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 January 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: February 5, 2016
Last verified: January 2016

February 8, 2013
February 5, 2016
March 2013
January 2019   (final data collection date for primary outcome measure)
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.
Mean change in quality of life (QOL) measured by total FACT-P score [ Time Frame: 12 months ] [ Designated as safety issue: No ]
To compare the mean change in QOL as measured by total FACT-P score after 12 months of therapy with ARN-509 monotherapy and ARN-509 + LHRHa versus LHRHa monotherapy, in men with biochemically relapsed prostate cancer.
Complete list of historical versions of study NCT01790126 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Quality of Life Instruments [ Time Frame: 12-24 months ] [ Designated as safety issue: No ]
    To compare ARN-509 monotherapy and ARN-509 + LHRHa vs. LHRHa monotherapy with regards to the mean change in QOL at 24 months as measured by FACT-P, EORTC QLQ-C30/PR-25 and the SHIM scale.
  • PSA Modulation [ Time Frame: Approx. 7-24 months ] [ Designated as safety issue: No ]
    To compare ARN-509 monotherapy and ARN-509 + LHRHa vs. LHRHa monotherapy with regards to the proportion of patients who demonstrate testosterone recovery without evidence of PSA or radiographic progression at 24 months, the proportion of patients with a nadir PSA <0.2 ng/mL after 7 months, and the time to PSA progression.
  • Metabolic and Hormonal Changes [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To compare ARN-509 monotherapy and ARN-509 + LHRHa vs. LHRHa monotherapy with regards to the mean change in baseline in markers of insulin resistance, fasting lipid profile, bone mineral density, serum DHT, and estradiol levels after 12 months, and the time to serum testosterone recovery to >50 ng/dL and >150 ng/dL after cessation of protocol therapy for 12 months.
  • Toxicity [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To characterize the safety profile of ARN-509 alone and in combinations with a LHRHa based on CTCAE v4.0.
Not Provided
Not Provided
 
The Role of Highly Selective Androgen Receptor (AR) Targeted Therapy in Men With Biochemically Relapsed Hormone Sensitive Prostate Cancer
The Role of Highly Selective Androgen Receptor (AR) Targeted Therapy in Men With Biochemically Relapsed Hormone Sensitive Prostate Cancer
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.
Not Provided
Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • Drug: ARN-509
  • Drug: LHRH Agonist
    Other Names:
    • Eligard®
    • Lupron Depot®
    • Zoladex®
    • Trelstar®
  • Active Comparator: ARN-509
    ARN-509 Tablets, 240 mg/day administered orally
    Intervention: 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
    Interventions:
    • Drug: ARN-509
    • Drug: LHRH Agonist
  • Active Comparator: LHRH agonist
    Choice of LHRHa per investigator discretion/site practice guidelines (e.g., Eligard®, Zoladex®, Lupron Depot®, Trelstar®).
    Intervention: Drug: LHRH Agonist
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
90
January 2020
January 2019   (final data collection date for primary outcome measure)

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
Male
18 Years and older
No
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
United States
 
NCT01790126
CR103305, ARN-509-002
No
Not Provided
Not Provided
Aragon Pharmaceuticals, Inc.
Aragon Pharmaceuticals, Inc.
Not Provided
Study Director: Aragon Pharmaceuticals, Inc Clinical Trial Aragon Pharmaceuticals, Inc.
Aragon Pharmaceuticals, Inc.
January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP