Background: There is no standard treatment for nmCRPC besides continuing androgen deprivation therapy (ADT). Preventing metastatic disease in nmCRPC is a major unmet need. Patients with nmCRPC who have shorter PSA doubling time (PSADT) are at high risk for metastatic disease or death (Smith et al. J Clin Oncol. 2013;31:3800-6). ODM-201, a novel second-generation oral androgen receptor inhibitor, has shown an excellent safety profile and promising anticancer activity in progressive CRPC (Fizazi et al. Lancet Oncol. 2014;15:975-85). The ARAMIS trial aims to evaluate the efficacy and safety of ODM-201 in high-risk nmCRPC. Methods: This international, randomized, double-blind, placebo-controlled phase 3 trial (NCT02200614) involves over 300 sites in more than 30 countries. 1500 patients on ADT will be randomized 2:1 to ODM-201 600 mg or placebo twice daily. Patients will be stratified by PSADT and baseline use of bone-targeting agent. Eligibility criteria include nmCRPC, PSADT ≤ 10 months, and screening PSA ≥ 2 ng/mL. The primary endpoint is metastasis-free survival based on central independent review of bone scan and CT/MRI every 16 weeks; progression of regional disease is not considered metastasis. Secondary endpoints are OS, time to first symptomatic skeletal event (SSE), initiation of first cytotoxic chemotherapy for prostate cancer, pain progression, and first opioid use. Additional endpoints are PFS, time to first prostate cancer–related invasive procedure, initiation of subsequent antineoplastic therapy, PSA progression, change in ECOG status, and changes in health-related QoL. Endpoints will be analyzed using a stratified log-rank test, accounting for stratification. The trial has 90% power to detect a target hazard ratio of 0.75 based on a 2-sided log-rank test at an overall significance level of 0.05. Kaplan-Meier estimates will be produced for both treatment groups. The ARAMIS trial is open and recruiting, with the first patient randomized in October 2014. Clinical trial information: NCT02200614