Pembrolizumab and BCG Solution in Treating Patients With Recurrent Non-Muscle-Invasive Bladder Cancer

Recurrent Bladder Carcinoma Clinical Trial

Official title: 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

Status Active, not recruiting

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Recurrent Bladder Carcinoma
• Stage 0a Bladder Urothelial Carcinoma
• Stage 0is Bladder Urothelial Carcinoma
• Stage I Bladder Cancer
• Urinary Bladder Neoplasms

• NCT number: NCT02808143
• Study type: Interventional
• Source: Northwestern University
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 10, 2017
• Completion date: February 2023