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

Clinicaltrials.gov ID: NCT02949284
db-list-check Status RECRUITING
b-loader Phase PHASE2
b-people Age All Ages
b-bullseye-arrow Enrollments 90

Conditions

Stage II Prostate Adenocarcinoma, Stage III Prostate Adenocarcinoma

Drugs

Abiraterone Acetate, Androgen Receptor Antagonist ARN-509, Prednisone

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.

Locations

2 locations Found with status Recruiting

Status

  • RECRUITING

Contact Person

Principal Investigator

  • Saum Ghodoussipour, MD

Status

  • RECRUITING

Contact Person

Principal Investigator

  • Saum Ghodoussipour, MD

Eligibility Criteria

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

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

    Description:

    Given PO
  • OTHER:

    Quality-of-Life Assessment

    Description:

    Ancillary studies
  • OTHER:

    Questionnaire Administration

    Description:

    Ancillary studies
  • PROCEDURE:

    Radical Prostatectomy

    Description:

    Undergo 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

    Description:

    Given PO
  • DRUG:

    Androgen Receptor Antagonist ARN-509

    Description:

    Given PO
  • BIOLOGICAL:

    Gonadotropin-releasing Hormone Analog

    Description:

    Given SC
  • DRUG:

    Prednisone

    Description:

    Given PO
  • OTHER:

    Quality-of-Life Assessment

    Description:

    Ancillary studies
  • OTHER:

    Questionnaire Administration

    Description:

    Ancillary studies
  • PROCEDURE:

    Radical Prostatectomy

    Description:

    Undergo radical prostatectomy

Arm III (radical prostatectomy)

ACTIVE_COMPARATOR

Patients undergo radical prostatectomy.

  • OTHER:

    Quality-of-Life Assessment

    Description:

    Ancillary studies
  • OTHER:

    Questionnaire Administration

    Description:

    Ancillary studies
  • PROCEDURE:

    Radical Prostatectomy

    Description:

    Undergo radical prostatectomy

Outcome Measures

Primary Outcome Measures

Post-surgical potency rate defined as proportion of patients with International Index of Erectile Function score >= 17

Time Frame: At 12 months

Secondary Outcome Measures

Change in tumor volume on pelvic MRI after neoadjuvant therapy

Time Frame: Baseline to week 13

Number of patients with biochemical recurrence defined using the Prostate Cancer Clinical Trials Working Group 2 definition

Time Frame: Up to 5 years

Number of patients with pathological T0

Time Frame: Up to 5 years

Number of patients with positive surgical margins

Time Frame: Up to 5 years

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

Time Frame: Up to 24 months after surgery

Postoperative continence rate as determined by the Sexual Health Inventory for Men

Time Frame: Up to 24 months after surgery

Postoperative continence rate as determined by the Expanded Prostate Cancer Index Composite (EPIC)

Time Frame: Up to 24 months after surgery

Quality of life as assessed by the AUAss questionnaires

Time Frame: Up to 24 months after surgery

Quality of life as assessed by the EPIC questionnaires

Time Frame: Up to 24 months after surgery

Timeline

  • Last Updated
    September 26, 2023
  • Start Date
    October 31, 2016
  • Today
    February 5, 2025
  • Completion Date ( Estimated )
    January 20, 2024

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