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

Phase 2

Active, not recruiting

• Conditions: Stage II Prostate Adenocarcinoma; Stage III Prostate Adenocarcinoma
• Interventions: Drug: Abiraterone Acetate; Drug: Androgen Receptor Antagonist ARN-509; Other: Quality-of-Life Assessment; Biological: Gonadotropin-releasing Hormone Analog; Drug: Prednisone; Other: Questionnaire Administration; Procedure: Radical Prostatectomy

• Registration Number: NCT02949284
• Lead Sponsor: Rutgers, The State University of New Jersey

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2016-10-21
• Study First Submitted QC: 2016-10-27
• Study First Posted: 2016-10-31
• Study Start: 2017-06-20
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-24
• Last Update Posted: 2025-02-26
• Primary Completion: 2025-11-20
• Study Completion: 2026-11-20

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 90

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)	Androgen Receptor Antagonist ARN-509	Patients receive GnRH agonist 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 II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)	Gonadotropin-releasing Hormone Analog	Patients receive GnRH agonist 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 II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)	Questionnaire Administration	Patients receive GnRH agonist 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 II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)	Radical Prostatectomy	Patients receive GnRH agonist 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 (radical prostatectomy)	Questionnaire Administration	Patients undergo radical prostatectomy.
Arm I (androgen receptor ARN-509, radical prostatectomy)	Radical Prostatectomy	Patients receive androgen receptor antagonist ARN-509 PO daily for 3 months. Patients then undergo radical prostatectomy.
Arm III (radical prostatectomy)	Radical Prostatectomy	Patients undergo radical prostatectomy.
Arm I (androgen receptor ARN-509, radical prostatectomy)	Androgen Receptor Antagonist ARN-509	Patients receive androgen receptor antagonist ARN-509 PO daily for 3 months. Patients then undergo radical prostatectomy.
Arm I (androgen receptor ARN-509, radical prostatectomy)	Quality-of-Life Assessment	Patients receive androgen receptor antagonist ARN-509 PO daily for 3 months. Patients then undergo radical prostatectomy.
Arm I (androgen receptor ARN-509, radical prostatectomy)	Questionnaire Administration	Patients receive androgen receptor antagonist ARN-509 PO daily for 3 months. Patients then undergo radical prostatectomy.
Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)	Quality-of-Life Assessment	Patients receive GnRH agonist 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 (radical prostatectomy)	Quality-of-Life Assessment	Patients undergo radical prostatectomy.
Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)	Abiraterone Acetate	Patients receive GnRH agonist 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 II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)	Prednisone	Patients receive GnRH agonist 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.

Primary Outcome Measures

Name	Time	Method
Post-surgical potency rate defined as proportion of patients with International Index of Erectile Function score >= 17	At 12 months	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.

Secondary Outcome Measures

Name	Time	Method
Change in tumor volume on pelvic MRI after neoadjuvant therapy	Baseline to week 13	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.
Number of patients with positive surgical margins	Up to 5 years
Postoperative continence rate as determined by the Sexual Health Inventory for Men	Up to 24 months after surgery
Quality of life as assessed by the EPIC questionnaires	Up to 24 months after surgery
Quality of life as assessed by the AUAss questionnaires	Up to 24 months after surgery
Number of patients with biochemical recurrence defined using the Prostate Cancer Clinical Trials Working Group 2 definition	Up to 5 years
Number of patients with pathological T0	Up to 5 years
Postoperative continence rate as determined by the American Urological Association Symptom Score (AUAss)	Up to 24 months after surgery
Postoperative continence rate as determined by the Expanded Prostate Cancer Index Composite (EPIC)	Up to 24 months after surgery

Trial Locations

Locations (2)

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States