NCT02690558

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

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: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 39 (actual)
• Sponsor: UNC Lineberger Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

Detailed 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.

Conditions

• Bladder Cancer

Interventions

Type	Name	Description
DRUG	pembrolizumab, gemcitabine and cisplatin	neoadjuvant administration of pembrolizumab with gemcitabine and cisplatin prior to cystectomy

Timeline

• Start date: 2016-05-01
• Primary completion: 2020-07-06
• Completion: 2026-01-30
• First posted: 2016-02-24
• Last updated: 2026-03-20
• Results posted: 2021-08-10

Locations

2 sites across 1 country: United States