Randomized Three-Arm Trial to Evaluate the Effect of Neoadjuvant Apalutamide Alone or in Combination with Abiraterone Acetate and GnRH Agonist on Enhancing Surgical Outcome of Nerve-Sparing Radical Prostatectomy in Men with High-Risk Prostate Cancer.

Inclusion Criteria

- Histologically proven adenocarcinoma of the prostate and: Gleason > 8 OR prostatic

specific antigen (PSA) > 20 and more than 1 positive core

- Patients with Eastern Cooperative Oncology Group performance scale (ECOG PS) 0 or 1

- Clinical stage T3 or less as demonstrated by abdominal/pelvic computed tomography (CT)

or magnetic resonance imaging (MRI) will be selected as the prostate is resectable

- Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors within 3

months prior to randomization

- Platelet count >= 100,000 x 10^9/uL independent of transfusion and/or growth factors

within 3 months prior to randomization

- Serum albumin >= 3.0 g/dL

- Glomerular filtration rate (GFR) >= 45 mL/min

- Serum potassium >= 3.5 mmol/L

- Serum total bilirubin =< 1.5 × upper limit of normal (ULN) (Note: In subjects with

Gilbert's syndrome, if total bilirubin is > 1.5 × ULN, measure direct and indirect

bilirubin and if direct bilirubin is =< 1.5 × ULN, subject may be eligible)

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 × ULN

- Medications known to lower the seizure threshold must be discontinued or substituted

at least 4 weeks prior to study entry

- Agrees to use a condom (even men with vasectomies) and another effective method of

birth control if he is having sex with a woman of childbearing potential or agrees to

use a condom if he is having sex with a woman who is pregnant while on study drug and

for 3 months following the last dose of study drug; must also agree not to donate

sperm during the study and for 3 months after receiving the last dose of study drug

Exclusion Criteria

- Clinical stage T4 (invasion into rectum or ureters) significantly increases the

morbidity of the surgery

- Patients with rectal or ureteral invasion will be considered to have unresectable

disease

- History of any of the following:

- Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke

within 1year to randomization, brain arteriovenous malformation, Schwannoma,

meningioma, or other benign central nervous system [CNS] or meningeal disease

which may require treatment with surgery or radiation therapy)

- Severe or unstable angina, myocardial infarction, symptomatic congestive heart

failure, arterial within 6 months prior to randomization

- Venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident

including transient ischemic attacks) within 6 months prior to randomization

- Clinically significant ventricular arrhythmias within 6 months prior to

randomization

- Metastatic prostate cancer

- Baseline moderate or severe hepatic impairment (Child-Pugh class B or C)