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

Stage II Prostate Adenocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02949284
• Other study ID #: Pro20160000563
• Secondary ID: NCI-2016-01496Pr
• Status: Recruiting
• Phase: Phase 2
• Start date: June 20, 2017
• Est. completion date: January 20, 2024

Study information

• Verified date: September 2023
• Source: Rutgers, The State University of New Jersey
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: January 20, 2024
• Est. primary completion date: January 20, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Adenocarcinoma
• Prostatic Neoplasms
• Stage II Prostate Adenocarcinoma
• Stage III Prostate Adenocarcinoma

Intervention

Drug:
• Abiraterone Acetate
Given PO
• Androgen Receptor Antagonist ARN-509
Given PO

Biological:
• Gonadotropin-releasing Hormone Analog
Given SC

Drug:
• Prednisone
Given PO

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Procedure:
• Radical Prostatectomy
Undergo radical prostatectomy

Locations

Country	Name	City	State
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale Cancer Center	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Rutgers, The State University of New Jersey	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Number of patients with biochemical recurrence defined using the Prostate Cancer Clinical Trials Working Group 2 definition		Up to 5 years
Secondary	Number of patients with pathological T0		Up to 5 years
Secondary	Number of patients with positive surgical margins		Up to 5 years
Secondary	Postoperative continence rate as determined by the American Urological Association Symptom Score (AUAss)		Up to 24 months after surgery
Secondary	Postoperative continence rate as determined by the Sexual Health Inventory for Men		Up to 24 months after surgery
Secondary	Postoperative continence rate as determined by the Expanded Prostate Cancer Index Composite (EPIC)		Up to 24 months after surgery
Secondary	Quality of life as assessed by the AUAss questionnaires		Up to 24 months after surgery
Secondary	Quality of life as assessed by the EPIC questionnaires		Up to 24 months after surgery