NCT03978624

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

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
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: UNC Lineberger Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

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).

Detailed 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. 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 previous reported results of the trial which includes pembrolizumab and entinostat treatment in melanoma 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 the standard of care procedures.

Conditions

• Bladder Cancer

Interventions

Type	Name	Description
DRUG	Pembrolizumab	200 mg IV on day 1 and day 22
DRUG	Entinostat	5 mg given orally on day 1, day 8 and day 15
PROCEDURE	Procedure/Surgery	A radical cystectomy is a surgical procedure to remove the entire urinary bladder and maximal transurethral resection of bladder tumor (TURBT) is a surgical procedure used to remove as much of the bladder tumor as possible.

Timeline

• Start date: 2020-09-23
• Primary completion: 2024-03-25
• Completion: 2026-11-22
• First posted: 2019-06-07
• Last updated: 2025-10-15
• Results posted: 2025-10-07

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study