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

Rutgers The State University of New Jersey

Status and phase: Active, not recruiting; Phase 2

Conditions: Stage III Prostate Adenocarcinoma; Stage II Prostate Adenocarcinoma

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02949284

P30CA072720 (U.S. NIH Grant/Contract)

NCI-2016-01496 (Registry Identifier)

081603 (Other Identifier)

Pro20160000563

Details and patient eligibility

About

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.

Full 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.

Enrollment: 90 estimated patients

Sex: Male

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 3 patient groups

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

Experimental group

Description:

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

Treatment:

Other: Questionnaire Administration

Procedure: Radical Prostatectomy

Other: Quality-of-Life Assessment

Drug: Androgen Receptor Antagonist ARN-509

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

Active Comparator group

Description:

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.

Treatment:

Drug: Prednisone

Biological: Gonadotropin-releasing Hormone Analog

Other: Questionnaire Administration

Drug: Abiraterone Acetate

Procedure: Radical Prostatectomy

Other: Quality-of-Life Assessment

Drug: Androgen Receptor Antagonist ARN-509

Arm III (radical prostatectomy)

Active Comparator group

Description:

Patients undergo radical prostatectomy.

Treatment:

Other: Questionnaire Administration

Procedure: Radical Prostatectomy

Other: Quality-of-Life Assessment