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

Stage 0a Bladder Cancer AJCC v8 Clinical Trial

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

Status Recruiting

Clinical Trial Summary

This phase II trial studies the effect of adding pembrolizumab to gemcitabine in treating patients with non-muscle invasive bladder cancer whose cancer does not respond to Bacillus Calmette-Guerin (BCG) treatment. Chemotherapy drugs, such as gemcitabine, 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. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the patient's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Adding pembrolizumab to gemcitabine may delay the return of BCG-unresponsive bladder cancer for longer period compared to gemcitabine alone.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Estimate the 6-month complete response rate of treatment with intravesical gemcitabine hydrochloride (gemcitabine) in combination with MK-3475 (pembrolizumab) in patients with Bacillus Calmette-Guerin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) that have a carcinoma in situ (CIS) component.

II. Estimate the 18 month event-free survival (EFS) rate for all patients with BCG-unresponsive NMIBC receiving intravesical gemcitabine in combination with MK-3475 (pembrolizumab).

SECONDARY OBJECTIVES:

I. To characterize the safety profile of the combination of intravesical gemcitabine with MK-3475 (pembrolizumab) with BCG-unresponsive NMIBC (CIS or high grade Ta and T1 with or without a CIS component).

II. To estimate progression-free survival (PFS) of patients with BCG-unresponsive NMIBC treated with intravesical gemcitabine in combination with MK-3475 (pembrolizumab).

III. To estimate overall survival (OS) of patients with BCG-unresponsive NMIBC treated with intravesical gemcitabine in combination with MK-3475 (pembrolizumab).

IV. To estimate cystectomy-free survival of patients with BCG-unresponsive NMIBC treated with intravesical gemcitabine in combination with MK-3475 (pembrolizumab).

V. To estimate recurrence-free survival (RFS) for patients with a CIS component only and those without a CIS component.

EXPLORATORY OBJECTIVES:

I. To assess correlation between tumor mutation burden (TMB) and EFS and 6-month complete response (CR) rate.

II. To assess correlation between specific genomic alterations (single nucleotide variant [SNV] and copy number gains/loss) and EFS and 6-month complete response rate.

III. To assess correlation between APOBEC mutational signature and EFS and 6-month complete response rate.

IV. To assess correlation between immune gene signatures (IGS) and EFS and 6-month complete response rate.

V. To assess correlation between PD-L1 ribonucleic acid (RNA) levels and EFS and 6-month complete response rate.

VI. To assess correlation between RNA molecular subtype and EFS and 6-month complete response rate.

VII. To assess correlation between intratumoral T-cell receptor (TCR) clonality and EFS and 6-month complete response rate.

VIII. To assess correlation between changes in peripheral blood TCR clonality and EFS and 6-month complete response rate.

IX. To assess EFS in patients with urine cell free deoxyribonucleic acid (DNA) (cfDNA) + versus (vs.) patients with cfDNA.

OUTLINE:

INDUCTION: Patients receive pembrolizumab intravenously (IV) over 25-40 minutes on day 1 of cycles 1-4. 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.

After completion of study treatment, patients with evidence of disease (recurrence or progression) or stop study treatment to receive non-protocol treatment during induction are followed up every 6 months for 5 years. Patients who go off treatment due to any reason other than recurrence/progression or receiving subsequent non-protocol treatment during induction will go to clinical follow-up until evidence of disease progression/recurrence. Thereafter, patients are followed up every 6 months until 5 years from registration. Patients who complete scheduled maintenance treatment according to protocol therapy are followed up every 3 months for 2 years and then every 6 months for 3 years until disease progression/recurrence or receiving subsequent non-protocol treatment. Thereafter, patients are followed up every 6 months until 5 years from registration. Patients who have evidence of disease during maintenance therapy are followed up every 6 months until 5 years from registration. ;

Related Conditions & MeSH terms

• Bladder Urothelial Carcinoma In Situ
• Carcinoma
• Carcinoma in Situ
• Stage 0a Bladder Cancer AJCC v8
• Stage 0is Bladder Cancer AJCC v8
• Stage I Bladder Cancer AJCC v8
• Urinary Bladder Neoplasms

• NCT number: NCT04164082
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Recruiting
• Phase: Phase 2
• Start date: March 18, 2020
• Completion date: March 31, 2025