F13 - Era 223-A Phase 3 Trial of Radium-223 Dichloride (Ra-223) in Combination with Abiraterone Acetate (Aa) and prednisone in the treatment of asymptomatic or mildly symptomatic chemotherapynaïve patients with bone-predominant metastatic Castration Resistant Prostate Cancer (Crpc)

Abstract

Background: Ra-223, a first-in-class alpha-radiopharmaceutical targeting bone metastases (mets), 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 the phase 3 ALSYMPCA trial (Parker et al. NEJM 2013). Ra-223 has favorable safety, and the lack of significant toxicity supports combining Ra-223 with other agents. AA improved radiologic progression-free survival (rPFS) and overall survival (OS) (Ryan et al. NEJM 2012), and its safety profile indicates no overlapping toxicity with Ra-223. This study investigates the efficacy and safety of Ra-223 plus AA versus AA alone in chemotherapy-naïve patients (pts) with bone-metastatic CRPC.Trial design: This phase 3, double-blind, placebo-controlled, multinational trial (ERA 223, NCT02043678) will randomize approximately 800 pts with asymptomatic or mildly symptomatic, chemotherapy-naïve, bone-predominant metastatic CRPC 1:1 to receive Ra-223 (50 kBq/kg IV) every 4 weeks for 6 cycles or matching placebo plus AA (oral 1000 mg daily) and prednisone (oral 5 mg twice daily), followed by AA plus prednisone thereafter until an SSE or death occurs. Randomization is stratified 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, time to pain progression, time to cytotoxic chemotherapy, rPFS, and acute and long-term safety. All 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 do not have an SSE enter an active follow-up period. Long-term follow-up begins after pts experience an SSE and ends 7 years after the last dose of Ra-223 or at death, loss to follow-up, or withdrawal. This trial is currently recruiting pts. Background: Ra-223, a first-in-class alpha-radiopharmaceutical targeting bone metastases (mets), 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 the phase 3 ALSYMPCA trial (Parker et al. NEJM 2013). Ra-223 has favorable safety, and the lack of significant toxicity supports combining Ra-223 with other agents. AA improved radiologic progression-free survival (rPFS) and overall survival (OS) (Ryan et al. NEJM 2012), and its safety profile indicates no overlapping toxicity with Ra-223. This study investigates the efficacy and safety of Ra-223 plus AA versus AA alone in chemotherapy-naïve patients (pts) with bone-metastatic CRPC. Trial design: This phase 3, double-blind, placebo-controlled, multinational trial (ERA 223, NCT02043678) will randomize approximately 800 pts with asymptomatic or mildly symptomatic, chemotherapy-naïve, bone-predominant metastatic CRPC 1:1 to receive Ra-223 (50 kBq/kg IV) every 4 weeks for 6 cycles or matching placebo plus AA (oral 1000 mg daily) and prednisone (oral 5 mg twice daily), followed by AA plus prednisone thereafter until an SSE or death occurs. Randomization is stratified 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, time to pain progression, time to cytotoxic chemotherapy, rPFS, and acute and long-term safety. All 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 do not have an SSE enter an active follow-up period. Long-term follow-up begins after pts experience an SSE and ends 7 years after the last dose of Ra-223 or at death, loss to follow-up, or withdrawal. This trial is currently recruiting pts.