Testing the Addition of an Anti-cancer Drug, Pembrolizumab, to the Usual Intravesical Chemotherapy Treatment (Gemcitabine) for the Treatment of BCG-Unresponsive Non-muscle Invasive Bladder Cancer
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|ClinicalTrials.gov Identifier: NCT04164082|
Recruitment Status : Recruiting
First Posted : November 15, 2019
Last Update Posted : February 19, 2020
|Condition or disease||Intervention/treatment||Phase|
|Bladder Urothelial Carcinoma In Situ High Risk Non-Muscle Invasive Bladder Urothelial Carcinoma Infiltrating Bladder Mixed Carcinoma Stage 0a Bladder Cancer AJCC v8 Stage 0is Bladder Cancer AJCC v8 Stage I Bladder Cancer AJCC v8||Drug: Gemcitabine Drug: Gemcitabine Hydrochloride Biological: Pembrolizumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||72 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Intravesical Gemcitabine and MK-3475 (Pembrolizumab) in the Treatment of Patients With BCG-Unresponsive Non-Muscle Invasive Bladder Cancer|
|Actual Study Start Date :||January 6, 2020|
|Estimated Primary Completion Date :||March 31, 2023|
|Estimated Study Completion Date :||March 31, 2023|
Experimental: Treatment (pembrolizumab, gemcitabine hydrochloride)
INDUCTION: Patients receive pembrolizumab IV over 25-40 minutes on day 1 of cycles 1 and 4. Patients also receive gemcitabine hydrochloride intravesically on days 1, 8 and 15 of cycles 1 and 2. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Beginning cycle 5, patients with no evidence of disease after induction receive pembrolizumab IV over 25-40 minutes and gemcitabine intravesically on day 1. Treatment repeats every 3 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Gemcitabine Hydrochloride
- Complete response rate in the carcinoma in situ (CIS) subpopulation [ Time Frame: At 6 months ]A complete response, only for patients with a CIS component, is a cystoscopy without evidence of bladder tumor, negative biopsy (including directed biopsies to any suspicious areas and in addition random bladder biopsies including trigone, left lateral wall, right lateral wall, posterior bladder, dome of bladder, and the prostatic urethra in men) and negative cytology for high grade disease at 6 months (end of cycle 8, week 25).
- Event-free survival at 18 months [ Time Frame: From the date of study registration to the first documentation of an event or death whichever comes first, assessed up to 18 months ]EFS will be measure from the date of study registration to the first documentation of an event or death whichever comes first. For patients without a documented event and who are still alive, they will be censored at last disease assessment. For patients who start any subsequent ant-cancer therapy without any reported events will be censored at their last disease assessment. will be obtained with a Kaplan-Meier estimator (using the Greenwood formula to estimate the variance) for the entire 155 patient group consisting of patients with CIS, CIS with Ta/T1 or Ta or T1 disease. A 90% confidence interval will be generated for the 18-month EFS estimate.
- Incidence of adverse events [ Time Frame: Up to 5 years post treatment ]Adverse events will be assessed based on the National Cancer Institute (NCI) common toxicity criteria (Common Terminology Criteria for Adverse Events [CTACAE] version [v] 5.0).
- Duration of response (DOR) [ Time Frame: From the time a patient had a documented response that had been confirmed (the time would start at the time a response was first noted) until disease-progression, assessed up to 5 years ]Analysis will only include those patients with a confirmed response. Patients who are alive and without a documented progression at the time of analysis will be censored at the time of the last disease status evaluation. The Kaplan-Meier product-limit estimator will be used to estimate DOR, medians and 95% confidence intervals (CI).
- Progression-free survival (PFS) [ Time Frame: From the date of study registration to the date of progression or death due to any cause, whichever occurs first, assessed up to 5 years ]Surviving patients without any documented progressions will be censored at the date of last known contact. Progression will be defined as the development of muscle invasive bladder cancer or metastatic urothelial cancer (nodal and/or distant). The Kaplan-Meier product-limit estimator will be used to estimate PFS, medians and 95% CI.
- Overall survival (OS) [ Time Frame: From the date of study registration to date of death due to any cause, assessed up to 5 years ]Surviving patients will be censored at the date of last known contact. The Kaplan-Meier product-limit estimator will be used to estimate OS, medians and 95% CI.
- Cystectomy-free survival [ Time Frame: From the date of study registration to the date of cystectomy for all patients ]The Kaplan-Meier product-limit estimator will be used to estimate cystectomy-free survival, medians and 95% CI.
- Recurrence free survival (RFS) [ Time Frame: From the date of study registration to the first documentation of recurrence or death due to any cause, assessed up to 5 years ]Surviving patients without any documented recurrence will be censored at the date of last known contact. Recurrence will be defined as the development of high-grade bladder cancer for patients with a CIS component only and those without a CIS component. The Kaplan-Meier product-limit estimator will be used to estimate RFS, medians and 95% CI.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04164082
|Principal Investigator:||Michael E Woods||Alliance for Clinical Trials in Oncology|