ARAMIS trial: Efficacy and safety of ODM-201 in men with high-risk nonmetastatic castration-resistant prostate cancer

Abstract

Background: Treatment for nonmetastatic castration-resistant prostate cancer (nmCRPC) other than continuing androgen deprivation therapy (ADT) remains an unmet need. There are no approved therapies for preventing metastatic disease in nmCRPC. Pts with nmCRPC who have shorter prostate-specific antigen doubling time (PSADT) are at higher risk for metastatic disease or death. ODM-201, a novel second-generation oral androgen receptor inhibitor, has demonstrated a tolerable safety profile and antineoplastic activity in progressive CRPC. The ARAMIS trial will evaluate the efficacy and safety of ODM-201 in high-risk nmCRPC pts. Methods: This randomized, double-blind, placebo-controlled phase 3 trial (NCT02200614 ) involves > 450 sites in > 33 countries. 1500 pts on ADT will be randomized 2:1 to ODM-201 600 mg or placebo BID. Pts will be stratified by PSADT and baseline bone-targeting agent use. Eligibility criteria include nmCRPC, PSADT = 2 ng/mL. 90% power to detect a target hazard ratio of 0.75 is based on a 2-sided log-rank test at an overall significance level of 0.05. The primary endpoint is metastasis-free survival based on central independent review of bone scan and CT/MRI every 16 weeks. Secondary endpoints are overall survival, time to first symptomatic skeletal event, initiation of first cytotoxic chemotherapy for PC, pain progression, and first opioid use. Additional endpoints are progression-free survival, time to first PC-related invasive procedure, initiation of subsequent antineoplastic therapy, PSA progression, change in ECOG status, and changes in health-related quality of life. Time to event endpoints will be analyzed using a stratified log-rank test, and Kaplan-Meier estimates will be produced for both treatment groups. The ARAMIS trial is open and recruiting, the first pt was randomized in October 2014.