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Phase 2 Study of Pembrolizumab in Combination With Gemcitabine and Cisplatin as Neoadjuvant Therapy | Clinical Trials | Clareo Health

COMPLETEDPHASE2

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

NCT02690558•UNC Lineberger Comprehensive Cancer Center

View on ClinicalTrials.gov

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Be able to give written IRB approved informed consent and be able to follow protocol requirements.
•Be greater than or equal to 18 years of age on day of signing informed consent.
•Has a performance status of 0 or 1 on the ECOG Performance Scale
•Has histologically confirmed urothelial carcinoma of the bladder; those with mixed histology, including a component of urothelial carcinoma, are eligible. Pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded.
•Has clinical stage T2-T4a N0/X M0 urothelial carcinoma. Clinical T stage is based on the pre-study standard of care transurethral resection of the bladder tumor (TURBT) sample and imaging studies.
•Has staging scans with abdominal/pelvic CT or MRI scan and CT scan or x-ray of the chest within 4 weeks prior to treatment initiation
•Be a medically appropriate candidate for radical cystectomy as determined by an attending urologist and be planning to receive cystectomy.
•Has had no prior systemic cytotoxic chemotherapy for urothelial carcinoma (prior intravesicular chemotherapies are permitted)
•Patients must have tumor tissue from transurethral resection of the bladder tumor (TURBT) available for submission that is sufficient for correlative testing, and agree to submission of a paraffin block or 20 formalin-fixed paraffin embedded (FFPE) slides of 5-10 microns in thickness. Patients must also agree to submission of tissue from cystectomy.
•Demonstrate adequate organ function as defined in the table below; all screening labs should be performed within 10 days of treatment initiation.
+9 more criteria

Exclusion Criteria

•The subject must be excluded from participating in the trial if the subject meets any of the following:
•Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of pembrolizumab.
•Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. NOTE: see exception to use of systemic steroid as prophylactic anti-emetic prior to cisplatin in section 4.2.2. Inhaled and topical steroids are allowed.
•Has a known history of active TB (Bacillus Tuberculosis)
•Hypersensitivity to pembrolizumab or any of its excipients.
•Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
•Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
•• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
•Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
•Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
+11 more criteria

Locations (2)

North Carolina Cancer Hospital (UNC)

Chapel Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Key Dates

Start Date

May 1, 2016

Primary Completion Date

July 6, 2020

Completion Date

January 30, 2026

Last Updated

March 20, 2026

Enrollment

ACTUAL participants

Conditions

Bladder Cancer

Interventions

pembrolizumab, gemcitabine and cisplatin

DRUG

En-bloc Transurethral Resection of Bladder Tumor (En-bloc TURBT) Specimens Using a Redesigned Surgical Resectoscope Device

NCT04235764

Bladder Cancer

View study

RECRUITINGPHASE2

Combining Immunotherapy and Radiation Therapy to Help Patients Avoid Bladder Removal After Treatment Shrinks Muscle Invasive Bladder Cancer, BRIGHT Trial

NCT07061964

Muscle Invasive Bladder Urothelial CarcinomaStage II Bladder Cancer AJCC v8+1 more

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 20, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

En-bloc Transurethral Resection of Bladder Tumor (En-bloc TURBT) Specimens Using a Redesigned Surgical Resectoscope Device

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