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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary:
Sponsor: Aragon Pharmaceuticals, Inc.

Current Primary Outcome: Mean Change From Baseline in Total Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score [ Time Frame: 12 months ]

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.


Original Primary Outcome: Mean change in quality of life (QOL) measured by total FACT-P score [ Time Frame: 12 months ]

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.


Current Secondary Outcome:

  • Time to Prostate-Specific Antigen (PSA) progression [ Time Frame: 7-24 months ]
    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 ]
    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 ]
  • Mean change from baseline in body mass index over time [ Time Frame: Baseline up to Month 24 ]
    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 ]
  • Mean change from Baseline in Fasting Plasma Insulin over time [ Time Frame: Baseline up to Month 24 ]
  • Mean change from Baseline in hemoglobin A1C (HbA1C) over time [ Time Frame: Baseline up to Month 24 ]
  • Mean change from Baseline in Fasting Lipid Profile over time [ Time Frame: Baseline up to Month 24 ]
  • Mean change from Baseline in bone mineral density over time [ Time Frame: Baseline up to Month 24 ]
    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 ]
  • Mean change from Baseline in estradiol levels over time [ Time Frame: Baseline up to Month 24 ]
  • 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 ]
    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 ]
  • 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 ]
  • Percentage of Participants emerging with ARF876L mutation at the end of treatment and progression [ Time Frame: up to 24 months ]
  • 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 ]


Original Secondary Outcome:

  • Quality of Life Instruments [ Time Frame: 12-24 months ]
    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 ]
    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 ]
    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 ]
    To characterize the safety profile of ARN-509 alone and in combinations with a LHRHa based on CTCAE v4.0.


Information By: Aragon Pharmaceuticals, Inc.

Dates:
Date Received: February 8, 2013
Date Started: March 2013
Date Completion: January 2020
Last Updated: March 17, 2017
Last Verified: March 2017