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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Stage II Prostate Adenocarcinoma; Stage III Prostate Adenocarcinoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Prednisone; Drug: Abiraterone Acetate; Procedure: Radical Prostatectomy; Drug: Androgen Receptor Antagonist ARN-509; Biological: Gonadotropin-releasing Hormone Analog

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 Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale Cancer Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (androgen receptor ARN-509, radical prostatectomy); Patients receive androgen receptor antagonist ARN-509 PO daily for 3 months. Patients then undergo radical prostatectomy.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Radical Prostatectomy; Undergo radical prostatectomy; Other Names: Prostatovesiculectomy; Drug: Androgen Receptor Antagonist ARN-509; Given PO; Other Names: ARN-509
Active Comparator: Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP); 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.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Prednisone; Given PO; Other Names: Deltasone; Orasone; .delta.1-Cortisone; 1, 2-Dehydrocortisone; Adasone; Cortancyl; Dacortin; DeCortin; Decortisyl; Decorton; Delta 1-Cortisone; Delta-Dome; Deltacortene; Deltacortisone; Deltadehydrocortisone; Deltison; Deltra; Econosone; Lisacort; Meprosona-F; Metacortandracin; Meticorten; Ofisolona; Panafcort; Panasol-S; Paracort; PRED; Predicor; Predicorten; Prednicen-M; Prednicort; Prednidib; Prednilonga; Predniment; Prednisonum; Prednitone; Promifen; Servisone; SK-Prednisone; Drug: Abiraterone Acetate; Given PO; Other Names: Zytiga; CB7630; Procedure: Radical Prostatectomy; Undergo radical prostatectomy; Other Names: Prostatovesiculectomy; Drug: Androgen Receptor Antagonist ARN-509; Given PO; Other Names: ARN-509; Biological: Gonadotropin-releasing Hormone Analog; Given SC; Other Names: 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
Active Comparator: Arm III (radical prostatectomy); Patients undergo radical prostatectomy.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Radical Prostatectomy; Undergo radical prostatectomy; Other Names: Prostatovesiculectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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
Postoperative continence rate as determined by the Sexual Health Inventory for Men		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
Quality of life as assessed by the AUAss questionnaires		Up to 24 months after surgery
Quality of life as assessed by the EPIC questionnaires		Up to 24 months after surgery

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Saum Ghodoussipour, MD, Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2017
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: October 21, 2016
• First Submitted That Met QC Criteria: October 27, 2016
• First Posted (Estimated): October 31, 2016

Study Record Updates

• Last Update Posted (Estimated): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Prostatic Neoplasms; Adenocarcinoma; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Androstenes; Androstanes; Abiraterone Acetate; Prednisone; Gonadotropin-Releasing Hormone; deltacortene; prednylidene; apalutamide
• Other Study ID Numbers: Pro20160000563; P30CA072720 (U.S. NIH Grant/Contract); NCI-2016-01496 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 081603 (Other Identifier: Rutgers Cancer Institute of New Jersey)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No