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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

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ClinicalTrials.gov Identifier: NCT02949284
Recruitment Status : Recruiting
First Posted : October 31, 2016
Last Update Posted : February 26, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Isaac Yi Kim, MD, PhD, MBA, Rutgers, The State University of New Jersey

Brief 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.

Condition or disease Intervention/treatment Phase
Stage II Prostate Adenocarcinoma Stage III Prostate Adenocarcinoma Drug: Abiraterone Acetate Drug: Androgen Receptor Antagonist ARN-509 Biological: Gonadotropin-releasing Hormone Analog Drug: Prednisone Other: Quality-of-Life Assessment Other: Questionnaire Administration Procedure: Radical Prostatectomy Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 20, 2017
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021


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.
Drug: Androgen Receptor Antagonist ARN-509
Given PO
Other Name: ARN-509

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Procedure: Radical Prostatectomy
Undergo radical prostatectomy
Other Name: Prostatovesiculectomy

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.
Drug: Abiraterone Acetate
Given PO
Other Names:
  • CB7630
  • Zytiga

Drug: Androgen Receptor Antagonist ARN-509
Given PO
Other Name: 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

Drug: Prednisone
Given PO
Other Names:
  • .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-Prednisone

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Procedure: Radical Prostatectomy
Undergo radical prostatectomy
Other Name: Prostatovesiculectomy

Active Comparator: Arm III (radical prostatectomy)
Patients undergo radical prostatectomy.
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Procedure: Radical Prostatectomy
Undergo radical prostatectomy
Other Name: Prostatovesiculectomy




Primary Outcome Measures :
  1. Post-surgical potency rate defined as proportion of patients with International Index of Erectile Function score >= 17 [ Time Frame: At 12 months ]
    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 :
  1. Change in tumor volume on pelvic MRI after neoadjuvant therapy [ Time Frame: Baseline to week 13 ]
    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.

  2. Number of patients with biochemical recurrence defined using the Prostate Cancer Clinical Trials Working Group 2 definition [ Time Frame: Up to 5 years ]
  3. Number of patients with pathological T0 [ Time Frame: Up to 5 years ]
  4. Number of patients with positive surgical margins [ Time Frame: Up to 5 years ]
  5. Postoperative continence rate as determined by the American Urological Association Symptom Score (AUAss) [ Time Frame: Up to 24 months after surgery ]
  6. Postoperative continence rate as determined by the Sexual Health Inventory for Men [ Time Frame: Up to 24 months after surgery ]
  7. Postoperative continence rate as determined by the Expanded Prostate Cancer Index Composite (EPIC) [ Time Frame: Up to 24 months after surgery ]
  8. Quality of life as assessed by the AUAss questionnaires [ Time Frame: Up to 24 months after surgery ]
  9. Quality of life as assessed by the EPIC questionnaires [ Time Frame: Up to 24 months after surgery ]


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02949284


Locations
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United States, California
City of Hope Comprehensive Cancer Center Not yet recruiting
Duarte, California, United States, 91010
Contact: Bertram Yuh    626-394-2383    byuh@coh.org   
Principal Investigator: Bertram Yuh         
United States, New Jersey
Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Isaac Y. Kim    732-235-2043    kimiy@cinj.rutgers.edu   
Principal Investigator: Isaac Y. Kim         
Sponsors and Collaborators
Rutgers, The State University of New Jersey
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Isaac Kim Rutgers Cancer Institute of New Jersey

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Responsible Party: Isaac Yi Kim, MD, PhD, MBA, Professor of Surgery, RWJMS, Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier: NCT02949284     History of Changes
Other Study ID Numbers: 081603
NCI-2016-01496 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Pro20160000563
081603 ( Other Identifier: Rutgers Cancer Institute of New Jersey )
P30CA072720 ( U.S. NIH Grant/Contract )
First Posted: October 31, 2016    Key Record Dates
Last Update Posted: February 26, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Hormones
Prednisone
Estrogens, Conjugated (USP)
Methyltestosterone
Prolactin Release-Inhibiting Factors
Cortisone
Abiraterone Acetate
Androgens
Ascorbic Acid
Deslorelin
Androgen Receptor Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Inflammatory Agents
Glucocorticoids
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action