NCT06770582

Testing the Addition of the Immunotherapy Drug, Pembrolizumab, to Radiation Therapy Compared to the Usual Chemotherapy Treatment During Radiation Therapy for Bladder Cancer, PARRC Trial

Randomized Phase II Trial of Pembrolizumab and Radiation vs. Radiation and Concurrent Chemotherapy for High-Grade T1 Bladder Cancer (PARRC Trial)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 160 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial compares the use of pembrolizumab and radiation therapy to chemotherapy with cisplatin, gemcitabine, 5-fluorouracil or mitomycin-C and radiation therapy for the treatment of non-muscle invasive bladder cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as cisplatin, gemcitabine, 5-fluorouracil or mitomycin-C, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving pembrolizumab with radiation may kill more tumor cells than chemotherapy with radiation therapy in patients with non-muscle invasive bladder cancer.

Detailed description

PRIMARY OBJECTIVE: I. To compare bladder-intact event-free survival. SECONDARY OBJECTIVES: I. To assess complete response by cystoscopy at 6 months. II. To assess disease-free survival. III. To assess local-regional control. IV. To assess metastasis-free survival. V. To assess overall survival. VI. To assess quality of life using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and the Bladder Cancer Index at 18 months. VII. To assess Common Terminology Criteria for Adverse Events (CTCAE) adverse events (both acute and late). EXPLORATORY OBJECTIVES: I. To assess fatigue using the Patient Reported Outcomes Measurement Information System Fatigue-4A (PROMIS-Fatigue-4a). II. To assess quality adjusted survival using European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L). III. To assess cumulative quality of life using EORTC QLC-C30 and Bladder Cancer Index at 24 months. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive one of the following chemotherapy regimens per physicians choice: 1) cisplatin intravenously (IV) once per week for 4 weeks, 2) gemcitabine IV on days 1, 4, 8, 11, 15, 18, 22, and 25, or 3) mitomycin IV on day 1 and 5-fluorouracil IV continuously over 120 hours on days 1-5 and 16-20. Patients receiving cisplatin or gemcitabine continue chemotherapy for 6 weeks if they are receiving radiation according to the standard hypofractionated radiation schedule. Starting on day 1, patients also receive radiation therapy for 20, 32, or 36 treatments over 4-7 weeks. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT)/magnetic resonance imaging (MRI) and blood sample collection throughout the study. Patients may also undergo optional urine sample collection on study. ARM 2: Patients receive pembrolizumab IV over 25-40 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for 9 cycles in the absence of disease progression or unacceptable toxicity. Starting on day 1, patients also receive radiation therapy for 20, 32, or 36 treatments over 4-7 weeks. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients also undergo CT/MRI and blood sample collection throughout the study. Patients may also undergo optional urine sample collection on study. After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years and then annually for 5 years.

Conditions

• Non-Muscle Invasive Bladder Urothelial Carcinoma
• Recurrent Non-Muscle Invasive Bladder Urothelial Carcinoma
• Stage I Bladder Cancer AJCC v8

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood and urine sample collection
DRUG	Cisplatin	Given IV
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Fluorouracil	Given IV
DRUG	Gemcitabine	Given IV
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
DRUG	Mitomycin	Given IV
BIOLOGICAL	Pembrolizumab	Given IV
OTHER	Questionnaire Administration	Ancillary studies
RADIATION	Radiation Therapy	Undergo radiation therapy

Timeline

• Start date: 2025-06-03
• Primary completion: 2032-02-01
• Completion: 2032-02-01
• First posted: 2025-01-13
• Last updated: 2026-04-15

Locations

123 sites across 1 country: United States

Regulatory

• FDA-regulated drug study