External Beam Radiation Therapy and Brachytherapy With Chemotherapy and Immunotherapy for the Treatment of Stage IVB Cervical Cancer

PRIMARY OBJECTIVE: I. To demonstrate that radiotherapy can be safely integrated into chemotherapy and pembrolizumab with bevacizumab in newly diagnosed stage IVB cervical cancer to improve outcomes. SECONDARY OBJECTIVE: I. To demonstrate improvements with overall response rate, overall survival (OS), and duration of response with the addition of radiation therapy to standard of care in stage IVB cervical cancer. EXPLORATORY OBJECTIVES: I. To demonstrate improved quality of life and disease-related toxicity with the addition of radiation therapy to standard of care chemotherapy in stage IVB cervical cancer. II. To explore the association of known risk factors (age, race/ethnicity, smoking status, baseline quality of life, combined positive score \[CPS\] score 1-10 versus \> 10, and performance status with the change in QOL, treatment outcomes, and toxicities. III. To explore circulating tumor deoxyribonucleic acid (ctDNA) as a biomarker to monitor the response to upfront chemotherapy-immunotherapy and subsequent radiation. IV. To use T cell receptor repertoire sequencing (TCRseq) to define T cell clones present in the tumor and to establish their concordance with peripheral blood T cell clones at baseline and in response to therapy. OUTLINE: PART 1: Patients receive cisplatin intravenously (IV), paclitaxel IV, pembrolizumab IV over 30 minutes, and bevacizumab IV on day 1 of each cycle. Cycles repeat every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive no treatment for 3 weeks. PART 2: Patients undergo EBRT for 25 treatments delivered over 5 weeks, and brachytherapy over 3-5 treatments. Patients also receive pembrolizumab IV over 30 minutes and bevacizumab IV on day 1 of each cycle. Cycles for immunotherapy repeat every 21 days for a total of 2 years in the absence of disease progression or unacceptable toxicity. Participants who complete study intervention after 2 years of pembrolizumab are eligible for up to 1 year of additional pembrolizumab (second course) upon experiencing disease progression. Patients undergo computed tomography (CT), positron emission tomography (PET)/CT, and/or magnetic resonance imaging (MRI) throughout the study. Patients also undergo blood sample collection throughout the study. After completion of study treatment, patients follow up at 30 days and every 6 weeks for up to 1 year then every 9 weeks.