Pembrolizumab and BCG Solution in Treating Patients With Recurrent Non-Muscle-Invasive Bladder Cancer
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ClinicalTrials.gov Identifier: NCT02808143 |
Recruitment Status :
Active, not recruiting
First Posted : June 21, 2016
Last Update Posted : September 16, 2020
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Tracking Information | |||||
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First Submitted Date ICMJE | May 25, 2016 | ||||
First Posted Date ICMJE | June 21, 2016 | ||||
Last Update Posted Date | September 16, 2020 | ||||
Actual Study Start Date ICMJE | February 10, 2017 | ||||
Actual Primary Completion Date | May 15, 2020 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Maximum Tolerated Dose (MTD) [ Time Frame: Up to 9 weeks ] Determine the MTD of the study drug (MK-3475) when administered intravesically in combination with BCG in patients with high risk or BCG-refractory non-muscle-invasive bladder cancer (up to the individual maximum tolerated dose of each drug alone). The MTD will be defined as the highest dose that causes dose limiting toxicities (DLTs) in <2 of 6 patients graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
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Original Primary Outcome Measures ICMJE | Same as current | ||||
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Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures |
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Descriptive Information | |||||
Brief Title ICMJE | Pembrolizumab and BCG Solution in Treating Patients With Recurrent Non-Muscle-Invasive Bladder Cancer | ||||
Official Title ICMJE | 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 | ||||
Brief Summary | 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. | ||||
Detailed Description | PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of the study drug (pembrolizumab [MK-3475]) when administered intravesically in combination with BCG in patients with high risk or BCG-refractory non-muscle-invasive bladder cancer (up to the individual maximum tolerated dose of each drug alone). SECONDARY OBJECTIVES: I. To describe the dose limiting toxicities (DLTs) of MK-3475 in combination with BCG in this population. II. To assess the safety and tolerability of the combination of MK-3475 and BCG in subjects with high risk or BCG-refractory non-muscle-invasive bladder cancer. TERTIARY OBJECTIVES: I. To characterize the pharmacokinetics (PK) of MK-3475 in both blood and urine when administered intravesically in combination with BCG. II. To measure humoral and cellular responses to tumor antigens on serum and urine samples by measuring the levels of cytokines (ie, interleukin [IL]-2, IL-6, IL-8, IL-10, IL-18, interferon gamma [IFN-gamma] and tumor necrosis factor alpha [TNF-alpha]) and peripheral blood lymphocyte phenotype throughout treatment. III. To determine the response rate in terms of complete pathologic response in this population assessed when patient undergoes cystoscopies (weeks 17, 25, 33, 41, and 49 if applicable). IV. To document the progression rate associated with the combination of intravesical MK-3475 and BCG in patients with high risk or BCG-refractory non-muscle-invasive bladder cancer. V. To evaluate the relationship between tumor biomarkers programmed cell death (PD)-ligand (L)1, PD-L2, PD-1 as defined by immunohistochemistry (IHC) and adverse effects and recurrence rate. OUTLINE: This is a dose-escalation study of pembrolizumab. PRE-INDUCTION PHASE: Patients receive pembrolizumab intravesically once on day -14. INDUCTION PHASE: Patients receive BCG solution intravesically once weekly for 6 weeks at weeks 0-5 and pembrolizumab intravesically every 2 weeks at weeks 0, 2, and 4. MAINTENANCE PHASE: Beginning 2 weeks after the last dose of BCG solution, patients receive pembrolizumab intravesically every 2 weeks for 12 weeks at weeks 7, 9, 11, 13, 15, and 17 for a total of 6 doses. Patients then receive pembrolizumab intravesically every 4 weeks at weeks 21, 25, 29, 33, 37, 41, 45, and 49 for a total of 8 doses. After completion of study treatment, patients are followed up every 3 months for 2 years, every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 | ||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: Treatment (pembrolizumab, BCG solution)
PRE-INDUCTION PHASE: Patients receive pembrolizumab intravesically once on day -14. INDUCTION PHASE: Patients receive BCG solution intravesically once weekly for 6 weeks at weeks 0-5 and pembrolizumab intravesically every 2 weeks at weeks 0, 2, and 4. MAINTENANCE PHASE: Beginning 2 weeks after the last dose of BCG solution, patients receive pembrolizumab intravesically every 2 weeks for 12 weeks at weeks 7, 9, 11, 13, 15, and 17 for a total of 6 doses. Patients then receive pembrolizumab intravesically every 4 weeks at weeks 21, 25, 29, 33, 37, 41, 45, and 49 for a total of 8 doses. Interventions:
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Active, not recruiting | ||||
Actual Enrollment ICMJE |
9 | ||||
Original Estimated Enrollment ICMJE |
27 | ||||
Estimated Study Completion Date ICMJE | February 2022 | ||||
Actual Primary Completion Date | May 15, 2020 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT02808143 | ||||
Other Study ID Numbers ICMJE | NU 15U06 STU00202754 ( CTRP (Clinical Trial Reporting Program) ) NU 15U06 ( Other Identifier: Northwestern University ) P30CA060553 ( U.S. NIH Grant/Contract ) NCI-2016-00664 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) |
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Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Responsible Party | Joshua Meeks, Northwestern University | ||||
Study Sponsor ICMJE | Northwestern University | ||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Northwestern University | ||||
Verification Date | September 2020 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |