Clinical Trials /

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

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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 IDs

  • ORG STUDY ID: 081603
  • SECONDARY ID: NCI-2016-01496
  • SECONDARY ID: Pro20160000563
  • SECONDARY ID: 081603
  • SECONDARY ID: P30CA072720
  • NCT ID: NCT02949284

Conditions

  • Stage II Prostate Adenocarcinoma
  • Stage III Prostate Adenocarcinoma

Interventions

DrugSynonymsArms
Abiraterone AcetateCB7630, ZytigaArm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)
Androgen Receptor Antagonist ARN-509ARN-509Arm I (androgen receptor ARN-509, radical prostatectomy)
Gonadotropin-releasing Hormone AnalogGnRH 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 AnalogArm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)
Prednisone.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-PrednisoneArm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (androgen receptor ARN-509, radical prostatectomy)ExperimentalPatients receive androgen receptor antagonist ARN-509 PO daily for 3 months. Patients then undergo radical prostatectomy.
  • Androgen Receptor Antagonist ARN-509
Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)Active ComparatorPatients 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.
  • Abiraterone Acetate
  • Androgen Receptor Antagonist ARN-509
  • Prednisone
Arm III (radical prostatectomy)Active ComparatorPatients undergo radical prostatectomy.

    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)
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:N/A
    Eligible Gender:Male
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Post-surgical potency rate defined as proportion of patients with International Index of Erectile Function score >= 17
    Time Frame:At 12 months
    Safety Issue:
    Description: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.

    Secondary Outcome Measures

    Measure:Change in tumor volume on pelvic MRI after neoadjuvant therapy
    Time Frame:Baseline to week 13
    Safety Issue:
    Description: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.
    Measure:Number of patients with biochemical recurrence defined using the Prostate Cancer Clinical Trials Working Group 2 definition
    Time Frame:Up to 5 years
    Safety Issue:
    Description:
    Measure:Number of patients with pathological T0
    Time Frame:Up to 5 years
    Safety Issue:
    Description:
    Measure:Number of patients with positive surgical margins
    Time Frame:Up to 5 years
    Safety Issue:
    Description:
    Measure:Postoperative continence rate as determined by the American Urological Association Symptom Score (AUAss)
    Time Frame:Up to 24 months after surgery
    Safety Issue:
    Description:
    Measure:Postoperative continence rate as determined by the Sexual Health Inventory for Men
    Time Frame:Up to 24 months after surgery
    Safety Issue:
    Description:
    Measure:Postoperative continence rate as determined by the Expanded Prostate Cancer Index Composite (EPIC)
    Time Frame:Up to 24 months after surgery
    Safety Issue:
    Description:
    Measure:Quality of life as assessed by the AUAss questionnaires
    Time Frame:Up to 24 months after surgery
    Safety Issue:
    Description:
    Measure:Quality of life as assessed by the EPIC questionnaires
    Time Frame:Up to 24 months after surgery
    Safety Issue:
    Description:

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Rutgers, The State University of New Jersey

    Last Updated

    February 3, 2017