Relugolix in Combination With Radiation Therapy for Treating Patients With High Risk Prostate Cancer

PRIMARY OBJECTIVE: I. To compare the biochemical recurrence rate between 12 and 24 months of relugolix in patients with high risk prostate cancer treated with combination external beam radiation and brachytherapy. SECONDARY OBJECTIVES: I. To compare the composite quality of life in patient treated with 12 months and 24 months of relugolix as assessed by the Expanded Prostate Composite Index Short Form (EPIC-26) instrument. II. To compare the treatment related toxicity between 12 months and 24 months of relugolix as assessed by Common Terminology Criteria for Adverse Events version 5.0. (CTCAE v 5.0) criteria. III. To compare the rate of major adverse cardiovascular events (MACE) in patients treated with 12 and 24 months of relugolix. IV. To establish the rate of patient compliance using patient reported drug diary. V. To compare the rate of testosterone recovery after 12 and 24 months of relugolix. EXPLORATORY OBJECTIVE: I. To establish Decipher genomic classifier as predictor of cancer control. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive relugolix orally (PO) once daily (QD). Cycles repeat every 3 months for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 30 to 180 days after start of relugolix, patients undergo brachytherapy and external beam radiation over 25 fractions. Patients undergo bone scan, computed tomography (CT) or magnetic resonance imaging (MRI) or prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scan during screening. Patients also undergo dual x-ray absorptiometry (DEXA) scan and may optionally undergo blood sample collection throughout the trial. ARM B: Patients receive relugolix PO QD. Cycles repeat every 3 months for 24 months in the absence of disease progression or unacceptable toxicity. Beginning 30 to 180 days after start of relugolix, patients undergo brachytherapy and external beam radiation over 25 fractions. Patients undergo bone scan, CT or MRI or PSMA PET scan during screening. Patients also undergo DEXA scan and may optionally undergo blood sample collection throughout the trial. After completion of study treatment, patients in Arm A are followed up every 3 months for 12 months and then every 6 months for up to 36 months and patients in Arm B are followed up every 6 months for up 36 months.