Phase 2 Study of Pembrolizumab in Combination With Gemcitabine and Cisplatin as Neoadjuvant Therapy

Bladder Cancer Clinical Trial

Official title: Phase II Single Arm Study of Gemcitabine and Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Prior to Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer

Status Active, not recruiting

Clinical Trial Summary

The purpose of this study is to evaluate whether adding pembrolizumab (Keytruda) to the combination of gemcitabine and cisplatin will improve shrinkage of the tumor before having a cystectomy, for people with muscle-invasive bladder cancer (MIBC).

Clinical Trial Description

Primary Objective To estimate the proportion of patients with pathological downstaging to <pT2 after neoadjuvant therapy with pembrolizumab in combination with gemcitabine and cisplatin in patients with MIBC

Hypothesis: The rate of pathologic downstaging to <pT2 will improve compared to historical controls

Secondary Objectives To estimate the proportion of patients with pT0 after neoadjuvant therapy with pembrolizumab when administered in combination with gemcitabine and cisplatin in patients with MIBC

Hypothesis: The rate of pathologic downstaging to pT0 will improve compared to historical controls

To estimate event free survival (EFS) Hypothesis: EFS will be improved compared to historical controls

To estimate overall survival (OS) Hypothesis: OS will be improved compared to historical controls

To estimate the proportion of patients who are alive at 3 years (OS at 3 years) Hypothesis:

OS at 3 years will be improved compared to historical controls

To characterize the toxicity profile for the combination of pembrolizumab, gemcitabine, and cisplatin Hypothesis: Pembrolizumab, gemcitabine, and cisplatin will be a safe combination with acceptable toxicity rates

Exploratory Objectives To explore the association of biological markers including PD-L1 expression and immune gene expression signatures with pathological downstaging to <pT2, pT0, EFS, and OS

To explore associations between BASE47 "basal," "claudin-low," and "luminal" subtypes of MIBC and pathological downstaging to <pT2, pT0, EFS, and OS

To characterize the change in phenotype of TILs, including delineation of effector and regulatory T cells, before and after neoadjuvant treatment

To define T cell receptor (TCR) and B cell receptor (BCR) repertoire profiles that are associated with pathological downstaging to <pT2, pT0, EFS, and OS

First the participant will receive all 3 study drugs (Pembrolizumab/Keytruda, gemcitabine and cisplatin) on the first day of a 3 week "cycle". The participant will then receive cisplatin and gemcitabine on the 8th day of the cycle.

The participant will receive the study drugs for 4 cycles for a total of 12 weeks.

Participants are followed for 5 years. ;

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

• NCT number: NCT02690558
• Study type: Interventional
• Source: UNC Lineberger Comprehensive Cancer Center
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 2016
• Completion date: January 30, 2026