A phase II, open-label, single-arm, efficacy, and safety study of MDV3100 in patients with hormone-naïve prostate cancer

177 Background: MDV3100 is a novel androgen receptor (AR) antagonist in clinical development for the treatment of prostate cancer (PCa). Compared to bicalutamide, MDV3100 has higher in vitro AR binding affinity and no evidence of partial agonism. Preliminary phase I-II data show antitumor activity with MDV3100 in men with advanced PCa who were concurrently using androgen deprivation therapy (ADT; Scher HI, et al. Lancet. 2010;375:1437-46). Phase II and III studies in men with progressive and earlier-stage PCa are ongoing. This abstract describes the design of a phase II study of MDV3100 in men with hormone-naïve PCa (HNPCa) who are candidates for ADT. Methods: This 25-week, open-label, single-arm, efficacy and safety study of MDV3100 (160 mg/d orally) will be initiated at ∼20 investigational sites in late 2010 (planned countries: Austria, Belgium, Czech Republic, Denmark, Germany). Inclusion criteria include histologically confirmed, locally advanced PCa (all stages), noncastrate testosterone (T; ≥230 ng/dL), prostate-specific antigen (PSA) ≥2 ng/mL (screening), Eastern Cooperative Oncology Group score of 0, and life expectancy ≥1 year. Exclusion criteria include, among others, previous/current hormonal therapy or chemotherapy for PCa. The primary endpoint is PSA response, defined as an ≥80% decrease from baseline to wk 25. A binary PSA response per patient (wk 25) will be determined, allowing for generation of a PSA response rate (95% CI) from all patients for the study. Secondary endpoints include: PSA dynamics; pharmacokinetics; change in gonadotropin, T, dihydrotestosterone, estradiol, sex-hormone binding globulin, and prolactin levels; and safety/tolerability. Exploratory endpoints include changes in bone mineral density, bone turnover markers, metabolic parameters, and quality of life. Results: The planned enrollment is 60 patients. With a 20% dropout rate, the study will have 80% power to reject the unwanted PSA response rate of ≤50% (5% significance). Efficacy and safety data will be published later. Conclusions: Previous data were in men with castrate levels of T (≤50 ng/dL). This trial will be the first to investigate the use of MDV3100 monotherapy in HNPCa. [Table: see text]