TERRAIN: A randomized, double-blind, phase II study comparing MDV3100 with bicalutamide (Bic) in men with metastatic castrate-resistant prostate cancer (CRPC).

Abstract

TPS4698^ Background: MDV3100 is a novel androgen receptor (AR) signaling inhibitor (ARSI) in clinical development for treatment of prostate cancer (PCa). Compared with Bic in nonclinical CRPC models, MDV3100 showed higher affinity AR binding, inhibited nuclear translocation and AR-DNA binding, showed no evidence of AR agonism, and caused tumor regression in Bic-resistant xenografts. MDV3100 has shown antitumor activity in men with advanced PCa. We present the study design of a trial comparing MDV3100 and Bic in men with progressive metastatic PCa. Methods: Multinational study (Table) with planned enrollment of 370 patients (randomized 1:1 to MDV3100 160 mg/d or Bic 50 mg/d). Inclusion criteria include metastatic (≥2 bone lesions or soft tissue disease at screening) progressive CRPC (≥3 rising prostate-specific antigen [PSA] levels or new bone/soft tissue disease), ongoing stable gonadotropin-releasing hormone (GnRH) analog therapy or surgical castration (serum testosterone <50 ng/dL), Eastern Cooperative Oncology Group performance status 0–1, and life expectancy ≥1 year. Exclusion criteria include previous chemotherapy, current/prior antiandrogens (except if administered for <12 wk and discontinued no less than 6 mo before study). Patients will be stratified by time of bilateral orchiectomy or GnRH analog initiation (before/after diagnosis of metastases) and will receive treatment until occurrence of radiographic progression/skeletal-related event, start of new antineoplastic therapy, or development of an adverse event requiring discontinuation. Results: The primary endpoint is progression-free survival; secondary endpoints are safety, PSA response, and time to PSA progression. Exploratory endpoints include circulating tumor cell conversion rate and quality of life. Patients are currently enrolling. Conclusions: This ongoing, head-to-head, phase II trial is the first to prospectively assess whether MDV3100 can provide improved antitumor effects vs Bic in men with metastatic CRPC. [Table: see text]