A Phase II, Nonrandomized Open Trial Assessing Pain Efficacy with Radium-223 in Symptomatic Metastatic Castration-resistant Prostate Cancer

Background Prostate Cancer Working Group 3 and FDA guidelines recommend a standardized approach to pain assessment in preapproval trials. No prior trial has examined pain palliation of Radium-223 using standard dosing and contemporary PRO pain-assessment tools. Methods In this multicenter phase II trial, patients with Brief Pain Inventory (BPI) ≥3 were eligible for Radium-223 per its label. Primary endpoint was a 30% decrease in BPI Worst Pain from baseline to Week 8, sustained at Week 12 without escalation of medication on the World Health Organization (WHO) analgesic ladder. Secondary endpoints included changes in Brief Fatigue Inventory (BFI) Worst fatigue and BPI pain interference. If six of 27 subjects (22%) met the primary endpoint, the trial would expand by another 36 subjects. Results Twenty-nine subjects were accrued. Nine of 29 (31%) subjects met the primary endpoint, with 21 (72%) evaluable for the primary endpoint. Among responders: median worst pain declined 62% (range 36–100) at Week 8 and 63% (range 38–100) at Week 12; median reduction of pain interference with general activity and sleep at Week 12 was 62% (range 18–100) and 53% (range 8–100) respectively; median reduction in worst fatigue of 45% (range 10–85) at Week 12. Conclusions In the first prospective trial using standard Ra-223 doses, contemporary pain endpoints and PRO collection tools, Ra-223 palliated pain, reduced fatigue, and improved pain interference. The pain response rate easily exceeded the requirements for expansion to the second phase, but the trial was closed due to slow accrual.