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.

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