The Role of Highly Selective Androgen Receptor (AR) Targeted Therapy in Men With Biochemically Relapsed Hormone Sensitive Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by Aragon Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Aragon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01790126
First received: February 8, 2013
Last updated: April 8, 2016
Last verified: April 2016
  Purpose
The proposed clinical trial will study the effects of 12 months of therapy with ARN-509 alone, or in combination with an LHRH agonist (LHRHa), each compared with LHRHa alone, in men with a rapidly rising serum PSA after prior definitive local therapy for prostate cancer. The endpoints selected reflect measurable short term effects of androgen deprivation therapy (ADT), including quality of life and several metabolic parameters. In addition, the relative effect of each treatment strategy on PSA suppression as well as testosterone recovery (and subsequent PSA progression) after 12 months of therapy will be evaluated.

Condition Intervention Phase
Prostate Cancer
Drug: ARN-509
Drug: LHRH Agonist
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Role of Highly Selective Androgen Receptor (AR) Targeted Therapy in Men With Biochemically Relapsed Hormone Sensitive Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Aragon Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Mean Change From Baseline in Total Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    FACT-P includes a 27-item "core" quality of life measure (FACT-G) grouped into 4 sub-scales: physical, social/family, emotional, and functional well-being. The prostate cancer-specific subscale contains an additional 12 items; 10 of which are prostate cancer specific physical problems. Items are rated on a 5-item Likert scale, from 0, "not at all", to 4, "very much". Total range of scores is from 0 - 156. Higher scores indicate higher degree of functioning and better quality of life.


Secondary Outcome Measures:
  • Time to Prostate-Specific Antigen (PSA) progression [ Time Frame: 7-24 months ] [ Designated as safety issue: No ]
    PSA progression will be defined as a rise to greater than 50% of the baseline serum PSA or rise of 2 ng/mL or more above the nadir, whichever is higher, confirmed by repeat measurement at least 2 weeks later.

  • Percentage of Participants without PSA or radiographic progression and recovery of serum testosterone [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]
    Percentage of participants without evidence of PSA or radiographic progression during the 24-month treatment period and with recovery of serum testosterone at 24 months. Testosterone recovery will be defined as a serum testosterone > 150 ng/dL.

  • Percentage of Participants with a serum PSA < 0.2 nanogram/milliliter (ng/mL) [ Time Frame: Month 7 ] [ Designated as safety issue: No ]
  • Mean change from baseline in body mass index over time [ Time Frame: Baseline up to Month 24 ] [ Designated as safety issue: No ]
    Body Mass Index (BMI) is calculated by dividing the body weight (in kilogram) by the square of height (in meters).

  • Mean change from baseline in Fasting Palsma Glucose over time [ Time Frame: Baseline up to Month 24 ] [ Designated as safety issue: No ]
  • Mean change from Baseline in Fasting Plasma Insulin over time [ Time Frame: Baseline up to Month 24 ] [ Designated as safety issue: No ]
  • Mean change from Baseline in hemoglobin A1C (HbA1C) over time [ Time Frame: Baseline up to Month 24 ] [ Designated as safety issue: No ]
  • Mean change from Baseline in Fasting Lipid Profile over time [ Time Frame: Baseline up to Month 24 ] [ Designated as safety issue: No ]
  • Mean change from Baseline in bone mineral density over time [ Time Frame: Baseline up to Month 24 ] [ Designated as safety issue: No ]
    Bone mineral density will be measured at the femoral neck, and lumbar spine by DEXA.

  • Mean change from Baseline in serum dihydrotestosterone (DHT) levels over time [ Time Frame: Baseline up to Month 24 ] [ Designated as safety issue: No ]
  • Mean change from Baseline in estradiol levels over time [ Time Frame: Baseline up to Month 24 ] [ Designated as safety issue: No ]
  • Number of participants with adverse events [ Time Frame: From signing of informed consent form up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
    An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

  • Number of participants with abnormal findings in physical exams [ Time Frame: From signing of informed consent form up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
  • Number of participants with abnormal findings in laboratory tests [ Time Frame: From signing of informed consent form up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
  • Percentage of Participants emerging with ARF876L mutation at the end of treatment and progression [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]
  • Percentage of Participants expressing RNA markers previously demonstrated to confer resistance ARN509 at Baseline, end of treatment and progression [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: March 2013
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ARN-509
ARN-509 Tablets, 240 mg/day administered orally
Drug: ARN-509
Active Comparator: LHRH agonist + ARN-509
Choice of LHRHa per investigator discretion/site practice guidelines (e.g, Eligard®, Zoladex®, Lupron Depot®, Trelstar®) and ARN-509 Tablets, 240 mg/day administered orally
Drug: ARN-509 Drug: LHRH Agonist
Other Names:
  • Eligard®
  • Lupron Depot®
  • Zoladex®
  • Trelstar®
Active Comparator: LHRH agonist
Choice of LHRHa per investigator discretion/site practice guidelines (e.g., Eligard®, Zoladex®, Lupron Depot®, Trelstar®).
Drug: LHRH Agonist
Other Names:
  • Eligard®
  • Lupron Depot®
  • Zoladex®
  • Trelstar®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Histologically proven adenocarcinoma of the prostate
  • Rising PSA after prior definitive local therapy (radical prostatectomy, external beam radiation, or brachytherapy) or combination of radical prostatectomy and radiotherapy with curative intent
  • PSA doubling time less than or equal to 12 months
  • No evidence of metastatic disease on imaging by whole body bone scan and computerized tomography (CT) or Magnetic Resonance Imaging (MRI) of the abdomen/pelvis within 6 weeks prior to randomization
  • Minimum PSA 1.0 ng/mL if prior radical prostatectomy +/- adjuvant or salvage radiation; nadir + 2.0 ng/mL if prior RT without prior radical prostatectomy
  • Prior androgen deprivation therapy (ADT) allowed if last dose was greater than (>) 6 months prior to randomization
  • No prior androgen deprivation therapy (ADT) or anti-androgen for biochemical relapse
  • Serum testosterone > 150 ng/dL at study entry
  • No history of seizures or medical conditions which may lower seizure threshold

Key Exclusion Criteria:

  • Use of 5-alpha reductase antagonist (i.e. finasteride, dutasteride) within 6 weeks prior to randomization
  • Use of antiandrogen (e.g. flutamide, nilutamide, bicalutamide) within 6 weeks prior to randomization
  • Prior bilateral orchiectomy
  • Prior treatment with ADT for biochemically relapsed prostate cancer. Prior ADT as neo-adjuvant, concurrent, and/or adjuvant treatment following salvage radiation therapy or prostatectomy for biochemically relapsed disease is allowed provided last dose of ADT is greater than (>) 6 months prior to randomization and the Screening serum testosterone level is greater than or equal to (≥)150 ng/dL
  • Use of systemic steroids at an equivalent dose of prednisone 5 mg/day or higher at randomization
  • Any history of seizures or medical condition which lowers seizure threshold
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01790126

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

Locations
United States, Arizona
Recruiting
Scottsdale, Arizona, United States
United States, California
Recruiting
San Francisco, California, United States
United States, Illinois
Recruiting
Chicago, Illinois, United States
United States, Oregon
Recruiting
Portland, Oregon, United States
United States, Washington
Recruiting
Seattle, Washington, United States
Sponsors and Collaborators
Aragon Pharmaceuticals, Inc.
Investigators
Study Director: Aragon Pharmaceuticals, Inc Clinical Trial Aragon Pharmaceuticals, Inc.
  More Information

Additional Information:
Responsible Party: Aragon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01790126     History of Changes
Other Study ID Numbers: CR103305  ARN-509-002 
Study First Received: February 8, 2013
Last Updated: April 8, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Aragon Pharmaceuticals, Inc.:
Men with Biochemically Relapsed Hormone Sensitive Prostate Cancer

Additional relevant MeSH terms:
Genital Diseases, Male
Prostatic Diseases
Prostatic Neoplasms
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Leuprolide
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Fertility Agents
Fertility Agents, Female
Physiological Effects of Drugs
Reproductive Control Agents

ClinicalTrials.gov processed this record on May 26, 2016