Androgen Receptor Antagonist ARN-509 With or Without Abiraterone Acetate, Gonadotropin-Releasing Hormone Analog, and Prednisone in Treating Patients With High-Risk Prostate Cancer Undergoing Surgery

PRIMARY OBJECTIVES:

I. To evaluate the effect of neoadjuvant androgen receptor antagonist ARN-509 (apalutamide)
with or without abiraterone acetate, GnRH agonist, and prednisone on the feasibility of
performing nerve-sparing radical prostatectomy (RP) in men with high-risk prostate cancer
(PCa).

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive androgen receptor antagonist ARN-509 orally (PO) daily for 3 months.
Patients then undergo radical prostatectomy.

ARM II: Patients receive GnRH agonist subcutaneously (SC) on day 1, androgen receptor
antagonist ARN-509 PO daily PO for 4 times, abiraterone acetate PO daily for 4 times, and
prednisone PO daily for 3 months. Patients then undergo radical prostatectomy.

ARM III: Patients undergo radical prostatectomy.

After completion of study treatment, patients are followed up for 2 years.

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)