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

NCT02949284 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: Pro20160000563NCI-2016-01496081603P30CA072720
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

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.

Conditions

Stage II Prostate Adenocarcinoma; Stage III Prostate Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  At 12 months

Secondary Outcomes (9)

• Change in tumor volume on pelvic MRI after neoadjuvant therapy

  Baseline to week 13

• 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

• Number of patients with positive surgical margins

  Up to 5 years

• Postoperative continence rate as determined by the American Urological Association Symptom Score (AUAss)

  Up to 24 months after surgery

Study Arms (3)

Arm I (androgen receptor ARN-509, radical prostatectomy)

EXPERIMENTAL

Patients receive androgen receptor antagonist ARN-509 PO daily for 3 months. Patients then undergo radical prostatectomy.

Drug: Androgen Receptor Antagonist ARN-509; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Radical Prostatectomy

Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)

ACTIVE COMPARATOR

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.

Drug: Abiraterone Acetate; Drug: Androgen Receptor Antagonist ARN-509; Biological: Gonadotropin-releasing Hormone Analog; Drug: Prednisone; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Radical Prostatectomy

Arm III (radical prostatectomy)

ACTIVE COMPARATOR

Patients undergo radical prostatectomy.

Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Radical Prostatectomy

Interventions

Abiraterone Acetate DRUG

Given PO

Also known as: CB7630, Zytiga

Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)

Androgen Receptor Antagonist ARN-509 DRUG

Given PO

Also known as: ARN-509

Arm I (androgen receptor ARN-509, radical prostatectomy); Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)

Gonadotropin-releasing Hormone Analog BIOLOGICAL

Given SC

Also known as: GnRH Agonist, GnRH Analog, Gonadotropin-Releasing Hormone Agonist, Gonadotropin-Releasing Hormone Analogue, LH-RH agonist, LH-RH Analogs, LHRH Agonist, luteinizing hormone-releasing hormone agonist, Luteinizing Hormone-Releasing Hormone Analog

Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisonum, Prednitone, Promifen, Servisone, SK-Prednisone

Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (androgen receptor ARN-509, radical prostatectomy); Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP); Arm III (radical prostatectomy)

Questionnaire Administration OTHER

Ancillary studies

Arm I (androgen receptor ARN-509, radical prostatectomy); Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP); Arm III (radical prostatectomy)

Radical Prostatectomy PROCEDURE

Undergo radical prostatectomy

Also known as: Prostatovesiculectomy

Arm I (androgen receptor ARN-509, radical prostatectomy); Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP); Arm III (radical prostatectomy)

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Yale Cancer Center

New Haven, Connecticut, 06519, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

MeSH Terms

Interventions

Abiraterone Acetate; apalutamide; Gonadotropin-Releasing Hormone; Prednisone; deltacortene; prednylidene

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Pregnadienediols; Pregnadienes; Pregnanes

Study Officials

• Saum Ghodoussipour, MD

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery, RWJMS

Study Record Dates

• First Submitted: October 21, 2016
• First Posted: October 31, 2016
• Study Start: June 20, 2017
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)