Clinical trial NCT01790126: The Role of Highly Selective Androgen Receptor (AR) Targeted Therapy in Men With Biochemically Relapsed Hormone Sensitive Prostate Cancer
Official title: The Role of Highly Selective Androgen Receptor (AR) Targeted Therapy in Men With Biochemically Relapsed Hormone Sensitive Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Men with Biochemically Relapsed Hormone Sensitive Prostate Cancer
Lead sponsor: Aragon Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2013-02-13
Enrollment: 90
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Total Score at 12 Months
timeFrame: Baseline, at 12 months
Secondary outcomes:
measure: Change From Baseline in FACT-P Total Score at 3 and 24 Months
timeFrame: Baseline, at 3 and 24 months
measure: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score at 3, 12 and 24 Months
timeFrame: Baseline, at 3, 12 and 24 months
measure: Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months
timeFrame: Baseline, at 3, 12 and 24 months
measure: Change From Baseline in Sexual Health Inventory for Men (SHIM) Total Score at 3, 12, 24 Months
timeFrame: Baseline, at 3, 12, 24 months
measure: Time to Prostate Specific Antigen (PSA) Progression Based on Modified Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria
timeFrame: Up to 24 months
measure: Percentage of Participants Without PSA or Radiographic Progression and With Recovery of Serum Testosterone
timeFrame: Up to 24 months
measure: Percentage of Participants With a Serum PSA Less Than 0.2 ng/mL
timeFrame: From 7 to 24 months
measure: Change From Baseline in Body Mass Index (BMI)
timeFrame: Baseline, Day 1 (Cycle 1), Day 28 (Cycle 1, 2, 4, 5, 7, 8, 10 and 11), Day 35 (Cycle 3, 6, 9 and 12) and endpoint (up to 24 months)
measure: Change From Baseline in Fasting Plasma Glucose
timeFrame: Baseline, Day 35 (Cycle 3, 6, 9 and 12)
measure: Change From Baseline in Glycated Hemoglobin (HbA1C)
timeFrame: Baseline, Day 35 (Cycle 3, 6, 9 and 12)
measure: Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides
timeFrame: Baseline, Day 35 (Cycle 3, 6, 9 and 12)
measure: Change From Baseline in Bone Mineral Density (BMD)
timeFrame: Baseline, Cycle 12 Day 35
measure: Median Time to Serum Testosterone Recovery to Greater Than (>) 50 ng/dL (Non-castrate) and > 150 ng/dL
timeFrame: Month 13 to Month 24
measure: Change From Baseline in Serum Dihydrotestosterone (DHT) Levels
timeFrame: Baseline, Day 35 (Cycle 6 and Cycle 12)
measure: Change From Baseline in Estradiol Levels
timeFrame: Baseline, Day 35 (Cycle 6 and Cycle 12)
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From date of 1st dose of study drug to date of last dose of study drug plus 30 days (up to 6 years)
Other outcomes:
Locations:
city: Scottsdale
country: United States
state: Arizona
city: San Francisco
country: United States
state: California
city: Chicago
country: United States
state: Illinois
city: Portland
country: United States
state: Oregon
city: Seattle
country: United States
state: Washington
Study officials:
affiliation: Aragon Pharmaceuticals, Inc.
name: Aragon Pharmaceuticals, Inc Clinical Trial
role: STUDY_DIRECTOR
References: