Background: Ra-223, a first-in-class alpha-emitting radiopharmaceutical targeting bone metastases, reduced risk of death by 30% and delayed time to first symptomatic skeletal event (SSE) versus placebo (15.6 vs 9.8 mo; HR = 0.66) in phase 3 ALSYMPCA (Parker et al. NEJM 2013, Sartor et al. Lancet Oncol 2014). Ra-223 favorable safety profile and lack of significant toxicity support combining it with other agents. Abiraterone improved radiologic progression-free survival (rPFS) and overall survival (OS) (Ryan et al. NEJM 2012) in chemotherapy-naïve men with mCRPC; it has no overlapping toxicity with Ra-223. This study investigates efficacy and safety of Ra-223 + abiraterone versus abiraterone alone in chemotherapy-naïve pts with mCRPC to bone. Methods: This phase 3, double-blind, placebo-controlled, multinational trial (ERA 223, NCT02043678) will randomize ~ 800 pts with asymptomatic or mildly symptomatic chemotherapy-naïve, bone-predominant mCRPC 1:1 to receive abiraterone (oral 1000 mg daily) and prednisone (oral 5 mg twice daily) + Ra-223 (50 kBq/kg IV) q 4 wk for 6 cycles or matching placebo until an SSE or death. Stratification is by geographic region, concurrent use of denosumab or bisphosphonates, and total alkaline phosphatase. The primary end point is SSE-free survival. Secondary end points include OS; time to opiate use for cancer pain, pain progression, and cytotoxic chemotherapy; rPFS; and acute and long-term safety. Pts are assessed at each treatment visit for efficacy, safety, and health-related quality of life, and every 3 months for progression and long-term safety. Pts who complete all study treatment and have no SSE enter active follow-up. Long-term follow-up begins after pts experience an SSE and ends 7 years after the last Ra-223 dose or at death, loss to follow-up, or withdrawal. SSE-free survival will be analyzed using a stratified log-rank test, accounting for stratification. Kaplan-Meier estimates will be produced for both treatment groups. As of January 15, 2015, 118 pts were screened.Clinical trial information: NCT02043678