Androgen Deprivation Therapy and Apalutamide With or Without Radiation Therapy for the Treatment of Biochemically Recurrent Prostate Cancer, RESTART Study

PRIMARY OBJECTIVE: I. To assess PSA progression-free survival in both treatment arms. SECONDARY OBJECTIVES: I. To assess time of recovery of serum testosterone in both treatment arms. II. To assess PSA progression-free survival and overall survival following testosterone recovery in both treatment arms. III. To assess safety of androgen deprivation therapy (ADT) + apalutamide as well as ADT + apalutamide in combination radiation therapy. IV. To assess the time to first new metastasis or local / pelvic recurrence in both treatment arms. V. To assess the impact of both treatment arms on quality of life. VI. To assess the impact of both treatment arms on metabolic syndrome parameters. VII. To assess the impact of both treatment arms on bone density. VIII. To investigate the association of changes in repeat advanced imaging with outcome. IX. To compare fluciclovine and prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT). EXPLORATORY OBJECTIVE: I. To identify potential markers of response or resistance to the administered therapies. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive apalutamide orally (PO) once daily (QD) on days 1-28 and ADT consisting of leuprolide intramuscularly (IM) every 12 weeks or degarelix subcutaneously (SC) every 4 weeks. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. GROUP II: Patients receive apalutamide PO QD on days 1-28 and ADT consisting of leuprolide IM every 12 weeks or degarelix SC every 4 weeks. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy (RT) between cycles 4-7 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 and 4 months.