This randomized phase II trial studies how well androgen receptor antagonist ARN-509 works with or without abiraterone acetate, gonadotropin-releasing hormone agonist, and prednisone in treating patients with high-risk prostate cancer undergoing surgery. Androgen can cause the growth of prostate cancer cells. Hormone therapy using androgen receptor antagonist ARN-509, abiraterone acetate, and gonadotropin-releasing hormone analog (GnRH agonist) may fight prostate cancer by lowering the levels of androgen the body makes. Prednisone may either kill the tumor cells or stop them from dividing. Giving androgen receptor agonist ARN-509 with or without abiraterone acetate, GnRH agonist and prednisone may work better in treating patients with prostate cancer.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
90
Given PO
Given PO
Given SC
Given PO
Ancillary studies
Ancillary studies
Undergo radical prostatectomy
Yale Cancer Center
New Haven, Connecticut, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Post-surgical potency rate defined as proportion of patients with International Index of Erectile Function score >= 17
Each of the experimental arms will be compared to the surgery-only arm, so each test will be a 2.5% level one-sided test to control for the fact that there are two comparisons.
Time frame: At 12 months
Change in tumor volume on pelvic MRI after neoadjuvant therapy
Will be correlated with clinical outcomes before and after androgen receptor antagonist ARN-509 or androgen receptor antagonist ARN-509, GnRH agonist, prednisone plus abiraterone acetate.
Time frame: Baseline to week 13
Number of patients with biochemical recurrence defined using the Prostate Cancer Clinical Trials Working Group 2 definition
Time frame: Up to 5 years
Number of patients with pathological T0
Time frame: Up to 5 years
Number of patients with positive surgical margins
Time frame: Up to 5 years
Postoperative continence rate as determined by the American Urological Association Symptom Score (AUAss)
Time frame: Up to 24 months after surgery
Postoperative continence rate as determined by the Sexual Health Inventory for Men
Time frame: Up to 24 months after surgery
Postoperative continence rate as determined by the Expanded Prostate Cancer Index Composite (EPIC)
Time frame: Up to 24 months after surgery
Quality of life as assessed by the AUAss questionnaires
Time frame: Up to 24 months after surgery
Quality of life as assessed by the EPIC questionnaires
Time frame: Up to 24 months after surgery
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