LHRH Analogue Therapy With Enzalutamide or Bicalutamide in Treating Patients With Hormone Sensitive Prostate Cancer

PRIMARY OBJECTIVES: I. To compare the rates of achieving prostate-specific antigen (PSA) remission at month 7 with LHRH analogue therapy and enzalutamide (Arm A) with that achieved with LHRH analogue and bicalutamide (Arm B) in metastatic hormone sensitive prostate cancer. SECONDARY OBJECTIVES: I. To compare the primary endpoint by race. II. To compare the rates of each of 2 types of response by treatment arm: measurable disease response; and PSA response. III. To compare each of 7 time-to-event endpoints by treatment arm: duration of overall response (RD); duration of stable disease (SDD); time to treatment failure (TTF); time-to-progression (TTP); TTP in patients with bone metastases; progression-free survival (PFS); and overall survival (OS). IV. To compare the rates of each type of toxicity by treatment arm. V. To compare the incidence rate of skeletal related events (SRE), and the time until SRE, separately by treatment arm. VI. To compare the rates of circulating tumor cell (CTC) response by treatment arm. VIII. To explore the molecular mechanisms within the androgen receptor pathway by determining the levels of chemokine (C-X-C motif) receptor 4 (CXCR4) and transmembrane protease, serine 2 (TMPRSS2)-v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) expression, androgen metabolism enzymes; androgen receptor variants, and length of cytosine-adenine-guanine (CAG) repeats within the androgen receptor gene, and to associate them with the primary endpoint. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive enzalutamide orally (PO) once daily (QD) and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other Food and Drug Administration \[FDA\] approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.