Ignite Creation Date:
2025-12-25 @ 12:22 AM
Ignite Modification Date:
2025-12-25 @ 10:26 PM
Study NCT ID:
NCT02690558
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-02-10
First Post:
2016-02-12
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Phase 2 Study of Pembrolizumab in Combination With Gemcitabine and Cisplatin as Neoadjuvant Therapy
Sponsor:
UNC Lineberger Comprehensive Cancer Center
Organization:
Study Overview
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
Status Verified Date:
2025-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: