Window of Opportunity Study of Pembrolizumab Alone and in Combinations in Bladder Cancer

Bladder Cancer Clinical Trial

Official title: Window of Opportunity Platform Study to Define Immunogenomic Changes With Pembrolizumab Alone and in Rational Combinations in Muscle-Invasive Bladder Cancer

Status Active, not recruiting

Clinical Trial Summary

This is an open-label, window of opportunity platform study for subjects with muscle-invasive bladder cancer (MIBC) who are deemed ineligible or refuse cisplatin-based neoadjuvant chemotherapy and are scheduled to undergo definitive surgery (radical cystectomy), or are planning to undergo trimodality therapy (maximal transurethral resection of the bladder tumor followed by concurrent chemoradiation).

The primary objective of this study is to assess changes to immunogenomic markers after treatment with pembrolizumab alone and in combination with the selective class I histone deacetylase (HDAC) inhibitor (entinostat).

Clinical Trial Description

The study will enroll 20 subjects with a confirmed diagnosis of MIBC (cT2-T4aN0M0) who are planned for definitive therapy with either radical cystectomy without cisplatin-based neoadjuvant chemotherapy or trimodality therapy. Subjects who are planned to undergo radical cystectomy must be deemed ineligible for (based on consensus criteria) [1] or refuse neoadjuvant cisplatin-based chemotherapy. Prior to study entry, subjects must consent to having tissue collected for research purposes during the scheduled cystectomy or maximal TURBT. After screening and enrollment, baseline blood and archived transurethral resection of the bladder tumor (TURBT) tumor tissue will be collected from each subject for baseline analyses. Subjects will then start on clinical trial treatment followed by either radical cystectomy or maximal TURBT followed by chemoradiation.

Blood and tumor will be collected from each subject at the time of cystectomy or maximal TURBT. The investigators do not anticipate delays in surgery due to the planned schedule of the preoperative treatment administration for the purposes of this study and based on the phase II ENCORE 601 trial (pembrolizumab and entinostat in melanoma) which reported an acceptable safety profile. Phase I data identified grade 1/2 fatigue as the most common entinostat-related toxicity, with neutropenia and anemia only occurring at doses exceeding those proposed for this study. Safety stopping rules for drug-related toxicity will dictate whether the trial should be halted if subjects are experiencing drug-related toxicity that delays or interferes with standard of care procedures. ;

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

• NCT number: NCT03978624
• Study type: Interventional
• Source: UNC Lineberger Comprehensive Cancer Center
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 23, 2020
• Completion date: November 22, 2026