A Phase II Neoadjuvant Study of Apalutamide, Abiraterone Acetate, Prednisone, Degarelix and Indomethacin in Men With Localized Prostate Cancer Pre-prostatectomy

PRIMARY OBJECTIVES: I. The rate of the pathologic complete response (pCR) (i.e. no evidence of residual tumor) as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin. SECONDARY OBJECTIVES: I. To determine the negative margin rate as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin. II. To determine the rate of near pCR (i.e. =\< 5 mm of residual tumor) as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin. III. To determine the rate of pathologic T3 disease as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin. IV. To determine the rate of nodal metastases as assessed on surgical lymph node specimens following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin. V. To determine the apoptotic index (i.e. percentage of tumor cells undergoing apoptosis) as determined by cleaved caspase-3 immunohistochemistry following 3-months (12 weeks) of neoadjuvant apalutamide, abiraterone acetate, degarelix and indomethacin. VI. To determine the proportion of men who receive adjuvant radiation therapy within 1-year of prostatectomy. VII. To determine the biochemical (i.e. prostate-specific antigen \[PSA\]) progression free survival estimate two years after the last patient has accrued (i.e. confirmed PSA post-radical prostatectomy \>= 0.2 ng/mL). VIII. To determine the overall survival estimate two years after the last patient has accrued. IX. Safety as assessed by the incidence and severity of adverse events and serious adverse events graded according to the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. X. Exploratory biomarker assessment. OUTLINE: Patients receive apalutamide and abiraterone acetate orally (PO) daily, prednisone PO twice per day (BID) and indomethacin PO three times per day (TID). Patients also receive degarelix subcutaneously (SC) on day 1 and every 4 weeks for 3 doses. Treatment continues for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo prostatectomy on day 85. After completion of study treatment, patients are followed up at 28, 113, 450 and 815 days.