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

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.