Spartan - a Randomized Double-Blind, Comparative Study of Arn-509 Plus Androgen Deprivation Therapy (Adt) Vs Adt Alone in Non-Metastatic Castration-Resistant Prostate Cancer (M0-Crpc)

Abstract

Background: ADT is the standard of care for patients (pts) with metastatic prostate cancer and is frequently used for pts with non-metastatic prostate cancer. Initial ADT achieves responses in nearly all pts, but most progress to castration-resistant disease within a few years. Among men with M0-CRPC, a rising prostate-specific antigen (PSA) heralds the development of metastases and associated morbidity and mortality. Prevention of metastases is a major unmet medical need for pts with M0-CRPC. ARN-509 (ARN) is a potent and selective androgen receptor (AR) antagonist that inhibits AR nuclear translocation and DNA binding without significant AR agonist properties (Clegg N et al. Cancer Res. 2012). ARN demonstrates a 12- and 24-week PSA response rate of 91% in M0-CRPC pts and an excellent safety profile (Smith MR et al. ASCO GU 2013; Smith MR et al. ESMO 2013). Trial design: This is a multicenter, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy and safety of ARN in pts with M0-CRPC at high risk for progression (PSA doubling time [PSADT] ≤ 10 months). Continuous ADT is mandatory in order to maintain castrate concentrations of testosterone (< 50 ng/dL). Pts are stratified based on PSADT (≤ 6 vs > 6 months), baseline use of bone-sparing agents for osteoporosis, and presence of locoregional disease, and randomized (2:1) to ARN + ADT or placebo + ADT. The absence of distant metastasis at screening is documented by central radiographic review. The primary end point is metastasis-free survival. Secondary end points include overall survival and other clinically relevant end points. Approximately 1200 pts will be randomized to provide appropriate statistical rigor to detect the hypothesized risk reduction in metastasis or death. This study uses group sequential design, including an interim analysis. The stratified log rank test will be used for the analysis. An independent data monitoring committee is commissioned to conduct reviews of the safety and efficacy data. Approximately 300 sites from 24 countries will participate. Pts are being screened and enrolled as of September 2013. (ClinicalTrials.gov Identifier: NCT01946204). This abstract was accepted and previously presented at the 2014 ASCO Annual Meeting (TPS5100). Disclosure: B. Tombal: has received speaker and investigator fees from Johnson & Johnson; S.M. Shreeve, G.C. Trudel, A. Sosa, T. Kheoh: and M. Yu: is an employee of Janssen and holds stock in Johnson & Johnson; M.R. Smith: has served as a consultant/advisor to and received research funding from Janssen; S. Oudard: has served as a consultant/advisor to and received honoraria from Pfizer, Bayer, Novartis, Janssen, Takeda, and Sanofi. All other authors have declared no conflicts of interest.