Phase 2 Trial of GTx-758, an Estrogen Receptor Alpha Agonist, in Men With Castration-Resistant Prostate Cancer

Abstract

Introduction: Novel estrogen therapy has the potential to be efficacious, with a favorable adverse event profile, in castration-resistant prostate cancer (CRPC). We performed a phase 2 trial to assess the ability of GTx-758, an oral selective estrogen receptor alpha agonist, to result in a ≥ 50% PSA decline by day 90, modulate free testosterone and sex hormone–binding globulin (SHBG) levels, and affect estrogen deficiency adverse events. Patients and Methods: CRPC patients received GTx-758 in two dose cohorts, 125 and 250 mg/d. The primary endpoint was the proportion of subjects who experienced a ≥ 50% PSA decline by day 90. Secondary endpoints included changes in testosterone, SHBG, bone turnover markers, and hot flashes, as well as safety. Results: Four (10.5%) of 38 (95% CI, 2.9, 24.8; P = .120) and 10 (25.6%) of 39 patients (95% CI, 13.0, 42.1; P