 4 weeks of registration
  • Not pregnant and not nursing. This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. For women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Calculated creatinine clearance >= 55 mL/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) * (For patients with documented Gilbert's syndrome bilirubin =< 3 x ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Alkaline phosphatase =< 2.5 x ULN
  • No hydronephrosis refractory to urinary diversion
  • No evidence of New York Heart Association (NYHA) functional class III or IV heart disease
  • No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade >= 2
  • No pre-existing sensory grade >= 2 neuropathy
  • No pre-existing grade >= 2 hearing loss
  • No serious intercurrent medical or psychiatric illness, including serious active infection
  • None 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
  • No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the drugs used in this trial. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy, when indicated
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to the agents used in this study
  • No concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (e.g., quality of life) are allowed
  • No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible
  • Step 2 Patient Registration Eligibility Criteria
  • Patients must have completed 4 or more cycles of protocol-directed chemotherapy
  • Step 3 Patient Registration Eligibility Criteria (only patients with a DDR gene alteration)
  • Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the pre-treatment TURBT deoxyribonucleic acid (DNA)
  • Cystoscopy and imaging performed to determine stage/treatment assignment

Contact:

  • Gopa Iyer, MD
  • 646-888-4737

Locations:

  • CHI Saint Vincent Cancer Center Hot Springs
  • Hot Springs Arkansas 71913 United States
  • Fremont - Rideout Cancer Center
  • Marysville California 95901 United States
  • University of California Davis Comprehensive Cancer Center
  • Sacramento California 95817 United States
  • Penrose-Saint Francis Healthcare
  • Colorado Springs Colorado 80907 United States
  • Rocky Mountain Cancer Centers-Penrose
  • Colorado Springs Colorado 80907 United States
  • Porter Adventist Hospital
  • Denver Colorado 80210 United States
  • Mercy Medical Center
  • Durango Colorado 81301 United States
  • Southwest Oncology PC
  • Durango Colorado 81301 United States
  • Mountain Blue Cancer Care Center
  • Golden Colorado 80401 United States
  • Rocky Mountain Cancer Centers-Lakewood
  • Lakewood Colorado 80228 United States
  • Saint Anthony Hospital
  • Lakewood Colorado 80228 United States
  • Littleton Adventist Hospital
  • Littleton Colorado 80122 United States
  • Longmont United Hospital
  • Longmont Colorado 80501 United States
  • Rocky Mountain Cancer Centers-Longmont
  • Longmont Colorado 80501 United States
  • Parker Adventist Hospital
  • Parker Colorado 80138 United States
  • Rocky Mountain Cancer Centers-Parker
  • Parker Colorado 80138 United States
  • Saint Mary Corwin Medical Center
  • Pueblo Colorado 81004 United States
  • Rocky Mountain Cancer Centers - Pueblo
  • Pueblo Colorado 81008 United States
  • Rocky Mountain Cancer Centers-Thornton
  • Thornton Colorado 80260 United States
  • University of Florida Health Science Center - Gainesville
  • Gainesville Florida 32610 United States
  • Saint Alphonsus Cancer Care Center-Boise
  • Boise Idaho 83706 United States
  • Saint Alphonsus Cancer Care Center-Caldwell
  • Caldwell Idaho 83605 United States
  • Kootenai Medical Center
  • Coeur d'Alene Idaho 83814 United States
  • Walter Knox Memorial Hospital
  • Emmett Idaho 83617 United States
  • Idaho Urologic Institute-Meridian
  • Meridian Idaho 83642 United States
  • Saint Alphonsus Medical Center-Nampa
  • Nampa Idaho 83686 United States
  • Kootenai Cancer Center
  • Post Falls Idaho 83854 United States
  • Kootenai Cancer Clinic
  • Sandpoint Idaho 83864 United States
  • Illinois CancerCare-Bloomington
  • Bloomington Illinois 61704 United States
  • Illinois CancerCare-Canton
  • Canton Illinois 61520 United States
  • Memorial Hospital of Carbondale
  • Carbondale Illinois 62902 United States
  • SIH Cancer Institute
  • Carterville Illinois 62918 United States
  • Illinois CancerCare-Carthage
  • Carthage Illinois 62321 United States
  • Centralia Oncology Clinic
  • Centralia Illinois 62801 United States
  • Cancer Care Specialists of Illinois - Decatur
  • Decatur Illinois 62526 United States
  • Decatur Memorial Hospital
  • Decatur Illinois 62526 United States
  • Crossroads Cancer Center
  • Effingham Illinois 62401 United States
  • Illinois CancerCare-Eureka
  • Eureka Illinois 61530 United States
  • Illinois CancerCare-Galesburg
  • Galesburg Illinois 61401 United States
  • Western Illinois Cancer Treatment Center
  • Galesburg Illinois 61401 United States
  • Illinois CancerCare-Kewanee Clinic
  • Kewanee Illinois 61443 United States
  • Illinois CancerCare-Macomb
  • Macomb Illinois 61455 United States
  • Illinois CancerCare-Ottawa Clinic
  • Ottawa Illinois 61350 United States
  • Illinois CancerCare-Pekin
  • Pekin Illinois 61554 United States
  • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
  • Pekin Illinois 61554 United States
  • Illinois CancerCare-Peoria
  • Peoria Illinois 61615 United States
  • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
  • Peoria Illinois 61615 United States
  • Methodist Medical Center of Illinois
  • Peoria Illinois 61636 United States
  • OSF Saint Francis Medical Center
  • Peoria Illinois 61637 United States
  • Illinois CancerCare-Peru
  • Peru Illinois 61354 United States
  • Valley Radiation Oncology
  • Peru Illinois 61354 United States
  • Illinois CancerCare-Princeton
  • Princeton Illinois 61356 United States
  • Southern Illinois University School of Medicine
  • Springfield Illinois 62702 United States
  • Springfield Clinic
  • Springfield Illinois 62702 United States
  • Memorial Medical Center
  • Springfield Illinois 62781 United States
  • Cancer Care Specialists of Illinois-Swansea
  • Swansea Illinois 62226 United States
  • Southwest Illinois Health Services LLP
  • Swansea Illinois 62226 United States
  • Reid Health
  • Richmond Indiana 47374 United States
  • Medical Oncology and Hematology Associates-West Des Moines
  • Clive Iowa 50325 United States
  • Mercy Cancer Center-West Lakes
  • Clive Iowa 50325 United States
  • Alegent Health Mercy Hospital
  • Council Bluffs Iowa 51503 United States
  • Greater Regional Medical Center
  • Creston Iowa 50801 United States
  • Iowa Methodist Medical Center
  • Des Moines Iowa 50309 United States
  • Medical Oncology and Hematology Associates-Des Moines
  • Des Moines Iowa 50309 United States
  • Broadlawns Medical Center
  • Des Moines Iowa 50314 United States
  • Medical Oncology and Hematology Associates-Laurel
  • Des Moines Iowa 50314 United States
  • Mercy Medical Center - Des Moines
  • Des Moines Iowa 50314 United States
  • Iowa Lutheran Hospital
  • Des Moines Iowa 50316 United States
  • Trinity Regional Medical Center
  • Fort Dodge Iowa 50501 United States
  • Methodist West Hospital
  • West Des Moines Iowa 50266-7700 United States
  • Mercy Medical Center-West Lakes
  • West Des Moines Iowa 50266 United States
  • Flaget Memorial Hospital
  • Bardstown Kentucky 40004 United States
  • Commonwealth Cancer Center-Corbin
  • Corbin Kentucky 40701 United States
  • Saint Joseph Radiation Oncology Resource Center
  • Lexington Kentucky 40504 United States
  • Saint Joseph Hospital East
  • Lexington Kentucky 40509 United States
  • Saint Joseph London
  • London Kentucky 40741 United States
  • Jewish Hospital
  • Louisville Kentucky 40202 United States
  • Saints Mary and Elizabeth Hospital
  • Louisville Kentucky 40215 United States
  • Jewish Hospital Medical Center Northeast
  • Louisville Kentucky 40245 United States
  • Jewish Hospital Medical Center South
  • Shepherdsville Kentucky 40165 United States
  • East Jefferson General Hospital
  • Metairie Louisiana 70006 United States
  • Louisiana State University Health Science Center
  • New Orleans Louisiana 70112 United States
  • University Medical Center New Orleans
  • New Orleans Louisiana 70112 United States
  • Ochsner Medical Center Jefferson
  • New Orleans Louisiana 70121 United States
  • Mercy Medical Center
  • Springfield Massachusetts 01104 United States
  • Saint Joseph Mercy Hospital
  • Ann Arbor Michigan 48106 United States
  • IHA Hematology Oncology Consultants-Brighton
  • Brighton Michigan 48114 United States
  • Saint Joseph Mercy Brighton
  • Brighton Michigan 48114 United States
  • IHA Hematology Oncology Consultants-Canton
  • Canton Michigan 48188 United States
  • Saint Joseph Mercy Canton
  • Canton Michigan 48188 United States
  • Caro Cancer Center
  • Caro Michigan 48723 United States
  • IHA Hematology Oncology Consultants-Chelsea
  • Chelsea Michigan 48118 United States
  • Saint Joseph Mercy Chelsea
  • Chelsea Michigan 48118 United States
  • Hematology Oncology Consultants-Clarkston
  • Clarkston Michigan 48346 United States
  • Newland Medical Associates-Clarkston
  • Clarkston Michigan 48346 United States
  • Ascension Saint John Hospital
  • Detroit Michigan 48236 United States
  • Great Lakes Cancer Management Specialists-Doctors Park
  • East China Township Michigan 48054 United States
  • Genesee Cancer and Blood Disease Treatment Center
  • Flint Michigan 48503 United States
  • Genesee Hematology Oncology PC
  • Flint Michigan 48503 United States
  • Genesys Hurley Cancer Institute
  • Flint Michigan 48503 United States
  • Hurley Medical Center
  • Flint Michigan 48503 United States
  • Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
  • Grosse Pointe Woods Michigan 48236 United States
  • Lymphoma Clinic of Michigan
  • Grosse Pointe Woods Michigan 48236 United States
  • Michigan Breast Specialists-Grosse Pointe Woods
  • Grosse Pointe Woods Michigan 48236 United States
  • Sparrow Hospital
  • Lansing Michigan 48912 United States
  • Hope Cancer Clinic
  • Livonia Michigan 48154 United States
  • Saint Mary Mercy Hospital
  • Livonia Michigan 48154 United States
  • Great Lakes Cancer Management Specialists-Macomb Medical Campus
  • Macomb Michigan 48044 United States
  • Michigan Breast Specialists-Macomb Township
  • Macomb Michigan 48044 United States
  • Saint Mary's Oncology/Hematology Associates of Marlette
  • Marlette Michigan 48453 United States
  • 21st Century Oncology-Pontiac
  • Pontiac Michigan 48341 United States
  • Hope Cancer Center
  • Pontiac Michigan 48341 United States
  • Newland Medical Associates-Pontiac
  • Pontiac Michigan 48341 United States
  • Saint Joseph Mercy Oakland
  • Pontiac Michigan 48341 United States
  • Great Lakes Cancer Management Specialists-Rochester Hills
  • Rochester Hills Michigan 48309 United States
  • Saint Mary's of Michigan
  • Saginaw Michigan 48601 United States
  • Oncology Hematology Associates of Saginaw Valley PC
  • Saginaw Michigan 48604 United States
  • Bhadresh Nayak MD PC-Sterling Heights
  • Sterling Heights Michigan 48312 United States
  • Saint Joseph Health System-Tawas City
  • Tawas City Michigan 48764 United States
  • Advanced Breast Care Center PLLC
  • Warren Michigan 48088 United States
  • Great Lakes Cancer Management Specialists-Macomb Professional Building
  • Warren Michigan 48093 United States
  • Macomb Hematology Oncology PC
  • Warren Michigan 48093 United States
  • Michigan Breast Specialists-Warren
  • Warren Michigan 48093 United States
  • Saint John Macomb-Oakland Hospital
  • Warren Michigan 48093 United States
  • Saint Mary's Oncology/Hematology Associates of West Branch
  • West Branch Michigan 48661 United States
  • Huron Gastroenterology PC
  • Ypsilanti Michigan 48106 United States
  • IHA Hematology Oncology Consultants-Ann Arbor
  • Ypsilanti Michigan 48197 United States
  • Sanford Joe Lueken Cancer Center
  • Bemidji Minnesota 56601 United States
  • Essentia Health Saint Joseph's Medical Center
  • Brainerd Minnesota 56401 United States
  • Fairview Ridges Hospital
  • Burnsville Minnesota 55337 United States
  • Mercy Hospital
  • Coon Rapids Minnesota 55433 United States
  • Essentia Health - Deer River Clinic
  • Deer River Minnesota 56636 United States
  • Essentia Health Saint Mary's - Detroit Lakes Clinic
  • Detroit Lakes Minnesota 56501 United States
  • Essentia Health Cancer Center
  • Duluth Minnesota 55805 United States
  • Essentia Health Saint Mary's Medical Center
  • Duluth Minnesota 55805 United States
  • Miller-Dwan Hospital
  • Duluth Minnesota 55805 United States
  • Fairview-Southdale Hospital
  • Edina Minnesota 55435 United States
  • Lake Region Healthcare Corporation-Cancer Care
  • Fergus Falls Minnesota 56537 United States
  • Essentia Health - Fosston
  • Fosston Minnesota 56542 United States
  • Unity Hospital
  • Fridley Minnesota 55432 United States
  • Essentia Health Hibbing Clinic
  • Hibbing Minnesota 55746 United States
  • Fairview Maple Grove Medical Center
  • Maple Grove Minnesota 55369 United States
  • Minnesota Oncology Hematology PA-Maplewood
  • Maplewood Minnesota 55109 United States
  • Saint John's Hospital - Healtheast
  • Maplewood Minnesota 55109 United States
  • Abbott-Northwestern Hospital
  • Minneapolis Minnesota 55407 United States
  • Hennepin County Medical Center
  • Minneapolis Minnesota 55415 United States
  • Health Partners Inc
  • Minneapolis Minnesota 55454 United States
  • Monticello Cancer Center
  • Monticello Minnesota 55362 United States
  • New Ulm Medical Center
  • New Ulm Minnesota 56073 United States
  • Essentia Health - Park Rapids
  • Park Rapids Minnesota 56470 United States
  • North Memorial Medical Health Center
  • Robbinsdale Minnesota 55422 United States
  • Park Nicollet Clinic - Saint Louis Park
  • Saint Louis Park Minnesota 55416 United States
  • Regions Hospital
  • Saint Paul Minnesota 55101 United States
  • United Hospital
  • Saint Paul Minnesota 55102 United States
  • Essentia Health Sandstone
  • Sandstone Minnesota 55072 United States
  • Saint Francis Regional Medical Center
  • Shakopee Minnesota 55379 United States
  • Lakeview Hospital
  • Stillwater Minnesota 55082 United States
  • Sanford Thief River Falls Medical Center
  • Thief River Falls Minnesota 56701 United States
  • Essentia Health Virginia Clinic
  • Virginia Minnesota 55792 United States
  • Ridgeview Medical Center
  • Waconia Minnesota 55387 United States
  • Rice Memorial Hospital
  • Willmar Minnesota 56201 United States
  • Minnesota Oncology Hematology PA-Woodbury
  • Woodbury Minnesota 55125 United States
  • Sanford Cancer Center Worthington
  • Worthington Minnesota 56187 United States
  • Fairview Lakes Medical Center
  • Wyoming Minnesota 55092 United States
  • Parkland Health Center-Bonne Terre
  • Bonne Terre Missouri 63628 United States
  • Saint Francis Medical Center
  • Cape Girardeau Missouri 63703 United States
  • Southeast Cancer Center
  • Cape Girardeau Missouri 63703 United States
  • Siteman Cancer Center at West County Hospital
  • Creve Coeur Missouri 63141 United States
  • Capital Region Southwest Campus
  • Jefferson City Missouri 65109 United States
  • Washington University School of Medicine
  • Saint Louis Missouri 63110 United States
  • Siteman Cancer Center-South County
  • Saint Louis Missouri 63129 United States
  • Missouri Baptist Medical Center
  • Saint Louis Missouri 63131 United States
  • Sainte Genevieve County Memorial Hospital
  • Sainte Genevieve Missouri 63670 United States
  • Missouri Baptist Sullivan Hospital
  • Sullivan Missouri 63080 United States
  • Missouri Baptist Outpatient Center-Sunset Hills
  • Sunset Hills Missouri 63127 United States
  • Community Hospital of Anaconda
  • Anaconda Montana 59711 United States
  • Billings Clinic Cancer Center
  • Billings Montana 59101 United States
  • Bozeman Deaconess Hospital
  • Bozeman Montana 59715 United States
  • Benefis Healthcare- Sletten Cancer Institute
  • Great Falls Montana 59405 United States
  • Great Falls Clinic
  • Great Falls Montana 59405 United States
  • Saint Peter's Community Hospital
  • Helena Montana 59601 United States
  • Kalispell Regional Medical Center
  • Kalispell Montana 59901 United States
  • Community Medical Hospital
  • Missoula Montana 59804 United States
  • CHI Health Saint Francis
  • Grand Island Nebraska 68803 United States
  • Heartland Hematology and Oncology
  • Kearney Nebraska 68845 United States
  • CHI Health Good Samaritan
  • Kearney Nebraska 68847 United States
  • Saint Elizabeth Regional Medical Center
  • Lincoln Nebraska 68510 United States
  • Alegent Health Immanuel Medical Center
  • Omaha Nebraska 68122 United States
  • Hematology and Oncology Consultants PC
  • Omaha Nebraska 68122 United States
  • Alegent Health Bergan Mercy Medical Center
  • Omaha Nebraska 68124 United States
  • Alegent Health Lakeside Hospital
  • Omaha Nebraska 68130 United States
  • Creighton University Medical Center
  • Omaha Nebraska 68131 United States
  • Midlands Community Hospital
  • Papillion Nebraska 68046 United States
  • Memorial Sloan Kettering Basking Ridge
  • Basking Ridge New Jersey 07920 United States
  • Englewood Hospital and Medical Center
  • Englewood New Jersey 07631 United States
  • Memorial Sloan Kettering Monmouth
  • Middletown New Jersey 07748 United States
  • Memorial Sloan Kettering Bergen
  • Montvale New Jersey 07645 United States
  • Roswell Park Cancer Institute
  • Buffalo New York 14263 United States
  • Memorial Sloan Kettering Commack
  • Commack New York 11725 United States
  • Memorial Sloan Kettering Westchester
  • Harrison New York 10604 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States
  • Memorial Sloan Kettering Rockville Centre
  • Rockville Centre New York 11570 United States
  • State University of New York Upstate Medical University
  • Syracuse New York 13210 United States
  • Southeastern Medical Oncology Center-Clinton
  • Clinton North Carolina 28328 United States
  • Southeastern Medical Oncology Center-Goldsboro
  • Goldsboro North Carolina 27534 United States
  • Wayne Memorial Hospital
  • Goldsboro North Carolina 27534 United States
  • Onslow Memorial Hospital
  • Jacksonville North Carolina 28546 United States
  • Southeastern Medical Oncology Center-Jacksonville
  • Jacksonville North Carolina 28546 United States
  • Sanford Bismarck Medical Center
  • Bismarck North Dakota 58501 United States
  • Essentia Health Cancer Center-South University Clinic
  • Fargo North Dakota 58103 United States
  • Sanford South University Medical Center
  • Fargo North Dakota 58103 United States
  • Sanford Medical Center Fargo
  • Fargo North Dakota 58104 United States
  • Roger Maris Cancer Center
  • Fargo North Dakota 58122 United States
  • Sanford Broadway Medical Center
  • Fargo North Dakota 58122 United States
  • Essentia Health - Jamestown Clinic
  • Jamestown North Dakota 58401 United States
  • Indu and Raj Soin Medical Center
  • Beavercreek Ohio 45431 United States
  • Dayton Physicians LLC-Miami Valley South
  • Centerville Ohio 45459 United States
  • Miami Valley Hospital South
  • Centerville Ohio 45459 United States
  • Good Samaritan Hospital - Cincinnati
  • Cincinnati Ohio 45220 United States
  • Oncology Hematology Care Inc-Kenwood
  • Cincinnati Ohio 45236 United States
  • Bethesda North Hospital
  • Cincinnati Ohio 45242 United States
  • TriHealth Cancer Institute-Westside
  • Cincinnati Ohio 45247 United States
  • TriHealth Cancer Institute-Anderson
  • Cincinnati Ohio 45255 United States
  • Good Samaritan Hospital - Dayton
  • Dayton Ohio 45406 United States
  • Miami Valley Hospital
  • Dayton Ohio 45409 United States
  • Dayton Physician LLC-Miami Valley Hospital North
  • Dayton Ohio 45415 United States
  • Miami Valley Hospital North
  • Dayton Ohio 45415 United States
  • Armes Family Cancer Center
  • Findlay Ohio 45840 United States
  • Blanchard Valley Hospital
  • Findlay Ohio 45840 United States
  • Orion Cancer Care
  • Findlay Ohio 45840 United States
  • Atrium Medical Center-Middletown Regional Hospital
  • Franklin Ohio 45005-1066 United States
  • Dayton Physicians LLC-Atrium
  • Franklin Ohio 45005 United States
  • Dayton Physicians LLC-Wayne
  • Greenville Ohio 45331 United States
  • Wayne Hospital
  • Greenville Ohio 45331 United States
  • Greater Dayton Cancer Center
  • Kettering Ohio 45409 United States
  • First Dayton Cancer Care
  • Kettering Ohio 45420 United States
  • Kettering Medical Center
  • Kettering Ohio 45429 United States
  • Springfield Regional Cancer Center
  • Springfield Ohio 45504 United States
  • Springfield Regional Medical Center
  • Springfield Ohio 45505 United States
  • Dayton Physicians LLC-Upper Valley
  • Troy Ohio 45373 United States
  • Upper Valley Medical Center
  • Troy Ohio 45373 United States
  • University of Oklahoma Health Sciences Center
  • Oklahoma City Oklahoma 73104 United States
  • Oklahoma Cancer Specialists and Research Institute-Tulsa
  • Tulsa Oklahoma 74146 United States
  • Saint Alphonsus Medical Center-Baker City
  • Baker City Oregon 97814 United States
  • Saint Alphonsus Medical Center-Ontario
  • Ontario Oregon 97914 United States
  • Lehigh Valley Hospital-Cedar Crest
  • Allentown Pennsylvania 18103 United States
  • Lehigh Valley Hospital - Muhlenberg
  • Bethlehem Pennsylvania 18017 United States
  • Pocono Medical Center
  • East Stroudsburg Pennsylvania 18301 United States
  • Lehigh Valley Hospital-Hazleton
  • Hazleton Pennsylvania 18201 United States
  • Greenville Health System Cancer Institute-Laurens
  • Clinton South Carolina 29325 United States
  • Greenville Health System Cancer Institute-Easley
  • Easley South Carolina 29640 United States
  • Greenville Health System Cancer Institute-Butternut
  • Greenville South Carolina 29605 United States
  • Greenville Health System Cancer Institute-Faris
  • Greenville South Carolina 29605 United States
  • Greenville Memorial Hospital
  • Greenville South Carolina 29605 United States
  • Greenville Health System Cancer Institute-Eastside
  • Greenville South Carolina 29615 United States
  • Greenville Health System Cancer Institute-Greer
  • Greer South Carolina 29650 United States
  • Greenville Health System Cancer Institute-Seneca
  • Seneca South Carolina 29672 United States
  • Greenville Health System Cancer Institute-Spartanburg
  • Spartanburg South Carolina 29307 United States
  • Sanford Cancer Center Oncology Clinic
  • Sioux Falls South Dakota 57104 United States
  • Sanford USD Medical Center - Sioux Falls
  • Sioux Falls South Dakota 57117-5134 United States
  • Memorial Hospital
  • Chattanooga Tennessee 37404 United States
  • Pulmonary Medicine Center of Chattanooga-Hixson
  • Hixson Tennessee 37343 United States
  • Memorial GYN Plus
  • Ooltewah Tennessee 37363 United States
  • Saint Joseph Regional Cancer Center
  • Bryan Texas 77802 United States
  • Harrison HealthPartners Hematology and Oncology-Bremerton
  • Bremerton Washington 98310 United States
  • Harrison Medical Center
  • Bremerton Washington 98310 United States
  • Highline Medical Center-Main Campus
  • Burien Washington 98166 United States
  • Saint Elizabeth Hospital
  • Enumclaw Washington 98022 United States
  • Saint Francis Hospital
  • Federal Way Washington 98003 United States
  • Saint Clare Hospital
  • Lakewood Washington 98499 United States
  • Harrison HealthPartners Hematology and Oncology-Poulsbo
  • Poulsbo Washington 98370 United States
  • Franciscan Research Center-Northwest Medical Plaza
  • Tacoma Washington 98405 United States
  • Northwest Medical Specialties PLLC
  • Tacoma Washington 98405 United States
  • United Hospital Center
  • Bridgeport West Virginia 26330 United States
  • WVUH-Berkely Medical Center
  • Martinsburg West Virginia 25401 United States
  • West Virginia University Healthcare
  • Morgantown West Virginia 26506 United States
  • Camden Clark Medical Center
  • Parkersburg West Virginia 26101 United States
  • Duluth Clinic Ashland
  • Ashland Wisconsin 54806 United States
  • Northwest Wisconsin Cancer Center
  • Ashland Wisconsin 54806 United States
  • Marshfield Clinic Cancer Center - Eau Claire
  • Eau Claire Wisconsin 54701 United States
  • Cancer Center of Western Wisconsin
  • New Richmond Wisconsin 54017 United States
  • Billings Clinic-Cody
  • Cody Wyoming 82414 United States
  • Welch Cancer Center
  • Sheridan Wyoming 82801 United States

View trial on ClinicalTrials.gov


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A Multicenter Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of the Combination of Rogaratinib and Copanlisib in Patients With FGFR-positive, Locally Advanced or Metastatic Solid Tumors


Condition: Advanced or Metastatic Solid Tumor

Intervention:

  • Drug: Rogaratinib (BAY1163877)
  • Drug: Copanlisib (BAY80-6946)

Purpose: The primary objective of this study is to determine the safety, tolerability, maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) and efficacy of rogaratinib in combination with copanlisib in patients with locally advanced or metastatic solid tumors that are mRNA-positive for at least one FGFR1-4 subtype. The secondary objectives of this study are to characterize the pharmacokinetics (PK) of rogaratinib and copanlisib alone and in combination, and to assess the anti-tumor efficacy of rogaratinib in combination with copanlisib locally advanced or metastatic solid tumors that are mRNA-positive for at least one FGFR1-4 subtype.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03517956

Sponsor: Bayer

Primary Outcome Measures:

  • Measure: Incidence of treatment-emergent adverse events (TEAEs)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Incidence of drug-related TEAEs
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Incidence of treatment-emergent serious adverse events (TESAEs)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Incidence of Dose-limiting toxicities (DLTs)
  • Time Frame: Approximately 10 months
  • Safety Issue:
  • Measure: Objective response rate (ORR) at recommended dose
  • Time Frame: Up to 22 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Maximum plasma concentration of Copanlisib (Cmax)
  • Time Frame: 0 (pre-dose), 0.5, 1 (end of infusion), 2, 4, 8, 24, 48 hours after drug administration (Days 1, 2, 3) and 0, 0.5, 1, 2, 4, 8, 24, 48 hours after drug administration (Days 15, 16, 17) in dose escalation
  • Safety Issue:
  • Measure: Area under the plasma concentration versus time curve of Copanlisib (AUC (0-48))
  • Time Frame: 0 (pre-dose), 0.5, 1 (end of infusion), 2, 4, 8, 24, 48 hours after drug administration (Days 1, 2, 3) and 0, 0.5, 1, 2, 4, 8, 24, 48 hours after drug administration (Days 15, 16, 17) in dose escalation
  • Safety Issue:
  • Measure: Area under the plasma concentration versus time curve of Rogaratinib (AUC (0-8))
  • Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8 hours after drug (Day 14) and 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 24, 48 hours after drug (Days 15 to 17) in dose escalation; 0 (pre-dose) and 1 hour after drug on Day 1 of dose expansion
  • Safety Issue:
  • Measure: Maximum plasma concentration of Rogaratinib (Cmax)
  • Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8 hours after drug (Day 14) and 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 24, 48 hours after drug (Days 15 to 17) in dose escalation; 0 (pre-dose) and 1 hour after drug on Day 1 of dose expansion
  • Safety Issue:
  • Measure: Objective response rate (ORR)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Disease control rate (DCR)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Duration of response (DOR) for Partial Response and Complete Response
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Progression-free survival (PFS)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Overall survival (OS)
  • Time Frame: Up to 32 months
  • Safety Issue:

Estimated Enrollment: 65

Study Start Date: July 25, 2018

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • High FGFR mRNA expression levels (RNAscope score of ≥3; measurement is part of this protocol) in archival or fresh tumor biopsy specimen.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
  • At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in contrast enhanced (unless contraindicated) CT or MRI.
  • Adequate bone marrow, liver and renal function.
  • Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) formula.
  • Left ventricular ejection fraction (LVEF) equal to or above the lower limit of normal (LLN) at the institution.
  • Life expectancy of at least 3 months.
  • For the dose escalation part: Patients with histologically confirmed, locally advanced or metastatic solid tumors who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anti-cancer treatment is no longer effective, excluding primary brain or spinal tumors. Patients who have been advised with all standard treatment options and still refuse them must be documented and can be allowed to enter the trial.
  • For the dose expansion part: Patients with histologically confirmed, locally advanced or metastatic urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anticancer treatment is no longer effective. Patients who have been advised with all standard treatment options and still refuse them must be documented and can be allowed to enter the trial.

Exclusion Criteria:

  • Previous or concurrent cancer that is distinct from tumor for which the patient is enrolled in study, with exceptions
  • Ongoing or previous anti-cancer treatment within 4 weeks of study treatment start (or 6 weeks for mitomycin C, nitrosoureas and monoclonal antibodies); with exceptions.
  • Prior toxicity to anti-FGFR-directed or anti-PI3K-directed therapies leading to treatment discontinuation (previous exposure is allowed in other circumstances). If prior toxicity to anti-FGFR-directed or anti-PI3K-directed therapies leading to treatment discontinuation is different from the known safety profile of rogaratinib or copanlisib, enrollment is allowed.
  • Symptomatic brain or meningeal metastatic tumors unless the patient is >6 months from definitive therapy, has no evidence of tumor growth on an imaging study and is clinically stable with respect to the tumor at the start of study treatment. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies).
  • History or current condition of an uncontrolled cardiovascular disease including congestive heart failure NYHA > Class 2, unstable angina (symptoms of angina at rest) or new-onset angina (within last 3 months) or myocardial infarction within past 6 months and cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted).
  • Active hepatitis B (HBV) or C (HCV) infection.
  • Active clinically serious infections (≥ CTCAE v4.03 Grade 2).

Contact:

  • Bayer Clinical Trials Contact
  • (+)1-888-84 22937

Locations:

  • USC Norris Hospital and Clinics
  • Los Angeles California 90033 United States
  • Northwestern University
  • Chicago Illinois 60611 United States
  • University of Maryland
  • Baltimore Maryland 12101 United States
  • Dana-Farber Cancer Institute
  • Boston Massachusetts 02215 United States
  • Barbara Ann Karmanos Cancer Institute
  • Detroit Michigan 48201 United States
  • Comprehensive Cancer Centers of Nevada
  • Las Vegas Nevada 89169 United States
  • Memorial Sloan-Kettering Cancer Center
  • New York New York 10065 United States
  • Greenville Health System
  • Greenville South Carolina 29605 United States
  • Texas Oncology- Austin Midtown
  • Austin Texas 78705 United States
  • Tyler Cancer Center
  • Tyler Texas 75702 United States
  • CU Saint-Luc/UZ St-Luc
  • Bruxelles - Brussel 1200 Belgium
  • UZ Antwerpen
  • Edegem 2650 Belgium
  • CHU de Liège
  • Liege 4000 Belgium
  • Centre Oscar Lambret - Lille
  • LILLE cedex 59020 France
  • Centre Léon Bérard
  • Lyon Cedex 69008 France
  • Krankenhaus Nordwest
  • Frankfurt Hessen 60488 Germany
  • Universitätsklinikum Köln
  • Köln Nordrhein-Westfalen 50937 Germany
  • Universitätsklinikum Hamburg Eppendorf (UKE)
  • Hamburg 20246 Germany
  • Klinikum der Universität Würzburg
  • Würzburg 97080 Germany
  • Asan Medical Center
  • Seoul 05505 Korea, Republic of
  • Samsung Medical Center
  • Seoul 06351 Korea, Republic of
  • Yonsei University College of Medicine
  • Seoul 120-752 Korea, Republic of
  • National University Hospital
  • Singapore 119074 Singapore
  • National Cancer Center
  • Singapore 169610 Singapore
  • Ciutat Sanitària i Universitaria de la Vall d'Hebron
  • Barcelona 08035 Spain
  • Hospital Clínic i Provincial de Barcelona
  • Barcelona 08036 Spain
  • Hospital General Universitario Gregorio Marañón
  • Madrid 28007 Spain
  • MD Anderson International Espanya, S.A.
  • Madrid 28033 Spain
  • Hospital Clínico Universitario de Valencia
  • Valencia 46010 Spain

View trial on ClinicalTrials.gov


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A Phase 2 Study of Sitravatinib in Combination With Nivolumab in Patients With Advanced or Metastatic Urothelial Carcinoma


Condition: Urothelial Carcinoma, Urothelial Carcinoma Bladder, Urothelial Carcinoma Ureter, Urothelial Carcinoma of the Renal Pelvis and Ureter, Urothelial Carcinoma Urethra

Intervention:

  • Drug: Sitravatinib
  • Drug: Nivolumab

Purpose: The study will evaluate the clinical activity of nivolumab in combination with the investigational agent sitravatinib in patients with advanced or metastatic urothelial carcinoma.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03606174

Sponsor: Mirati Therapeutics Inc.

Primary Outcome Measures:

  • Measure: Number of patients experiencing tumor size reduction
  • Time Frame: up to 3 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Number of patients experiencing adverse events
  • Time Frame: up to 12 months
  • Safety Issue:
  • Measure: Blood plasma concentration of the investigational agent
  • Time Frame: up to 20 weeks
  • Safety Issue:

Estimated Enrollment: 80

Study Start Date: September 11, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Diagnosis of urothelial carcinoma
  • Most recent treatment must have included a checkpoint inhibitor
  • Adequate bone marrow and organ function

Exclusion Criteria:

  • Uncontrolled tumor in the brain
  • Unacceptable toxicity with prior checkpoint inhibitor
  • Impaired heart function

Contact:

  • Mirati Therapeutics Study Locator Services
  • 1-844-893-5530 (toll free)

Locations:

  • Rocky Mountain Cancer Centers-Aurora
  • Aurora Colorado 80012 United States
  • SCRI - Florida Cancer Specialists- North Region
  • Saint Petersburg Florida 33705 United States
  • Florida Cancer Specialist-West Palm Beach
  • West Palm Beach Florida 33401 United States
  • The University of Chicago
  • Chicago Illinois 60637 United States
  • Karmanos Cancer Institute
  • Detroit Michigan 48201 United States
  • Washington University in St Louis
  • Saint Louis Missouri 63110 United States
  • GU Research Network/Urology Cancer Center
  • Omaha Nebraska 68130 United States
  • Comprehensive Cancer Centers of Nevada
  • Las Vegas Nevada 89169 United States
  • New York Oncology Hematology
  • Albany New York 12206 United States
  • Northwell Cancer Institute
  • Lake Success New York 11042 United States
  • The Ohio State University
  • Columbus Ohio 43202 United States
  • Allegheny Singer Research Institute
  • Pittsburgh Pennsylvania 15212 United States
  • Texas Oncology-Austin Central
  • Austin Texas 78731 United States
  • Texas Oncology- Memorial City
  • Houston Texas 77024 United States
  • MD Anderson Cancer Center
  • Houston Texas 77030 United States
  • Texas Oncology - Tyler
  • Tyler Texas 75702 United States
  • Virginia Cancer Specialists- Fairfax
  • Fairfax Virginia 22031 United States

View trial on ClinicalTrials.gov


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A Phase I/II Study of IMCnyeso, HLA- A*0201-Restricted, NY-ESO-1- and LAGE-1A-specific Soluble T Cell Receptor and Anti-CD3 Bispecific Molecule, in HLA-A*0201 Positive Patients With Advanced NY-ESO-1 and/or LAGE - 1A Positive Cancer


Condition: Melanoma, Advanced NSCLC, Urothelial Carcinoma, Synovial Sarcoma

Intervention:

  • Drug: IMCnyeso
  • Drug: IMCnyeso

Purpose: IMCnyeso is a new biological therapy designed for the treatment of cancers which express NY-ESO-1 and/or LAGE-1A. This is a first-in-human trial designed to evaluate the safety and efficacy of IMCnyeso in adult patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for NY-ESO-1 and/or LAGE-A1.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03515551

Sponsor: Immunocore Ltd

Primary Outcome Measures:

  • Measure: Recommended phase 2 dose (RP2D)
  • Time Frame: From day 1 to day 28 of treatment
  • Safety Issue:
  • Measure: Number of patients with treatment emergent AEs
  • Time Frame: Safety will be assessed from informed consent through 90 days after end of treatment
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Objective response rate (ORR) defined as the proportion of patients achieving an objective response (RECIST v1.1 and modified irRECIST) (Arm 2 only)
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Disease control rate (DCR) defined as the proportion of patients with either an objective response or stable disease (RECIST v1.1 and modified irRECIST). (Part 2 only)
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Pharmacokinetics
  • Time Frame: 2 weeks (AUC will be assessed weekly for 2 weeks)
  • Safety Issue:
  • Measure: Pharmacokinetics
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Pharmacokinetics
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Pharmacokinetics
  • Time Frame: 2 weeks (t1/2 will be assessed after the first two doses of IMCnyeso, an average of 2 weeks)
  • Safety Issue:
  • Measure: Pharmacokinetics
  • Time Frame: up to 2 years
  • Safety Issue:

Estimated Enrollment: 63

Study Start Date: May 1, 2018

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  1. Male or female patients age ≥ 18 years of age at the time of informed consent
  2. HLA-A*0201 positive, confirmed by central laboratory
  3. NY-ESO-1 and/or LAGE-1A positive tumor confirmed by the central laboratory
  4. Arm 1: Patients must be refractory to or intolerant to all existing therapies known to provide clinical benefit for their condition.
  5. Arm 2: Subjects will have received the following previous therapies:
  6. NSCLC — PD-1/PD-L1 inhibitor
  7. Patients with NSCLC and an EGFR or ALK genomic tumor aberration must have disease progression after treatment with Health Authority-approved agents for these aberrations
  8. Urothelial cancer — PD-1/PD-L1 inhibitor
  9. Synovial sarcoma — at least one prior chemotherapy regimen
  10. Arm 1 only: Histologically confirmed diagnosis of advanced NSCLC, melanoma, urothelial carcinoma, or synovial sarcoma
  11. Arm 2 only: Histologically confirmed diagnosis of advanced NSCLC, urothelial carcinoma, or synovial sarcoma
  12. Arm 2 only: Disease amenable to biopsy
  13. Arm 2 only: Measurable disease to RECIST v.1.1 criteria

Exclusion Criteria:

  1. Impaired baseline organ function as evaluated by out-of-range laboratory values
  2. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies
  3. Clinically significant cardiac disease or impaired cardiac function
  4. Presence of symptomatic or untreated central nervous system (CNS) metastases
  5. Active infection requiring systemic antibiotic therapy
  6. Known history of human immunodeficiency virus infection (HIV)
  7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  8. Malignant disease, other than that being treated in this study
  9. Patients receiving systemic steroid therapy or any other systemic immunosuppressive medication. Local steroid therapies are acceptable
  10. Systemic anti-cancer therapy within 2 weeks of the first dose of study drug.
  11. Major surgery within 2 weeks of the first dose of study drug
  12. Radiotherapy within 2 weeks of the first dose of study drug, with the exception of palliative radiotherapy to a limited field
  13. Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GM-CSF, M-CSF) ≤ 2 weeks prior to start of study drug
  14. Pregnant, likely to become pregnant, or lactating women

Contact:

  • Shannon Marshall
  • 484-534-5261

Locations:

  • Washington University School of Medicine in St. Louis
  • Saint Louis Missouri 63110 United States
  • Thomas Jefferson University Hospital
  • Philadelphia Pennsylvania 19107 United States
  • Hillman Cancer Center
  • Pittsburgh Pennsylvania 15232 United States
  • MD Anderson Cancer Center
  • Houston Texas 77030 United States
  • The Christie Hospital
  • Manchester United Kingdom
  • Royal Marsden
  • Sutton United Kingdom

View trial on ClinicalTrials.gov


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Avelumab as Neoadjuvant Therapy in Subjects With Urothelial Muscle Invasive Bladder Cancers


Condition: Non-metastatic Muscle Invasive Bladder Cancer

Intervention:

  • Drug: Avelumab
  • Procedure: cystectomy
  • Combination Product: CG
  • Combination Product: DD-MVAC
  • Combination Product: PG

Purpose: Open-label, interventional, multi-centre, randomized phase II study. Cancer studied is non-metastatic muscle invasive bladder cancer (MIBC). Avelumab administered every 2 weeks is used as neoadjuvant therapy in subjects with urothelial muscle invasive bladder cancers in combination with standard chemotherapy or alone.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03674424

Sponsor: Jules Bordet Institute

Primary Outcome Measures:

  • Measure: To determine the pathologic complete response (ypT0/Tis ypN0) following neoadjuvant treatment in patients with non-metastatic MIBC.
  • Time Frame: during surgery
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: To determine the pathologic response rate (
  • Time Frame: during surgery
  • Safety Issue:
  • Measure: Assessment of the toxicity profile of regimen using the adverse events reported: NCI CTCAE v4.03
  • Time Frame: through study completion, an average of 3 months
  • Safety Issue:

Estimated Enrollment: 166

Study Start Date: June 1, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • 1. Age ≥ 18 years old 2. Must have histologically confirmed muscle invasive urothelial carcinoma (transitional cell carcinoma) or urothelial carcinoma with mixed histology of the bladder, renal pelvis or ureters. Stage permitted: T2, T3 or T4a. T stage is based on the standard of care transurethral resection of the bladder tumour (TURBT) sample 3. Patients may have nodal disease (Nx, N0, N1 or N2) at imagery but there must be no evidence of distant metastases (M0) 4. Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG). 5. Be a medically appropriate candidate for surgery as determined by an attending urologist 6. Adequate bone marrow function as defined below:
  • Absolute neutrophil count ≥1500/µL or 1.5x109/L
  • Hemoglobin ≥ 9 g/dL
  • Platelets ≥100000/µL or 100x109/L 7) 7. Adequate liver function as defined below:
  • Serum total bilirubin ≤ 1.5 x ULN. In case of known Gilbert's syndrome < 3xUNL is allowed
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN 8. Serum pregnancy test (for subjects of childbearing potential) negative within 7 days prior to study treatment administration. 9. Women of childbearing potential must agree to use one highly effective method of contraception prior study entry, during the course of the study and up to 6 months after the last administration of study treatment. Men with childbearing potential partner must agree to use condom during the course of this study and up to 6 months after the last administration of the study treatment. 10. Completion of all necessary screening procedures within 28 days prior to treatment. 11. Availability of biological material for screening and/or translational research activities 12. Signed Informed Consent form (ICF) obtained prior to any study related procedure. Cisplatin-eligible cohort specific criteria: 13. Glomerular filtration rate (GFR) or Creatinine Clearance≥ 60 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) and 14. Peripheral neuropathy ≤ grade 1 and 15. Hearing impaired ≤ grade 1 and 16. Adequate cardiac function (Left Ventricular Ejection Fraction LVEF ≥ 55%) by MUGA (Multiple-Gated Acquisition) scan or echocardiography Cisplatin ineligible cohort specific criteria (if any of the following criteria): 17. Glomerular filtration rate (GFR) or Creatinine Clearance ≥ 30mL/min according to the Cockcroft-Gault formula (or local institutional standard method) or 18. Peripheral neuropathy ≥ grade 2 or 19. Hearing impaired ≥ grade 2 Inclusion criterion specific for France: 20. Patients must be affiliated to a social security system

Exclusion Criteria:

  1. Subjects meeting one of the following criteria are not eligible for this study:
  2. Metastatic disease (M1)
  3. Has had prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy for urothelial carcinoma
  4. Prior treatment with drug specifically targeting T-cell co-stimulation or checkpoint pathways
  5. Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  6. Has an active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
  7. Has had a prior organ transplantation including allogenic stem-cell transplantation.
  8. Has an active infection requiring systemic therapy
  9. Has a known history of Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency syndrome.
  10. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA is detected)
  11. Has received vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines such as influenza vaccine.
  12. 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
  13. History of prior invasive malignancy within 2 years (exception of adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localised prostate cancer or ductal carcinoma in situ)
  14. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
  15. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication."
  16. Pregnant and/or lactating women.
  17. Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.
  18. Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade >1); however, alopecia, sensory neuropathy Grade ≤2, or other Grade ≤2 not constituting a safety risk based on investigator's judgment are acceptable.
  19. Other severe acute chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with the study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. Exclusion criterion specific for France:
  20. Vulnerable persons according to the article L.1121-6 of the CSP, adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the CSP.

Locations:

  • Centre Hospitalier Universitaire et Psychiatrique de Mons-Borinage
  • Mons Hainaut 7000 Belgium
  • Institut Jules Bordet
  • Brussels 1000 Belgium
  • CHU de Liège Sart Tilman
  • Liège 4000 Belgium
  • CHU Namur - Sainte Elisabeth
  • Namur 5000 Belgium

View trial on ClinicalTrials.gov


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A Multicenter Randomized Double Blind Study Examining the Efficacy and Safety of Denosumab in Combination With First Line Platinum-based Chemotherapy for Patients With Bone Metastasis Secondary to Metastatic Urothelial Cancer


Condition: Urothelial Carcinoma, Kidney Cancer, Ureter Cancer, Bladder Cancer

Intervention:

  • Drug: Denosumab
  • Other: Denosumab Placebo
  • Drug: Gemcitabine
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Dietary Supplement: Calcium
  • Dietary Supplement: Vitamin D

Purpose: This is a phase 2 study of the drug denosumab for the management bone metastases from urothelial cancer. The purpose of this study is to find out how effective denosumab is in the management of bone metastases from urothelial cancer. This will be done by comparing denosumab with standard treatment, compared to placebo and standard treatment. Denosumab is a monoclonal antibody that binds to a protein called Receptor Activator of Nuclear Factor κB (RANK). RANK works by telling certain cells called osteoclasts to break down bone tissue. The binding of denosumab to RANK stops it from telling osteoclasts to break down bone tissue which may help with symptoms related bone metastases from urothelial cancer.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03520231

Sponsor: University Health Network, Toronto

Primary Outcome Measures:

  • Measure: Difference in mean percentage change in serum c-telopeptide (sCTX) between the two arms (investigational drug arm and placebo arm).
  • Time Frame: Baseline to Week 10
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Number of patients with a change in sCTx
  • Time Frame: Baseline to Week 10
  • Safety Issue:
  • Measure: Mean percentage change in serum bone-specific alkaline phosphatase (bALP) in the investigational arm
  • Time Frame: Baseline to Week 10
  • Safety Issue:
  • Measure: Mean percentage change in urinary N-telopeptide (uNTx) levels in the investigational arm
  • Time Frame: Baseline to Week 10
  • Safety Issue:
  • Measure: Mean percentage change in sCTx levels in the investigational arm
  • Time Frame: Baseline to End of Chemotherapy (Week 20)
  • Safety Issue:
  • Measure: Mean percentage change in bALP levels in the investigational arm
  • Time Frame: Baseline to End of Chemotherapy (Week 20)
  • Safety Issue:
  • Measure: Mean percentage change in uNTx levels in the investigational arm
  • Time Frame: Baseline to End of Chemotherapy (Week 20)
  • Safety Issue:
  • Measure: Mean percentage change in serum bone-specific alkaline phosphatase (bALP) in the placebo arm.
  • Time Frame: Baseline to Week 10
  • Safety Issue:
  • Measure: Mean percentage change in urinary N-telopeptide (uNTx) levels in the placebo arm.
  • Time Frame: Baseline to Week 10
  • Safety Issue:
  • Measure: Mean percentage change in sCTx levels in the levels in the placebo arm.
  • Time Frame: Baseline to End of Chemotherapy (Week 20)
  • Safety Issue:
  • Measure: Mean percentage change in bALP levels in the levels in the placebo arm.
  • Time Frame: Baseline to End of Chemotherapy (Week 20)
  • Safety Issue:
  • Measure: Mean percentage change in uNTx levels in the levels in the placebo arm.
  • Time Frame: Baseline to End of Chemotherapy (Week 20)
  • Safety Issue:
  • Measure: Time to first on study symptomatic skeletal related events
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: Progression free survival rate
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: Progression free survival rate
  • Time Frame: 18 months
  • Safety Issue:
  • Measure: Overall survival rate
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: Overall survival rate
  • Time Frame: 18 months
  • Safety Issue:
  • Measure: Number of participants with side effects in the investigational drug arm
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: Number of participants with side effects in the placebo arm
  • Time Frame: 2 years
  • Safety Issue:

Estimated Enrollment: 50

Study Start Date: September 4, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Histologically or cytologically confirmed urothelial carcinoma (kidney, ureter, bladder) with metastatic disease involving the bones, not amenable to curative treatment
  • Mixed histologies permitted as long as urothelial histology is the major component Presence of one or more bone metastases
  • No prior systemic chemotherapy for metastatic disease (immunotherapy permitted)
  • Starting first line chemotherapy for metastatic urothelial cancer with gemcitabine and cisplatin or gemcitabine and carboplatin and planned to receive 4-6 cycles
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Adequate renal function
  • Acceptable serum calcium or albumin-adjusted serum calcium
  • Adequate hepatic function
  • Patients all require oral examination and appropriate preventative dentistry prior to starting treatment
  • Expected life expectancy of at least 3 months

Exclusion Criteria:

  • Prior chemotherapy for metastatic disease
  • Current or prior IV bisphosphonate or denosumab administration
  • Current or prior oral bisphosphonate administration to treat bone metastases
  • Unacceptable renal function
  • Abnormal bone metabolism (Paget's disease)
  • Untreated or symptomatic brain metastases
  • Patients with a history of other malignancies, with exceptions
  • Significant dental/oral disease
  • Administration of other prior anticancer therapies within 2 weeks of randomization
  • Patient is pregnant or breast feeding, or planning to become pregnant within 7 months after the end of treatment
  • Female of child bearing potential is not willing to use, in combination with her partner, highly effective contraception during treatment and for 7 months after the end of treatment
  • Known sensitivity to any of the products to be administered during the study
  • History of any other clinically significant disorder, condition or disease that in the opinion of the investigator excludes the patient

Contact:

  • Srikala Sridhar, M.D.
  • 416-946-4501 Ext. 2662

Location:

  • Princess Margaret Cancer Centre
  • Toronto Ontario M5G 2M9 Canada

View trial on ClinicalTrials.gov


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Cabozantinib Plus Pembrolizumab as First-Line Therapy for Cisplatin-Ineligible Advanced Urothelial Carcinoma (PemCab)


Condition: Metastatic Urothelial Carcinoma, Bladder Cancer

Intervention:

  • Drug: Cabozantinib
  • Drug: Pembrolizumab

Purpose: This is an open label, non-randomized phase 2 study of the combination of pembrolizumab and cabozantinib to assess overall response rate (ORR), progression free survival at 6 months (PFS6), and overall survival (OS) in patients with metastatic urothelial carcinoma (UC) ineligible for cisplatin.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03534804

Sponsor: University of Utah

Primary Outcome Measures:

  • Measure: Overall Response Rate (ORR)
  • Time Frame: 12 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Progression-free survival (PFS) at 6 months (PFS6)
  • Time Frame: 6 months
  • Safety Issue:
  • Measure: Overall Survival (OS)
  • Time Frame: Patients are expected to stay on treatment for approximately 12 months; 18 months
  • Safety Issue:
  • Measure: Occurrence of Adverse Events and Serious Adverse Events
  • Time Frame: 12 months
  • Safety Issue:

Estimated Enrollment: 39

Study Start Date: September 18, 2018

Phase: Phase 2

Eligibility:

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

Eligibility Criteria:

  1. for consideration of treatment with immunotherapy using a checkpoint inhibitor following surgical resection. Treatment

Inclusion Criteria:

  • Histologically proven muscle-invasive transitional cell or urothelial carcinoma.
  • Metastatic (any N+ or M1) or locally advanced, unresectable (T4bN0) disease.
  • Measurable disease is required as determined by RECIST v1.1.
  • Performance Status ECOG 0-2
  • Cisplatin-ineligibility based on ≥1 of the following:
  • Estimated creatinine clearance between ≥30 and <60 ml/min (Cockcroft-Gault formula)
  • ECOG PS>1
  • Hearing loss
  • Baseline neuropathy > grade 1.
  • Patient refusal
  • Be greater to or equal to 18 years of age on day of signing informed consent.
  • Adequate organ function as defined in the protocol
  • Serum albumin ≥ 2.8 g/dl
  • Alkaline phosphatase (ALP) ≤ 3 × upper limit of normal (ULN). ALP ≤ 5 × ULN with documented bone metastases.
  • Negative serum or urine pregnancy test at screening for women of childbearing potential.
  • Highly effective contraception for both male and female subjects throughout the study and for at least 120 days after last pembrolizumab treatment administration if the risk of conception exists.
  • Must have recovered from adverse effects of any prior surgery, radiotherapy or other antineoplastic therapy.
  • Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy. Alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
  • Last dose of any radiation therapy ≥ 2 weeks before first dose of study treatment.
  • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria:

  • Previous systemic chemotherapy treatment for urothelial carcinoma, with the exception of perioperative chemotherapy treatment alone or with concurrent radiation within 6 months prior to treatment.
  • Small-cell or sarcomatoid component in histology
  • Has received prior treatment with cabozantinib.
  • Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
  • Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or other checkpoint inhibitors in the adjuvant setting.
  • Radiation therapy for bone metastasis ≤ 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
  • 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 4 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. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel). Allowed anticoagulants are the following:
  • Low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted.
  • Low-dose low molecular weight heparins (LMWH) are permitted.
  • Anticoagulation with therapeutic doses of LMWH is allowed in subjects without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
  • The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 × ULN within 7 days before the first dose of study treatment.
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders:
  • Ongoing congestive heart failure exacerbation or New York Heart Association Class 4, unstable angina pectoris, serious cardiac arrhythmias.
  • Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment.
  • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before first dose.
  • Class 3 congestive heart failure
  • Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
  • The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
  • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose.
  • Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose.
  • Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
  • Lesions invading or encasing any major blood vessels.
  • Other clinically significant disorders that would preclude safe study participation.
  • Serious non-healing wound/ulcer/bone fracture.
  • Uncompensated/symptomatic hypothyroidism.
  • Moderate to severe hepatic impairment (Child-Pugh B or C).
  • Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before first dose and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment. Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
  • Diagnosis of another malignancy within 2 years before first dose of study treatment, with the exception of those determined by the treating investigator to have a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, ductal carcinoma in situ treated surgically with curative intent, localized prostate cancer treated with curative intent and/or no intent for further treatment, or incidental prostate cancer)
  • Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, intranasal, inhaled, topical steroids, or local steroid injection) is not considered an exclusion.
  • Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent per treating physician's clinical judgment. Subjects with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
  • Prior organ transplantation including allogenic stem-cell transplantation.
  • Has known history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Active and inactive vaccinations within 4 weeks of the first dose of pembrolizumab and while on trial is prohibited.
  • Known prior severe hypersensitivity to investigational products or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3).
  • 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.
  • Subjects taking prohibited medications as described in Section 6.8. A washout period of prohibited medications for a period of at least two weeks or as clinically indicated should occur prior to the start of treatment.
  • Inability to swallow tablets or evidence of impaired intestinal absorption Previous systemic chemotherapy treatment for urothelial carcinoma, with the exception of perioperative chemotherapy treatment alone or with concurrent radiation within 6 months prior to treatment.

Contact:

  • Jill Broghammer
  • 801-213-6232

Location:

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

View trial on ClinicalTrials.gov


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


Condition: Bladder Cancer

Intervention:

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

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03520491

Sponsor: Memorial Sloan Kettering Cancer Center

Primary Outcome Measures:

  • Measure: number of patients who proceed to radical cystectomy and pelvic lymph node dissection
  • Time Frame: within 60 days after completion of neoadjuvant nivolumab or nivolumab in combination with ipilimumab
  • Safety Issue:

Estimated Enrollment: 45

Study Start Date: April 25, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Histologically confirmed diagnosis of urothelial carcinoma of the bladder. Variant histology is acceptable if there is a predominant urothelial component.
  • Cystoscopically and radiographically confirmed cT2-4a cN0 cM0 disease. Patients with cT4a disease invading into the prostatic stroma with no cystoscopic confirmation of muscle invasion are eligible.
  • Patients ineligible for cisplatin based on any of the following criteria:
  • Estimated or calculated creatinine clearance ≥ 30ml/min but < 60 ml/min
  • Grade 2 or above audiometric hearing loss (per CTCAE v4.0)
  • Grade 2 or above peripheral neuropathy (per CTCAE v4.0)
  • Availability of tumor specimen block or 30 unstained slides from diagnosis of muscle-invasive disease. Patients with fewer than 30 slides available may be enrolled after discussion with the Principal Investigator.
  • Karnofsky performance status ≥ 70%.
  • 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 vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, 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.
  • Serious, non-healing wound, ulcer, or bone fracture.
  • Other prior malignancy active within the previous 2 years except for local or organ-confined early stage cancer that has been definitively treated with curative intent or does not require treatment, does not require ongoing treatment, has no evidence of active disease, and has a negligible risk of recurrence and is therefore unlikely to interfere with the endpoints of the study.
  • Subjects who have received prior therapy with any T cell co-stimulation or checkpoint pathways such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137; or other medicines specifically targeting T cells are prohibited. Prior IL-2 is permitted.
  • Prior therapy with intravesical BCG within 6 weeks of treatment.
  • Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • History of allergy to study drug component or history of severe hypersensitivity reaction to any monoclonal antibody.
  • Women who are breastfeeding or pregnant as evidenced by a positive pregnancy test within 14 days of first dose.
  • Male subjects who are unwilling to use contraception during the treatment and for at least 31 weeks after the last dose of study treatment (5 half-lives of study drug plus 90 days duration of sperm turnover).
  • Women of childbearing potential (WOCBP) not using a medically acceptable means of contraception throughout the study treatment and for at least 23 weeks following the last dose of study treatment (5 half-lives of study drug plus 30 days duration of ovulatory cycle).
  • WOCBP are defined as those who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post-menopausal is defined as:
  • Amenorrhea ≥ 12 consecutive months without another cause, or
  • For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
  • Inability to comply with study and/or follow-up procedures.

Contact:

  • Min Yuen Teo, MB BCh
  • 914-367-7393

Locations:

  • Memoral Sloan Kettering Basking Ridge
  • Basking Ridge New Jersey 07920 United States
  • Memorial Sloan Kettering Westchester
  • Harrison New York 10604 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States

View trial on ClinicalTrials.gov


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Phase I Study of MK-3475 in Combination With BCG for Patients With High Risk Superficial Bladder Cancer


Condition: Bladder Cancer

Intervention:

  • Drug: Intravenous MK-3475/ Intravesical BCG

Purpose: This is a single center Phase I safety and efficacy study of MK-3475 therapy used in combination with bladder infused BCG treatment for patients, 18 years or older, with high risk superficial bladder cancer (cancer not yet involving the muscle of the bladder wall) who have had removal of their bladder tumor. Patients will be enrolled to a single treatment group of a fixed dose of MK 3475 and BCG.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02324582

Sponsor: Southern Illinois University

Primary Outcome Measures:

  • Measure: safety (Grade and quantity of adverse events)
  • Time Frame: change from baseline to 23 weeks
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Complete Response Rate (cytoscopy)
  • Time Frame: change from baseline to 19 weeks; 3, 12, and 24 months post treatment completion
  • Safety Issue:
  • Measure: Change in Quality of Life
  • Time Frame: change from baseline to 10 weeks, 19 weeks and 3, 12, and 24 months post-Week 19 cystectomy
  • Safety Issue:
  • Measure: Change in Quality of Life
  • Time Frame: change from baseline to 10 weeks, 19 weeks and 3, 12, and 24 months post-Week 19 cystectomy
  • Safety Issue:

Estimated Enrollment: 15

Study Start Date: June 2015

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  1. 1.Willing and able to provide written informed consent/assent. 2.18 years of age. 3.Have pathologically documented high grade transitional cell superficial bladder cancer (Ta, T1) at time of restaging, or have pathologically documented high grade CIS of the bladder at time of initial resection for recurrent/persistent high risk transitional cell superficial bladder cancer. 4.Recurrent/persistent disease despite 2 Induction Intravesical Therapy Courses given within 12 months (with BCG being one of them), or despite one induction BCG treatment in addition to at least one maintenance course of BCG 5.Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion. 6.ECOG performance status of 0-
  2. 7.Demonstrate adequate organ function 8.Female subject of childbearing potential should have a negative urine or serum pregnancy. 9.Female subjects of childbearing potential should be willing to use 2 methods of birth control or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication 10.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:

  1. Currently has active or progressive metastatic disease.
  2. 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.
  3. 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.
  4. 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. Prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy for bladder cancer.
  6. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  7. Known additional malignancy that is progressing or requires active treatment.
  8. Active autoimmune disease that has required systemic treatment in past 2 years.
  9. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  10. Active infection, including a concurrent febrile illness, requiring systemic therapy.
  11. 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. 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 4 months 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) including anti-CD40 and anti-OX40 antibodies.
  15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  16. Has known active Hepatitis B (e.g., HBs Ag reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  17. Has known active tuberculosis. Subjects will not be specifically tested for the study; however, subjects that are tested within 28 days of beginning study or while on study and test positive with the PPD test before treatment should have active tuberculosis ruled out before therapy begins for their superficial bladder cancer.
  18. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
  19. Has an active urinary tract infection, gross hematuria, or known broken mucosal barrier of the bladder.
  20. Less than 14 days post bladder biopsy, TUR, or traumatic catheterization.
  21. Evidence of muscle invasive bladder cancer, or transitional cell carcinoma of the upper urinary tract

Contact:

  • Sherjeel Sana, MD
  • 217-545-7969

Locations:

  • Simmons Cancer Institute-SIU School of Medicine
  • Springfield Illinois 62702 United States
  • Southern Illinois University School of Medicine
  • Springfield Illinois 62702 United States

View trial on ClinicalTrials.gov


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Phase 1B Study to Assess Safety and Efficacy of Neo-Adjuvant Bladder Urothelial Carcinoma COmbination-immunotherapy (NABUCCO)


Condition: Urothelial Carcinoma

Intervention:

  • Drug: Ipilimumab
  • Drug: Nivolumab

Purpose: In this single-arm trial we will investigate the safety of short-term preoperative therapy with ipilimumab and nivolumab in patients with high-risk resectable urothelial cancer. We will determine the number of patients that have surgical resection <12 weeks from first infusion, as this is an endpoint that is clinically meaningful for this population. 24 patients will be included. All patients will be receiving a sequenced scheme of Nivolumab and Ipilimumab.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03387761

Sponsor: The Netherlands Cancer Institute

Primary Outcome Measures:

  • Measure: Number of patients that have surgical resection <12 weeks after study start
  • Time Frame: At 12 weeks
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Efficacy of immunotherapy, assessed by by the percentage of pathological complete response rate (pCR) at cystectomy
  • Time Frame: At 12 weeks
  • Safety Issue:
  • Measure: Differences in immune infiltrates in responders vs nonresponders
  • Time Frame: At 12 weeks
  • Safety Issue:
  • Measure: T-cell (dys)functionality as measured by comparing the transcriptome of tumor-specific T cells in intra-patient pre- and post therapy tissue
  • Time Frame: At 12 weeks
  • Safety Issue:
  • Measure: Explore whether radiomics-based predictive models can be established for immunotherapy responders vs non-responders
  • Time Frame: at 12 weeks
  • Safety Issue:

Estimated Enrollment: 24

Study Start Date: January 15, 2018

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  1. Willing and able to provide informed consent
  2. Age ≥ 18 years
  3. High-risk resectable urothelial cancer (upper urinary tract allowed) defined as stage III UC: cT3-4aN0M0 OR cT1-4aN1-3M0
  4. Refusal of neoadjuvant/induction cisplatin-based chemotherapy or patients in whom neoadjuvant cisplatin based therapy is not appropriate.
  5. World Health Organization (WHO) performance Status 0 or
  6. Urothelial cancer is the dominant histology (>70%).
  7. Formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks from diagnostic TUR available
  8. Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥1.0x109/L, Platelets ≥100 x109/L, Hemoglobin ≥5.5 mmol/L, GFR>30 ml/min, AST ≤ 2.5 x ULN, ALT ≤2.5 x ULN, Bilirubin ≤1.5 X ULN
  9. Negative pregnancy test within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential.
  10. 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 180 days after the last dose of immunotherapy Adequate contraceptive methods are: condom, sterilization, other barrier contraceptive measures preferably in combination with condoms, oral contraceptives, intra-uterine device.

Exclusion Criteria:

  1. Subjects with active autoimmune disease in the past 2 years. Patients with diabetes mellitus, properly controlled hypothyroidism or hyperthyroidism, vitiligo, psoriasis or other mild skin disease can still be included.
  2. Documented history of severe autoimmune disease (e.g. inflammatory bowel disease, myasthenia gravis).
  3. Prior CTLA-4 or PD-1/PD-L1-targeting immunotherapy.
  4. Known history of Human Immunodeficiency Virus, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA), active tuberculosis, or other active infection requiring therapy at the time of inclusion.
  5. Underlying medical conditions that, in the investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of adverse events
  6. Medical condition requiring the use of immunosuppressive medications, 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. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) will be allowed.
  7. Use of other investigational drugs before study drug administration
  8. Malignancy, other than urothelial cancer, in the previous 2 years, with a high chance of recurrence (estimated >10%). Patients with low risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.
  9. Pregnant and lactating female patients.
  10. 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.
  11. 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.
  12. 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.
  13. Previous intravenous chemotherapy for bladder cancer. Prior chemoradiation is allowed.
  14. Patients in whom use of a colon segment for urinary diversion is planned

Contact:

  • Michiel MS van der Heijden, Dr.
  • +3120 512 9111

Location:

  • Antoni van Leeuwenhoek ziekenhuis
  • Amsterdam NH 1066CX Netherlands

View trial on ClinicalTrials.gov


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A Phase 2, Open-label Study of Rucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma


Condition: Bladder Cancer, Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Renal Pelvis Carcinoma, Ureter Carcinoma, Urinary Bladder Carcinoma, Urethra Carcinoma, Muscle Invasive Bladder Cancer

Intervention:

  • Drug: Rucaparib

Purpose: The purpose of the ATLAS study is to determine how patients with locally advanced unresectable or metastatic urothelial carcinoma respond to treatment with rucaparib.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03397394

Sponsor: Clovis Oncology, Inc.

Primary Outcome Measures:

  • Measure: Objective response rate (ORR)
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years)
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Duration of response (DOR)
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years)
  • Safety Issue:
  • Measure: Progression-free survival (PFS)
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years)
  • Safety Issue:
  • Measure: Overall survival (OS)
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years and 6 months)
  • Safety Issue:
  • Measure: Number of participants with treatment-related Adverse Events (AEs) as assessed by CTCAE v4.03 as a measure of safety and tolerability
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years and 6 months)
  • Safety Issue:
  • Measure: Number of participants with serious AEs as a measure of safety and tolerability
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years and 6 months)
  • Safety Issue:
  • Measure: Number of participants with worsening laboratory values as a measure of safety and tolerability
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years and 6 months)
  • Safety Issue:
  • Measure: Trough plasma PK (Cmin) of rucaparib based on sparse sampling
  • Time Frame: From enrollment to primary completion of study (up to approximately 2 years and 6 months)
  • Safety Issue:

Estimated Enrollment: 200

Study Start Date: June 1, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Have histologically or cytologically confirmed locally advanced unresectable or metastatic transitional cell carcinoma of the urothelium (renal pelvis, ureter, urinary bladder or urethra)
  • Received 1 or 2 prior treatment regimens for advanced or metastatic disease
  • Confirmed radiologic disease progression during or following recent treatment
  • Mandatory biopsy is required during screening
  • Measurable disease per RECIST v1.1
  • Adequate organ function
  • ECOG 0 or 1

Exclusion Criteria:

  • Prior treatment with a PARP inhibitor
  • Symptomatic and/or untreated CNS metastases
  • Duodenal stent and/or any gastrointestinal disorder that may interfere with absorption of rucaparib

Contact:

  • Clovis Oncology Clinical Trial Navigation
  • 1-855-262-3040 (USA)

Locations:

  • Pinnacle Oncology, Honor Health
  • Scottsdale Arizona 85258 United States
  • University of California San Diego (UCSD), Moores Cancer Center
  • La Jolla California 92093 United States
  • University of California, Los Angeles (UCLA)
  • Los Angeles California 90095 United States
  • Universityof California, Irvine
  • Orange California 92868 United States
  • Saint John's Health Center - John Wayne Cancer Institute (JWCI)
  • Santa Monica California 90404 United States
  • Stanford University School of Medicine
  • Stanford California 94304 United States
  • Hartford Health Care Cancer Institute
  • Hartford Connecticut 06102 United States
  • Eastern Connecticut Hematology & Oncology Associates (ECHO)
  • Norwich Connecticut 06360 United States
  • Medstar Georgetown University Medical Center
  • Washington District of Columbia 20007 United States
  • Miami Cancer Institute, Baptist Health South Florida
  • Miami Florida 33176 United States
  • Northwestern University, Chicago
  • Chicago Illinois 60611 United States
  • Indiana University - Melvin and Bren Simon Cancer Center (IUSCC)
  • Indianapolis Indiana 46202 United States
  • The University of Iowa and Holden Comprehensive Cancer Center
  • Iowa City Iowa 52242 United States
  • Norton Cancer Center
  • Louisville Kentucky 40207 United States
  • Ochsner Cancer Institute
  • New Orleans Louisiana 70121 United States
  • University of Maryland, Marlene and Stewart Greenebaum Cancer Center
  • Baltimore Maryland 21201 United States
  • University of Michigan
  • Ann Arbor Michigan 48109 United States
  • Minnesota Oncology Hematology P.A. (USO - US Oncology)
  • Minneapolis Minnesota 55404 United States
  • Comprehensive Cancer Centers of Nevada (CCCN)
  • Las Vegas Nevada 89169 United States
  • John Theurer Cancer Center at Hackensack University Medical Center
  • Hackensack New Jersey 07601 United States
  • University of New Mexico UNM Cancer Research and Treatment Center
  • Albuquerque New Mexico 87102 United States
  • New York Oncology Hematology, P.C. (USO - US Oncology)
  • Albany New York 12208 United States
  • Roswell Park Cancer Institute
  • Buffalo New York 14263 United States
  • New York - Presbyterian Hospital-Weill Cornell Medical Center
  • New York New York 10021 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States
  • Duke University, Duke Cancer Institute
  • Durham North Carolina 27710 United States
  • Stephenson Cancer Center
  • Oklahoma City Oklahoma 73104 United States
  • Northwest Cancer Specialists P.C. (USO - US Oncology)
  • Portland Oregon 97062 United States
  • Providence Portland Medical Center
  • Portland Oregon 97213 United States
  • Oregon Health and Science University
  • Portland Oregon 97239 United States
  • Lehigh Valley Health Network
  • Allentown Pennsylvania 18103 United States
  • Penn State Hershey Medical Center
  • Hershey Pennsylvania 17033 United States
  • Atlantic Urology Clinics
  • Myrtle Beach South Carolina 29572 United States
  • University Oncology & Hematology
  • Chattanooga Tennessee 37403 United States
  • Urology Associates
  • Nashville Tennessee 37209 United States
  • Texas Oncology PA (USO - US Oncology)
  • Dallas Texas 76201 United States
  • University of Texas, UT Health Science Center
  • Houston Texas 77030 United States
  • University of Utah, Huntsman Cancer Institute
  • Salt Lake City Utah 84112 United States
  • University of Virginia, Emily Couric Clinical Center
  • Charlottesville Virginia 22908 United States
  • University of Washington / Seattle Cancer Care Alliance
  • Seattle Washington 98109 United States
  • Froedtert & Medical College of Wisconsin
  • Milwaukee Wisconsin 53226 United States
  • Centre de Lutte Contre le Cancer (CLCC) - Universite de Lyon - Centre Leon-Berard
  • Lyon 69008 France
  • Hopital Saint-Louis
  • Paris 75010 France
  • Centre de Lutte Contre le Cancer - Institut de Cancerologie de l'Ouest - Rene Gauducheau
  • Saint-Herblain 44805 France
  • Institut Universitaire du Cancer de Toulouse - Oncopole
  • Toulouse 31059 France
  • Institut Gustave Roussy
  • Villejuif 94805 France
  • Urologische und Kinderurologische Universitätsklinik im Malteser
  • Erlangen 91054 Germany
  • Universitatsklinikum Munster / Urologie und Kinderurologie
  • Münster 26133 Germany
  • Studienpraxis Urologie
  • Nurtingen 72622 Germany
  • Fondazionerca sul Cancro ONLUS - Istituto di Candiolo IRCCS
  • Candiolo 10060 Italy
  • IRCCS Ospedale San Raffaele - Medical Oncology Dept
  • Milano 20132 Italy
  • Fondazione IRCCS Istituto Nazionale Tumori
  • Milano 20133 Italy
  • Azienda Ospedaliera Universitaria Federico II Oncologia Medica
  • Naples 80131 Italy
  • Universidad de Navarra - Clinica Universitaria de Navarra
  • Pamplona Navarre 31008 Spain
  • Hospital del Mar
  • Barcelona 08003 Spain
  • Hospital Santa Creu i Sant Pau
  • Barcelona 08025 Spain
  • Hospital Universitari Vall d'Hebron de Barcelona
  • Barcelona 08035 Spain
  • Hospital General Universitario Gregorio Maranon
  • Madrid 28007 Spain
  • Clinica Universitaria de Navarra Madrid
  • Madrid 28027 Spain
  • MD Anderson Cancer Center
  • Madrid 28033 Spain
  • Hospital Universitario 12 de Octubre
  • Madrid 28041 Spain
  • Hospital Clínico Universitario de Santiago de Compostela
  • Santiago De Compostela 15706 Spain
  • Sarah Cannon Research Institute - United Kingdom - London Office
  • London CH63 4JY United Kingdom
  • Guy's & St. Thomas' Hospital (London Oncology Clinic)
  • London W1G 6AF United Kingdom

View trial on ClinicalTrials.gov


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Phase 2 Trial of Olaparib in Patients With Metastatic Urothelial Cancer Harboring DNA Damage Response Gene Alterations


Condition: Metastatic Urothelial Cancer

Intervention:

  • Drug: Olaparib

Purpose: This is a single arm open label multi-institutional phase II trial of olaparib monotherapy in subjects with metastatic urothelial cancer harboring somatic DNA damage response (DDR) alterations. The primary objective of the study is to estimate the objective response rate (per RECIST 1.1) to treatment with olaparib.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03448718

Sponsor: Matthew Galsky

Primary Outcome Measures:

  • Measure: Objective Response Rate
  • Time Frame: 36 Months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Progression-Free Survival
  • Time Frame: 36 Months
  • Safety Issue:

Estimated Enrollment: 30

Study Start Date: April 17, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Age ≥ 18 years at the time of consent.
  • ECOG Performance Status of ≤ 1 within 14 days prior to registration. Cisplatin-ineligible chemotherapy-naïve subjects (see inclusion criteria #8) may have an ECOG Performance Status of ≤ 2.
  • Histological or cytological evidence/confirmation of urothelial cancer.
  • Metastatic and/or unresectable (cT4b) urothelial cancer.
  • Metastatic disease evaluable on imaging studies. Subjects may have measurable disease according to RECIST 1.1 or bone-only disease within 30 days prior to registration.
  • NOTE: Bone-only subjects are eligible if their disease can be documented/ evaluated by bone scans, CT or MRI. Their disease will be assessed using MD Anderson criteria.34
  • NOTE: Previously irradiated lesions are eligible as a target lesion only if there is documented progression of the lesion after irradiation.
  • Somatic alteration in one of the following DDR genes as determined by genomic sequencing performed in a Clinical Laboratory Improvement Amendments (CLIA) laboratory. Somatic alterations will include nonsense, frameshift, splice-site or missense mutations or homozygous deletions. Subjects with alterations in DDR genes not included in the list below will be considered on a case by case basis after discussion with the sponsor-investigator. Subjects with germline alterations in DDR genes will be considered on a case by case basis and will be reviewed by the sponsor-investigator. At least 6 subjects will have BRCA or ATM alterations.
  • Nucleotide Excision Repair: ERCC2, ERCC3,ERCC4, ERCC5, ERCC6
  • Homologous Recombination: BRCA1, RAD52, BRCA2, RAD54L, RAD50, NBN RAD51, MRE11A, RAD51B, RAD51D, RAD51C, CTIP
  • DNA Sensor: ATM, ATR, MDC1, ATRX, CHEK1, CHEK2
  • Fanconi Anemia Pathway: PALB2, FANCE, BRIP1, FANCF, FANCA, FANCG FANCB, BLM, FANCC, FANCD2
  • Base Excision Repair: XRCC2, XRCC3, XRCC4, XRCC5, XRCC6
  • Other: MUTYH, RECQL4, POLQ, POLE, WRN
  • A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic
  • Subjects must have progressed despite at least 1 prior line of treatment for metastatic and/or unresectable urothelial cancer. However, cisplatin-ineligible (defined by a calculated creatinine clearance of >30 but < 60 mL/min OR CTCAE v4 Grade ≥ 2 audiometric hearing loss OR CTCAE v4 Grade ≥ 2 peripheral neuropathy OR ECOG PS = 2), and chemotherapy-naïve subjects are also eligible.
  • Prior cancer treatment (systemic therapy or radiation therapy) must be completed at least 3 weeks prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to Grade ≤ 1 or baseline.
  • Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration.
  • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
  • Hemoglobin (Hgb) ≥ 10 g/dL
  • Platelets ≥ 100 x 109/L
  • Calculated creatinine clearance ≥ 30 mL/min
  • Bilirubin ≤ 1.5 × upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases)
  • Alanine aminotransferase (ALT) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases)
  • Female subjects must be postmenopausal or there must be evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.
  • Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of highly effective methods of contraception from the time of informed consent until 30 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method. Males must be willing to abstain from heterosexual activity or to use 2 forms of highly effective methods of contraception from the time of informed consent until 90 days after treatment discontinuation.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
  • All subjects must have adequate archival tissue available prior to registration (i.e., at least 15 unstained slides or paraffin block). Archival tissue should represent invasive or metastatic urothelial cancer with a preference for metastatic tissue if available. Subjects without adequate tissue may be considered on a case by case basis after discussion with the sponsor-investigator.

Exclusion Criteria:

  • 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).
  • Known additional malignancy that is active and/or progressive requiring treatment; subjects with other malignancies that have been definitively treated and who have been rendered disease free will be eligible.
  • Prior treatment with a PARP inhibitor, including olaparib.
  • Treatment with any investigational drug within 30 days prior to registration.
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
  • Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
  • Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
  • Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
  • Subjects with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
  • Major surgery within 2 weeks of starting study treatment and subjects must have recovered from any effects of any major surgery.
  • Subjects considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan, history of pneumonitis, or any psychiatric disorder that prohibits obtaining informed consent.
  • Subjects unable to swallow orally administered medication and subjects with gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Immunocompromised subjects, e.g., subjects who are known to be serologically positive for human immunodeficiency virus (HIV).
  • Subjects with a known hypersensitivity to olaparib or any of the excipients of the product.
  • Subjects with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
  • Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)

Contact:

  • Matthew Galsky, MD
  • 212-824-5452

Locations:

  • University of Chicago Medical Center
  • Chicago Illinois 60637 United States
  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
  • Baltimore Maryland 21287 United States
  • Karmanos Cancer Center (Wyane State University)
  • Detroit Michigan 48201 United States
  • Icahn School of Medicine at Mount Sinai
  • New York New York 10029-6542 United States
  • University of North Carolina at Chapel Hill
  • Chapel Hill North Carolina 27599 United States
  • Vanderbilt-Ingran Cancer Center
  • Nashville Tennessee 37232 United States
  • Huntsman Cancer Institute University of Utah
  • Salt Lake City Utah 84112-5550 United States

View trial on ClinicalTrials.gov


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A Phase 1 Dose-Escalation Study of Intravesical MK-3475 and Bacillus Calmette-Guerin (BCG) in Subjects With High Risk and BCG-Refractory Non-Muscle-Invasive Bladder Cancer


Condition: Recurrent Bladder Carcinoma, Stage 0a Bladder Urothelial Carcinoma, Stage 0is Bladder Urothelial Carcinoma, Stage I Bladder Cancer

Intervention:

  • Biological: BCG Solution
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab
  • Other: Pharmacological Study

Purpose: The purpose of this study is to evaluate the efficacy (the effect of drug on tumor) and the tolerability (the effect of drug on the body) of pembrolizumab, when given as a single agent in patients with bladder tumors. Another purpose of the study is to see what tumor characteristics are associated with increased efficacy of the pembrolizumab. Pembrolizumab (MK-3475) is an antibody (a human protein that sticks to a part of the tumor and/or immune cells) designed to allow the body's immune system to work against tumor cells. Pembrolizumab is Food and drug Administration (FDA) approved for the treatment of advanced melanoma (a type of skin cancer) and some types of lung cancer. It is not yet approved by the United States Food and Drug Administration (USFDA) for bladder cancer, hence it is considered an investigational agent for this disease.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02808143

Sponsor: Northwestern University

Primary Outcome Measures:

  • Measure: Maximum Tolerated Dose (MTD)
  • Time Frame: Up to 9 weeks
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Dose Limiting Toxicities (DLTs)
  • Time Frame: Up to 9 weeks
  • Safety Issue:
  • Measure: Incidence of adverse events
  • Time Frame: Up to 30 days from the last dose of study drug
  • Safety Issue:

Estimated Enrollment: 27

Study Start Date: February 10, 2017

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • Patients must have a histologically documented recurrence of non-muscle-invasive bladder carcinoma (T1HG, T1HG after repeat transurethral resection [reTUR]) or BCG refractory; if patient has received BCG they can be Ta, Tis, or T1)
  • Patients must have persistent high grade disease OR be BCG refractory, defined as either:
  • Recurrence within 6 months of receiving at least 2 courses of intravesical BCG (at least 5 or 6 inductions and at least 2 or 3 maintenance doses) or
  • T1 high grade disease at the first evaluation following induction BCG alone (at least 5 of 6 induction doses)
  • Patients must agree to provide tissue from archival biopsy samples or newly obtained excisional biopsy of a tumor lesion
  • NOTE: Patients who do not have available specimens from previous biopsy or do not agree to provide this tissue are not eligible; cytological specimens will not be acceptable; availability of tissue must be confirmed at the time of registration, but the actual sample does not have to be received in order to complete registration
  • Patients must have received one course of induction treatment with BCG (4-6 weekly doses), irrespective of the interval since last treatment; patients are allowed to have received any number of prior chemotherapy instillations
  • NOTE: Patients may have received prior intravesical interferon
  • All patients must have imaging (computed tomography [CT] scan or magnetic resonance imaging [MRI]) documenting normal upper urinary tracts and absence of locally advanced bladder cancer within 60 days prior to study registration
  • Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
  • Absolute neutrophil count (ANC) >= 1,500 /mcL within 14 days prior to registration
  • Platelets >= 100,000 / mcL within 14 days prior to registration
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L within 14 days prior to registration
  • Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated (creatinine clearance should be calculated per institutional standard) creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN within 14 days prior to registration
  • Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN within 14 days prior to registration
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN within 14 days prior to registration
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants within 14 days prior to registration
  • Activated PTT (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 within 14 days prior to registration
  • Females of child-bearing potential (FOCBP) and males must agree to use adequate contraception (e.g. hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 120 days following completion of therapy; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately;
  • NOTE: A FOCBP is any woman (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
  • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
  • FOCBP must have a negative urine or serum pregnancy test within 7 days 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
  • Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Exclusion Criteria:

  • Patients who have had chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day -14 or who have not recovered (to =< grade 1 or baseline) from adverse events due to a previously administered agent are not eligible
  • Note: subjects with =< grade 2 neuropathy are an exception to this criterion and do qualify for the study
  • Note: if subject received major surgery within 4 weeks prior to day -14, they must have recovered adequately from the toxicity and/or complications per PI discretion
  • Patients may not be receiving any other investigational agents within 4 weeks of the first dose of treatment
  • Patients who have received a prior monoclonal antibody within 4 weeks prior to study day -14 or who have not recovered (to =< grade 1 or baseline) from adverse events due to agents administered more than 4 weeks earlier are not eligible
  • Patients who have a diagnosis of immunodeficiency (per PI discretion) or who have received treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents within 2 weeks prior to study registration are not eligible
  • NOTE: patients who have received acute, low-dose, systemic immunosuppressant medications (eg, one-time dose of dexamethasone for nausea) may be enrolled in the study; the use of inhaled corticosteroids and mineralocorticoids (eg, fludrocortisone) is allowed
  • Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475 are not eligible AND/OR patients who have had prior exposure to compounds of similar chemical or biologic composition to MK-3475 are not eligible
  • Patients who have documentation of an uncontrolled intercurrent illness (as noted in their medical records) including, but not limited to any of the following, are not eligible
  • Ongoing or active infection requiring systemic treatment
  • Symptomatic congestive heart failure (New York Heart Association cardiac disease class III or IV)
  • Unstable angina pectoris
  • Myocardial infarction within the previous 3 months
  • Unstable cardiac arrhythmias
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
  • Female patients who are pregnant or nursing are not eligible
  • Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to BCG are not eligible
  • Patients who have had an active infection requiring systemic therapy within 1 week prior to day -14 are not eligible UNLESS they are symptom-free and have a negative culture at the time of dosing on day -14
  • Patients who received a live, attenuated vaccine within 4 weeks before study registration or are anticipated to require such a live attenuated vaccine are not eligible; NOTE: 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 study registration or at any time during the study
  • Patients who are known to be (i.e. documented in medical records) human immunodeficiency virus (HIV) positive are not eligible
  • Patients with active tuberculosis are not eligible
  • Patients with known active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C are not eligible
  • NOTE: patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBc Ab] and absence of HBsAg) are eligible; HBV deoxyribonucleic acid (DNA) must be obtained in these patients 14 days prior to study registration
  • NOTE: patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
  • Patients who have a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins are not eligible
  • Patients with an active autoimmune disease requiring systemic treatment within 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
  • Patients with 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 Sjogren's syndrome will not be excluded from the study
  • Patients with history of interstitial lung disease or active, non-infectious pneumonitis are not eligible
  • NOTE: history of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Treatment with systemic immunostimulatory agents (including but not limited to IFNs, IL-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to study registration are not eligible
  • Patients who received prior treatment 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) are not eligible
  • Patients who have a history of prior malignancy are not eligible; please NOTE the following exceptions when patient has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy
  • Basal cell carcinoma of the skin
  • Squamous cell carcinoma of the skin
  • In situ cervical cancer
  • Patients who have a history of an allogeneic tissue/solid organ transplant are not eligible

Contact:

  • Study Coordinator
  • (312)695-1301

Location:

  • Northwestern University
  • Chicago Illinois 60611 United States

View trial on ClinicalTrials.gov


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A Phase 2, Randomized, Open-label Study of Nivolumab or Nivolumab/BMS-986205 Alone or Combined With Intravesical BCG in Participants With BCG-Unresponsive, High-Risk, Non-Muscle Invasive Bladder Cancer


Condition: Bladder Cancer, Bladder Tumors, Neoplasms, Bladder

Intervention:

  • Biological: Nivolumab
  • Biological: BCG
  • Drug: BMS-986205

Purpose: A study to evaluate Nivolumab or Nivolumab Plus Experimental Medication BMS-986205 with or without BCG in BCG-Unresponsive non-muscle invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03519256

Sponsor: Bristol-Myers Squibb

Primary Outcome Measures:

  • Measure: Proportion of carcinoma in situ (CIS) participants with complete response (CR), per Pathology Review Committee (PRC)
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Duration of complete response (DOCR), per PRC, in CIS participants with CR
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Event Free Survival (EFS), per PRC, for all non-CIS participants
  • Time Frame: Up to 5 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Progression-free Survival (PFS)
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Incidence of Adverse Events (AEs)
  • Time Frame: Up to 15 months
  • Safety Issue:
  • Measure: Incidence of Serious Adverse Events (SAEs)
  • Time Frame: Up to 15 months
  • Safety Issue:
  • Measure: Incidence of AEs leading to discontinuation
  • Time Frame: Up to 15 months
  • Safety Issue:
  • Measure: Incidence of deaths
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Incidence of laboratory abnormalities
  • Time Frame: Up to 15 months
  • Safety Issue:

Estimated Enrollment: 436

Study Start Date: May 25, 2018

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Pathologically demonstrated BCG-unresponsive, high-risk non-muscle-invasive bladder cancer (NMIBC) defined as CIS with or without papillary component, any T1, or Ta high-grade lesions
  • Predominant histologic component (> 50%) must be urothelial (transitional cell) carcinoma
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Exclusion Criteria:
  • Sign of locally advanced disease or metastatic bladder cancer
  • Urothelial cancer (UC) in the upper genitourinary tract (kidneys, renal collecting systems, ureters) within 24 months of enrollment
  • Prior immuno-oncology therapy Other protocol defined inclusion/

Exclusion Criteria:

  • Sign of locally advanced disease or metastatic bladder cancer
  • Urothelial cancer (UC) in the upper genitourinary tract (kidneys, renal collecting systems, ureters) within 24 months of enrollment
  • Prior immuno-oncology therapy Other protocol defined inclusion/exclusion criteria could apply

Contact:

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

Locations:

  • Local Institution
  • Phoenix Arizona 85054 United States
  • USC Norris Comprehensive Cancer Center
  • Los Angeles California 90033 United States
  • Local Institution
  • Riverside California 92505 United States
  • Local Institution
  • San Francisco California 94158 United States
  • Moffitt Cancer Center
  • Tampa Florida 33612 United States
  • Emory University
  • Atlanta Georgia 30322 United States
  • The University Of Chicago
  • Chicago Illinois 60637 United States
  • Local Institution
  • Westwood Kansas 66205 United States
  • Wichita Urology Group
  • Wichita Kansas 67226 United States
  • Local Institution
  • Shreveport Louisiana 71106 United States
  • Local Institution
  • Baltimore Maryland 21287 United States
  • Local Institution
  • Ann Arbor Michigan 48109 United States
  • Local Institution
  • Minneapolis Minnesota 55455 United States
  • Adult & Pediatric Urology
  • Omaha Nebraska 68114 United States
  • Deleware Valley Urology, LLC
  • Voorhees New Jersey 08043 United States
  • Local Institution
  • New York New York 10016 United States
  • Local Institution
  • New York New York 10032 United States
  • Local Institution
  • New York New York 10065 United States
  • James Cancer Hospital
  • Columbus Ohio 43212 United States
  • Local Institution
  • Springfield Oregon 97477 United States
  • MidLantic Urology
  • Bala-Cynwyd Pennsylvania 19004 United States
  • Local Institution
  • Hershey Pennsylvania 17033 United States
  • Medical University Of South Carolina
  • Charleston South Carolina 29425 United States
  • Carolina Urologic Research Center
  • Myrtle Beach South Carolina 29572 United States
  • Erlanger Health System
  • Chattanooga Tennessee 37403 United States
  • Local Institution
  • Nashville Tennessee 37232 United States
  • Urology Clinics Of North Texas, Pa
  • Dallas Texas 75231 United States
  • MD Anderson Cancer Center
  • Houston Texas 77030 United States
  • Local Institution
  • Lubbock Texas 79415 United States
  • Urology San Antonio Research, Pa
  • San Antonio Texas 78229 United States
  • Local Institution
  • Virginia Beach Virginia 23462 United States
  • Instituto Medico Especializado Alexander Fleming
  • Capital Federal Buenos Aires 1426 Argentina
  • Local Institution
  • Ciudad Autonoma Buenos Aires Buenos Aires 1118 Argentina
  • Hospital Britanico De Buenos Aires
  • Ciudad Autonoma de Buenos Aires Buenos Aires 1280 Argentina
  • Clinica Viedma S.A.
  • Viedma RIO Negro 8500 Argentina
  • Local Institution
  • Cordoba 5000 Argentina
  • Local Institution
  • Fortaleza Ceara 60130-241 Brazil
  • Local Institution
  • Porto Alegre RIO Grande DO SUL 91350-200 Brazil
  • Local Institution
  • Campinas SAN Paulo 13075-460 Brazil
  • Local Institution
  • Itacorubi, Florianopolis Santa Catarina 88034 Brazil
  • Local Institution
  • Jau SAO Paulo 17210-080 Brazil
  • Local Institution
  • Sao Paulo 01246-000 Brazil
  • Local Institution
  • St. John's Newfoundland and Labrador A1B 3V6 Canada
  • Local Institution
  • Toronto Ontario M4N 3M5 Canada
  • Local Institution
  • Toronto Ontario M5G 1X6 Canada
  • Local Institution
  • Sherbrooke Quebec J1H 5N4 Canada
  • Local Institution
  • Quebec G1R 2J6 Canada
  • Local Institution
  • Santiago Metropolitana Chile
  • Local Institution
  • Beijing Beijng 100021 China
  • Local Institution
  • Guangzhou Guangdong 510080 China
  • Local Institution
  • Nanjing Jiangsu 210008 China
  • Local Institution
  • Nanchang Jiangxi China
  • Local Institution
  • Shanghai Shanghai 200025 China
  • Local Institution
  • Shanghai Shanghai 200032 China
  • Local Institution
  • Shanghai Shanghai 200040 China
  • Local Institution
  • Shanghai Shanghai 200433 China
  • Local Institution
  • Hangzhou Zhejiang 310003 China
  • Local Institution
  • Beijing 100083 China
  • Local Institution
  • Beijing 100142 China
  • Local Institution
  • Angers 49100 France
  • Local Institution
  • Bordeaux 33000 France
  • Local Institution
  • LILLE Cedex 59037 France
  • Local Institution
  • Strasbourg Cedex 67091 France
  • Local Institution
  • Suresnes 92151 France
  • Local Institution
  • Hong Kong Hong Kong
  • IRCCS Istituto Nazionale Tumori Milano
  • Milano 20133 Italy
  • Local Institution
  • Modena 41100 Italy
  • Instituto Nazionale Tumori Fondazione G. Pascale
  • Napoli 80131 Italy
  • Azienda Ospedaliera Universitaria Pisana
  • Pisa 56126 Italy
  • Centro De Estudios Y Prevencion Del Cancer A. C.
  • Tuxtla Gutierrez Chiapas 290838 Mexico
  • Cryptex Investigacion Clinica Sa de Cv
  • Ciudad de Mexico Distrito Federal 06100 Mexico
  • Local Institution
  • Df Distrito Federal 06720 Mexico
  • Local Institution
  • Amsterdam 1066 CX Netherlands
  • Local Institution
  • Nijmegen 6525 GA Netherlands
  • Local Institution
  • Utrecht 3584CX Netherlands
  • Local Institution
  • Omsk 644013 Russian Federation
  • Local Institution
  • Saint-Petersburg 194044 Russian Federation
  • Local Institution
  • Barcelona 08025 Spain
  • Local Institution
  • Madrid 28041 Spain
  • Local Institution
  • Malaga 29010 Spain
  • Local Institution
  • Istanbul 34000 Turkey
  • Local Institution
  • Istanbul 34214 Turkey
  • Local Institution
  • Istanbul 34300 Turkey
  • Local Institution
  • Chelmsford Essex CM1 7ET United Kingdom
  • Local Institution
  • Southampton Hampshire SO16 6YD United Kingdom
  • Local Institution
  • Lancaster LA1 4RP United Kingdom
  • Local Institution
  • London N18 1QX United Kingdom
  • Local Institution
  • London NW1 2BU United Kingdom

View trial on ClinicalTrials.gov


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


Condition: Urinary Bladder Neoplasms

Intervention:

  • Drug: Durvalumab
  • Drug: Vicinium

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03258593

Sponsor: National Cancer Institute (NCI)

Primary Outcome Measures:

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

Estimated Enrollment: 40

Study Start Date: June 7, 2018

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed by NCI Laboratory of Pathology as high grade non-muscle invasive urothelial (transitional cell carcinoma) of the bladder as follows:
  • Carcinoma-in-situ (CIS) with or without papillary tumors
  • High-grade Ta or T1 disease based on a biopsy/TURBT performed within 12 weeks of the initial dose of study treatment. If multiple bladder biopsies/TURBTs are required to confirm eligibility, the timing of the last bladder biopsy to the initial dose of study treatment must be within 12 weeks.
  • Patients with persistent T1 high grade disease on TURBT following a single induction course of BCG (at least 5 of 6 doses) may also be eligible for this trial provided that the patient is surgically unfit for cystectomy as deemed by the investigator or the patient declines cystectomy.
  • Subjects with BCG unresponsive disease as defined by the Society of Urologic Oncology and the FDA: Subjects must have received at least two courses of intravesical BCG (at least 5 of 6 induction doses of BCG and at least 2 of 3 maintenance doses of BCG under a maintenance regimen or at least 2 doses of a repeat induction course). Please note exception above for persistent T1 disease. There is no upper limit on the amount of prior BCG a subject may have received.
  • Patients who have met eligibility criterion above must have received last BCG dose within a year of enrollment.
  • The investigator must document that he/she believes the subject would not benefit from additional BCG treatment at the time of study entry.
  • Age >= 18 years at time of signing the informed consent form (ICF). Because no dosing or adverse event data are currently available on the use of Vicinium in combination with durvalumab in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials. Furthermore, NMIBC does not occur in children.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Adequate normal 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.)
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • 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). Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • History of leptomeningeal carcinomatosis
  • Receipt of live attenuated vaccination within 30 days prior to the first dose of Vicinium or durvalumab
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Subjects with uncontrolled seizures
  • Any unresolved toxicity NCI CTCAE Grade >=2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
  • Subjects with Grade >=2 neuropathy will be evaluated on a case-by-case basis after consultation with the Principal Investigator.
  • Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Principal Investigator.

Contact:

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

Location:

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

View trial on ClinicalTrials.gov


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PhAse 1/2 StuDy of Modern ImmunotherApy in BCG-RelaPsing UroThelial Carcinoma of the BLADDER - (ADAPT-BLADDER) HCRN GU16-243


Condition: Urothelial Carcinoma, Bladder Cancer

Intervention:

  • Drug: Durvalumab
  • Radiation: External Beam Radiotherapy (EBRT)
  • Biological: Bacillus Calmette-Guérin (BCG)

Purpose: A multi-arm multi-stage (MAMS) phase 1/2 study. Phase 1 will be conducted in BCG-unresponsive NMIBC patients to establish the safety of durvalumab monotherapy (cohort 1) and durvalumab in combination with BCG (cohort 2a) and external beam radiation therapy (EBRT) (cohort 2b). Provided safety is demonstrated and recommended phase 2 doses (RP2D) are established in phase 1, the study will proceed to phase 2 testing. Phase 2 will be conducted in the BCG-relapsing NMIBC population. In phase 2, BCG-relapsing NMIBC subjects will be randomized between treatment arms examining intravesical BCG in combination with novel immunotherapy agents (durvalumab), novel immunotherapy in combination with radiation (durvalumab + EBRT), or retreatment with intravesical BCG. In addition to providing additional safety data on the combination regimens studied, phase 2 will provide preliminary efficacy profiles for BCG-relapsing NMIBC subjects with and without CIS treated with each regimen. For regimens demonstrating a tolerable safety profile and encouraging clinical activity in this phase 1/2 design, a randomized phase 3 trial of experimental arm therapy versus re-treatment with intravesical BCG therapy would be considered.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03317158

Sponsor: Noah Hahn, M.D.

Primary Outcome Measures:

  • Measure: Phase 1: Determine the recommended phase 2 dose (RP2D) of immunotherapy doublet combinations
  • Time Frame: 6 months
  • Safety Issue:
  • Measure: Phase 2: Determine the 6-month relapse-free survival (RFS) rates of BCG-relapsing non-muscle invasive bladder cancer (NMIBC) subjects treated with immunotherapy doublet combinations or BCG re-treatment
  • Time Frame: 6 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Phase 1: Characterize the 6-month relapse-free survival (RFS) rate of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) subjects treated with immunotherapy monotherapy or doublet combinations
  • Time Frame: 6 months
  • Safety Issue:
  • Measure: Assess the safety profile of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) subjects treated with immunotherapy monotherapy or doublet combinations by reporting the highest grade adverse event per patient, as assessed by CTCAE v4.0.
  • Time Frame: up to 24 months
  • Safety Issue:
  • Measure: Phase 2: Determine the 24-month relapse-free survival (RFS) rates of BCG-relapsing non-muscle invasive bladder cancer (NMIBC) subjects treated with immunotherapy doublet combinations or BCG re-treatment
  • Time Frame: up to 24 months
  • Safety Issue:
  • Measure: Phase 2: Identify significant associations between 6- and 24-month RFS rates and baseline tumor immunohistochemistry staining patterns of PD-L1 and other relevant mechanism of action targets for each drug studied within each study arm.
  • Time Frame: up to 24 months
  • Safety Issue:
  • Measure: Phase 2: Determine the 6-month relapse-free survival (RFS) rate of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) subjects treated with durvalumab
  • Time Frame: 6 months
  • Safety Issue:
  • Measure: Phase 2: Determine the 24-month relapse-free survival (RFS) rate of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) subjects treated with durvalumab.
  • Time Frame: up to 24 months
  • Safety Issue:
  • Measure: Assess the safety profile of BCG-relapsing non-muscle invasive bladder cancer subjects treated with immunotherapy monotherapy, doublet combinations or BCG re-treatment by reporting the highest grade adverse event per patient as assessed by CTCAE v4.0.
  • Time Frame: up to 24 months
  • Safety Issue:

Estimated Enrollment: 186

Study Start Date: November 21, 2017

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • (All Patients): Subject must meet all of the following applicable criteria to participate in this study:
  • Histologically confirmed non-muscle invasive urothelial carcinoma of the bladder (Ta, T1, or Tis stage) on TURBT obtained within 42 days of registration.
  • ECOG (WHO) performance status 0 or 1
  • Age ≥ 18 years old at time of consent
  • Adequate hematologic, hepatic, and renal function as defined by the following laboratory parameters:
  • White blood cell count (WBC) > 3.0 K/mm^3
  • Absolute neutrophil count (ANC) ≥ 1.5 K/mm^3
  • Platelets ≥ 100 K/mm^3
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Serum total bilirubin: ≤ 1.5 x ULN
  • ALT and AST ≤ 2.5 x ULN
  • Serum creatinine clearance (CrCl) ≥ 30 mL/min using the Cockcroft-Gault equation, see formula below:
  • CrCl = [140-age (years)] x weight (kg) / [72 x serum Cr (mg/dL)] (if subject is female multiply the above by 0.85)
  • Subjects who give a written informed consent obtained according to local guidelines. Inclusion Criteria (Phase 1 Only):
  • In addition to the inclusion criteria required of all patients listed above, the following inclusion criteria are also required of patients enrolling to Phase 1 of the study.
  • BCG-unresponsive disease defined by any of the following:
  • Prior treatment with 2 or more adequate courses of BCG (at least 5 of 6 induction installations and at least 2 of 3 maintenance installations for subjects on maintenance therapy)
  • Persistent T1 high-grade disease at the initial 3-month cystoscopy/TURBT assessment in subjects who received 5 of 6 inductions BCG installations
  • Relapsed NMIBC within 6 months of last exposure to BCG
  • Prostatic urethra involvement of NMIBC Inclusion Criteria (Phase 2 Only):
  • In addition to the inclusion criteria required of all patients listed above, the following inclusion criteria are also required of patients enrolling to Phase 2 of the study. Intermediate or high-risk NMIBC defined according to modified EORTC risk criteria summarized as follows:
  • Low-risk Tumors Initial or recurrent tumor > 12 months after resection with all of the following:
  • Solitary tumor
  • Low-grade
  • < 3 cm
  • No CIS
  • Intermediate-Risk Tumors: All tumors not defined in the two adjacent categories (between the category of low- and high-risk).
  • High-risk Tumors: Any of the following:
  • T1 tumor
  • High-grade
  • CIS
  • Multiple and recurrent and large (> 3 cm) Ta low-grade tumors (all conditions must be met for this point on Ta low-grade tumors).
  • Documented recurrence within 15 months of last exposure to intravesical therapy.
  • Recurrence after 1 prior induction course of intravesical BCG. Inclusion Criteria (Phase 2 Patients with Persistent or Relapsed NMIBC who Cross-Over to Durvalumab Only):
  • In addition to the inclusion criteria described of all patients listed above, the following inclusion criteria are also required of patients originally enrolled in Phase 2 of the study who are noted to have NMIBC in follow up and opt to cross-over to durvalumab monotherapy.
  • Subjects with BCG-unresponsive disease defined by any of the following:
  • Prior treatment with 2 or more adequate courses of BCG (at least 5 of 6 induction installations and at least 2 of 3 maintenance installations for subjects on maintenance therapy).
  • Persistent T1 high-grade disease at the initial 3-month cystoscopy/TURBT assessment in subjects who received 5 of 6 inductions BCG installations.
  • Relapsed NMIBC within 6 months of last exposure to BCG
  • Prostatic urethra involvement of NMIBC Primary Exclusion Criteria: Exclusion Criteria (All Patients):
  • Subjects with muscle-invasive (i.e. T2, T3, T4), locally advanced unresectable, or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 28 days prior to study registration. The required radiographic imaging includes:
  • Abdomen/Pelvis
  • CT scan
  • Chest
  • chest x-ray or CT scan
  • Subjects with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer. Subjects that have completed all necessary therapy and are considered to be at less than 30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment.
  • Subjects who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy.
  • 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:
  • Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the sponsor-investigator.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the sponsor-investigator.
  • Subjects who have received prior therapy with PD-1 or PD-L1 directed agents.
  • Subjects who have had any prior radiation to the prostate or pelvis.
  • Subjects who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or subjects who have had minor procedures (i.e. TURBT), percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury.
  • Subjects with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
  • Clinically significant cardiac diseases, including any of the following:
  • History or presence of serious uncontrolled ventricular arrhythmias.
  • Clinically significant resting bradycardia.
  • Any of the following within 3 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE).
  • Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s).
  • Cirrhosis
  • Active Infection (includes chronic active and chronic persistent).
  • Tuberculosis
  • Hepatitis B (known positive HBV surface antigen (HbsAg). 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.
  • Hepatitis C. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Known diagnosis of human immunodeficiency virus (HIV/positive HIV 1/2 antibodies) infection (HIV testing is not mandatory).
  • 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.
  • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. 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).
  • Usage of non-steroidal anti-inflammatory medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of gout are permitted.
  • Pregnant or breast-feeding women. Women of child-bearing potential must have a negative urine or serum test ≤ 14 days prior to starting study drug.
  • Women of child-bearing potential, who are biologically able to conceive, and not employing two forms of highly effective contraception or abstinence. Highly effective contraception or abstinence must be used from the time of informed consent, throughout the trial and up to 180 days after the last dose of durvalumab (e.g. male condom with spermicidal; diaphragm with spermicide; intra-uterine device). Women of child-bearing potential are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). 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 post-menopausal 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 radiation-induced 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).
  • Fertile males not willing to use contraception or abstinence, as stated above. Contraception or abstinence must be followed from screening through 180 days after receipt of the final dose of durvalumab therapy.
  • Subjects unwilling or unable to comply with the protocol.
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. Exclusion Criteria (Phase 1 Only):
  • In Phase 1 of the study, there are no additional exclusion criteria beyond those described of all patients in the section listed above. Exclusion Criteria (Phase 2 Only):
  • In addition to the exclusion criteria described of all patients listed above, the following exclusion criteria apply to patients enrolling to Phase 2 of the study.
  • Subjects with BCG-unresponsive disease defined by any of the following:
  • Prior treatment with 2 or more adequate courses of BCG (at least 5 of 6 induction installations and at least 2 of 3 maintenance installations for subjects on maintenance therapy).
  • Persistent T1 high-grade disease at the initial 3-month cystoscopy/TURBT assessment in subjects who received 5 of 6 inductions BCG installations.
  • Relapsed NMIBC within 6 months of last exposure to BCG.
  • Prostatic urethra involvement of NMIBC.
  • Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma. Exclusion Criteria (Phase 2 Patients with Persistent or Relapsed NMIBC who Cross-Over to Durvalumab Only):
  • In addition to the exclusion criteria described of all patients listed above, the following

Exclusion Criteria:

  • Exclusion Criteria (All Patients):
  • Subjects with muscle-invasive (i.e. T2, T3, T4), locally advanced unresectable, or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 28 days prior to study registration. The required radiographic imaging includes:
  • Abdomen/Pelvis
  • CT scan
  • Chest
  • chest x-ray or CT scan
  • Subjects with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer. Subjects that have completed all necessary therapy and are considered to be at less than 30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment.
  • Subjects who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy.
  • 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:
  • Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the sponsor-investigator.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the sponsor-investigator.
  • Subjects who have received prior therapy with PD-1 or PD-L1 directed agents.
  • Subjects who have had any prior radiation to the prostate or pelvis.
  • Subjects who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or subjects who have had minor procedures (i.e. TURBT), percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury.
  • Subjects with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
  • Clinically significant cardiac diseases, including any of the following:
  • History or presence of serious uncontrolled ventricular arrhythmias.
  • Clinically significant resting bradycardia.
  • Any of the following within 3 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE).
  • Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s).
  • Cirrhosis
  • Active Infection (includes chronic active and chronic persistent).
  • Tuberculosis
  • Hepatitis B (known positive HBV surface antigen (HbsAg). 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.
  • Hepatitis C. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Known diagnosis of human immunodeficiency virus (HIV/positive HIV 1/2 antibodies) infection (HIV testing is not mandatory).
  • 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.
  • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. 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).
  • Usage of non-steroidal anti-inflammatory medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of gout are permitted.
  • Pregnant or breast-feeding women. Women of child-bearing potential must have a negative urine or serum test ≤ 14 days prior to starting study drug.
  • Women of child-bearing potential, who are biologically able to conceive, and not employing two forms of highly effective contraception or abstinence. Highly effective contraception or abstinence must be used from the time of informed consent, throughout the trial and up to 180 days after the last dose of durvalumab (e.g. male condom with spermicidal; diaphragm with spermicide; intra-uterine device). Women of child-bearing potential are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). 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 post-menopausal 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 radiation-induced 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).
  • Fertile males not willing to use contraception or abstinence, as stated above. Contraception or abstinence must be followed from screening through 180 days after receipt of the final dose of durvalumab therapy.
  • Subjects unwilling or unable to comply with the protocol.
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. Exclusion Criteria (Phase 1 Only):
  • In Phase 1 of the study, there are no additional exclusion criteria beyond those described of all patients in the section listed above. Exclusion Criteria (Phase 2 Only):
  • In addition to the exclusion criteria described of all patients listed above, the following exclusion criteria apply to patients enrolling to Phase 2 of the study.
  • Subjects with BCG-unresponsive disease defined by any of the following:
  • Prior treatment with 2 or more adequate courses of BCG (at least 5 of 6 induction installations and at least 2 of 3 maintenance installations for subjects on maintenance therapy).
  • Persistent T1 high-grade disease at the initial 3-month cystoscopy/TURBT assessment in subjects who received 5 of 6 inductions BCG installations.
  • Relapsed NMIBC within 6 months of last exposure to BCG.
  • Prostatic urethra involvement of NMIBC.
  • Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma. Exclusion Criteria (Phase 2 Patients with Persistent or Relapsed NMIBC who Cross-Over to Durvalumab Only):
  • In addition to the exclusion criteria described of all patients listed above, the following exclusion criteria apply to patients enrolling to the cross-over to durvalumab portion of the Phase 2 study.
  • Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma.

Contact:

  • Ahran Lee
  • 317.634.5842 Ext. 14

Locations:

  • BCG Oncology
  • Phoenix Arizona 85032 United States
  • Indiana University Melvin and Bren Simon Cancer Center
  • Indianapolis Indiana 46202 United States
  • University of Iowa Hospitals and Clinics
  • Iowa City Iowa 52242 United States
  • Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center
  • Baltimore Maryland 21231 United States
  • Fox Chase Cancer Center
  • Philadelphia Pennsylvania 19111 United States

View trial on ClinicalTrials.gov


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A Single-arm, Open-label, Multicenter Study of Enfortumab Vedotin (ASG-22CE) for Treatment of Patients With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Immune Checkpoint Inhibitor (CPI) Therapy


Condition: Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Urologic Neoplasms, Renal Pelvis Neoplasms, Urothelial Cancer, Ureteral Neoplasms, Urethral Neoplasms

Intervention:

  • Drug: Enfortumab vedotin

Purpose: This is a study that will test how an experimental drug (enfortumab vedotin) affects patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other areas of the body. This clinical trial will enroll patients who were previously treated with a kind of anticancer drug called an immune checkpoint inhibitor (CPI). Some CPIs have been approved for the treatment of urothelial cancer. This study will test if the cancer shrinks with treatment. This study will also look at the side effects of the drug. A side effect is a response to a drug that is not part of the treatment effect. Patients who sign up for this trial must also fall into one of these categories: - Patients have already received treatment with platinum-containing chemotherapy - Patients have never received platinum-containing treatment and are not eligible for treatment with cisplatin.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03219333

Sponsor: Astellas Pharma Global Development, Inc.

Primary Outcome Measures:

  • Measure: Objective response rate (ORR) by an independent review facility (IRF)
  • Time Frame: Up to 3 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Duration of response (DOR) by an IRF
  • Time Frame: Up to 7.5 years
  • Safety Issue:
  • Measure: Disease control rate at 16 weeks (DCR16) by an IRF
  • Time Frame: 16 weeks
  • Safety Issue:
  • Measure: Progression free survival (PFS) by an IRF
  • Time Frame: Up to 7.5 years
  • Safety Issue:
  • Measure: ORR by investigator assessment
  • Time Frame: Up to 7.5 years
  • Safety Issue:
  • Measure: DOR by investigator assessment
  • Time Frame: Up to 7.5 years
  • Safety Issue:
  • Measure: DCR16 by investigator assessment
  • Time Frame: 16 weeks
  • Safety Issue:
  • Measure: Progression free survival (PFS) by investigator assessment
  • Time Frame: Up to 7.5 years
  • Safety Issue:
  • Measure: Overall survival (OS)
  • Time Frame: Up to 7.5 years
  • Safety Issue:
  • Measure: Incidence of adverse events (AEs)
  • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
  • Safety Issue:
  • Measure: Incidence of laboratory abnormalities
  • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
  • Safety Issue:
  • Measure: Pharmacokinetics (PK) parameter for enfortumab vedotin: Maximum concentration (Cmax)
  • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
  • Safety Issue:
  • Measure: PK parameter for enfortumab vedotin: Trough concentration (Ctrough)
  • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
  • Safety Issue:
  • Measure: PK parameter for monomethyl auristatin E (MMAE): Cmax
  • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
  • Safety Issue:
  • Measure: PK parameter for MMAE: Ctrough
  • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
  • Safety Issue:
  • Measure: PK parameter for Total Antibody (TAb): Cmax
  • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
  • Safety Issue:
  • Measure: PK parameter for Total Antibody (TAb): Ctrough
  • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
  • Safety Issue:
  • Measure: Incidence of antitherapeutic antibodies (ATA) to enfortumab vedotin
  • Time Frame: Through 1 month following last dose, or end-of-treatment visit whichever is later, up to 7.5 years
  • Safety Issue:

Estimated Enrollment: 200

Study Start Date: October 8, 2017

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Histologically documented urothelial carcinoma (squamous differentiation or mixed cell types allowed).
  • Metastatic disease or locally advanced disease that is not resectable.
  • Must have received prior treatment with a CPI in the locally advanced or metastatic urothelial cancer setting. A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. Patients who received CPI therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible.
  • Must either have prior treatment with platinum-containing chemotherapy (Cohort 1) or be platinum-naïve and ineligible for treatment with cisplatin at time of enrollment (Cohort 2).
  • Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy.
  • Tumor tissue samples must be available for submission to the sponsor prior to study treatment.
  • Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1).
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1 for Cohort 1 or ≤2 for Cohort 2.
  • Anticipated life expectancy of ≥3 months as assessed by the investigator.

Exclusion Criteria:

  • Ongoing sensory or motor neuropathy Grade ≥2.
  • Active central nervous system (CNS) metastases.
  • Immunotherapy related myocarditis, colitis, uveitis, or pneumonitis.
  • Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
  • Uncontrolled tumor-related pain or impending spinal cord compression.

Contact:

  • Seattle Genetics Trial Information Support
  • 866-333-7436

Locations:

  • Mayo Clinic Arizona
  • Scottsdale Arizona 85259 United States
  • Arizona Oncology Associates, PC - HOPE
  • Tucson Arizona 85710 United States
  • University of California Davis
  • Davis California 95616 United States
  • Keck Medical Center / University of Southern California
  • Los Angeles California 90033 United States
  • Keck Medical Center / Newport Beach
  • Newport Beach California 92663 United States
  • Kaiser Permanente Oakland
  • Oakland California 94611 United States
  • Chao Family Comprehensive Cancer Center University of California Irvine
  • Orange California 92868 United States
  • University of California Irvine - Newport
  • Orange California 92868 United States
  • Kaiser Permanente Roseville
  • Roseville California 95661 United States
  • Kaiser Permanente Sacramento
  • Sacramento California 95825 United States
  • Kaiser Permanente San Francisco
  • San Francisco California 94115 United States
  • Kaiser Permanente San Jose
  • San Jose California 95119 United States
  • Kaiser Permanente San Leandro
  • San Leandro California 94577 United States
  • Kaiser Permanente Santa Clara
  • Santa Clara California 95051 United States
  • Kaiser Permanente South San Francisco
  • South San Francisco California 94080 United States
  • Kaiser Permanente Medical Center Northern California
  • Vallejo California 94589 United States
  • Kaiser Permanente Walnut Creek
  • Walnut Creek California 94596 United States
  • Rocky Mountain Cancer Centers - Aurora
  • Aurora Colorado 80012 United States
  • Yale Cancer Center
  • New Haven Connecticut 06520 United States
  • Ocala Oncology Center
  • Ocala Florida 34471 United States
  • H. Lee Moffitt Cancer Center & Research Institute
  • Tampa Florida 33612 United States
  • University of Chicago
  • Chicago Illinois 60637-1470 United States
  • Norton Cancer Institute
  • Louisville Kentucky 40202 United States
  • Johns Hopkins Medical Center
  • Baltimore Maryland 21231 United States
  • Maryland Oncology Hematology, P.A.
  • Silver Spring Maryland 20904 United States
  • Massachusetts General Hospital
  • Boston Massachusetts 02114 United States
  • Dana Farber Cancer Institute
  • Boston Massachusetts 02215 United States
  • Karmanos Cancer Institute / Wayne State University
  • Detroit Michigan 48201 United States
  • Washington University School of Medicine
  • Saint Louis Missouri 63110 United States
  • Comprehensive Cancer Centers of Nevada
  • Las Vegas Nevada 89169 United States
  • New York Oncology Hematology, P.C.
  • Albany New York 12206 United States
  • New York University (NYU) Cancer Institute
  • New York New York 10016 United States
  • Columbia University Medical Center
  • New York New York 10022 United States
  • Mount Sinai Medical Center
  • New York New York 10029 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10087-9049 United States
  • James P. Wilmot Cancer Center / University of Rochester Medical Center
  • Rochester New York 14642 United States
  • Duke University Medical Center
  • Durham North Carolina 27710 United States
  • Cleveland Clinic, The
  • Cleveland Ohio 44195 United States
  • James Cancer Hospital / Ohio State University
  • Columbus Ohio 43210 United States
  • Northwest Cancer Specialists, P.C.
  • Tualatin Oregon 97062 United States
  • Thomas Jefferson University
  • Philadelphia Pennsylvania 19107 United States
  • Hillman Cancer Center / University of Pittsburgh Medical Center
  • Pittsburgh Pennsylvania 15232 United States
  • Greenville Health System Cancer Institute
  • Greenville South Carolina 29615 United States
  • Vanderbilt University Medical Center
  • Nashville Tennessee 37204 United States
  • Texas Oncology - Austin Central
  • Austin Texas 78731 United States
  • Texas Oncology - Baylor Sammons Cancer Center
  • Dallas Texas 75246 United States
  • Houston Methodist Cancer Center
  • Houston Texas 77030 United States
  • University of Virginia
  • Charlottesville Virginia 22908 United States
  • Virginia Cancer Specialists, PC
  • Fairfax Virginia 22031 United States
  • Virginia Oncology Associates
  • Norfolk Virginia 23502 United States
  • Seattle Cancer Care Alliance / University of Washington
  • Seattle Washington 98109-1023 United States
  • Site FR33001
  • Villejuif-Cedex-France France
  • Site DE49001
  • Tübingen Germany
  • Site IT39001
  • Milano Italy
  • Site IT39003
  • Terni Italy
  • Site JP81001
  • Hirosaki Aomori Japan
  • Site JP81004
  • Tsukuba Ibaraki Japan
  • Site JP81002
  • Morioka Iwate Japan
  • Site JP81008
  • Osakasayama Osaka Japan
  • Site JP81006
  • Shinjuku-ku Tokyo Japan
  • Site JP81009
  • Ube Yamaguchi Japan
  • Site JP81005
  • Chiba Japan
  • Site JP81011
  • Fukuoka Japan
  • Site JP81012
  • Fukuoka Japan
  • Site JP81003
  • Nigata Japan
  • Site JP81007
  • Osaka Japan
  • Site JP81010
  • Tokushima Japan
  • Site KR82005
  • Daejeon Korea, Republic of
  • Site KR82003
  • Seongnam-si Korea, Republic of
  • Site KR82001
  • Seoul Korea, Republic of
  • Site KR82002
  • Seoul Korea, Republic of
  • Site KR82004
  • Seoul Korea, Republic of
  • Site NL31001
  • Amsterdam Netherlands
  • Site ES34003
  • Santander Spain

View trial on ClinicalTrials.gov


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