Radium-223 is indicated for pts with mCRPC with symptomatic bone metastases. Biomarkers for radium-223 treatment and its correlation with AR-V7 splice variant, are both under research. The aim of this study is to assess the activity and safety of radium-223 stratified by AR-V7 status in asymptomatic pts who have progressed while on abiraterone acetate or enzalutamide treatment.
This is a single-arm, multicenter, phase IIA clinical trial. Pts will receive radium-223 at a dose of 55 kBq per kilogram, given at 4-weeks intervals for 6 intravenous injections, until progression or unacceptable toxicity. We will screen for AR-V7 splice variant and CTCs number after inclusion, at the end of treatment and at progression. We predict that the number of AR-V7[+] pts will be 25% at inclusion. Major inclusion criteria are: (1) mCRPC according to standard Prostate Cancer Working Group (PCWG2)-2 criteria, (2) asymptomatic according to Brief Pain Inventory short form, (3) ≥24 weeks of prior treatment with abiraterone acetate or enzalutamide, (4) adequate organ function and performance status. The primary endpoint is the radiographic progression-free survival (rPFS) according to the PCWG-2 criteria. A total of 52 pts were predefined for the primary analysis using the one arm log-rank test. In both cohorts, we test the null hypothesis that true median rPFS is ≤ 3 months versus the alternative hypothesis that is ≥ 6.3 months. The one-sided type I error was 0.025 in both AR-V7 subgroups. A sample size of 13 pts is needed in the AR-V7[+] subgroup to attain 80% power. In accordance with the expected ratio between cohorts, we will include 39 pts in AR-V7[-] subgroup. The secondary objectives are to investigate the safety of the treatment, to determine the association between AR-V7 status and tumor response and to establish the relationship between circulating tumor cells number with radium-223 activity. Trial registration number is NCT03002220. Date of registration was 20/10/2016. First patient included on 20/12/2016.
Clinical trial identification
NCT03002220, Initial Release Date: 20/Oct/2016
Legal entity responsible for the study
Medica Scientia Innovation Research-MEDSIR
Bayer Hispania S.L.
M.A. Gonzalez Del Alba Baamonde: Advisory boards Bayer, Astellas, Sanofi, Janssen. Travel expenses: Astellas, Sanofi, Janssen. E. Gallardo Diaz: Advisory boards: Sanofi, Janssen, Astellas, Bayer, Roche, Pfizer. Honoraria: Astellas, Sanofi, Janssen. Travel expenses: Sanofi, Janssen, Astellas, Bayer, Pfizer. Clinical trials: Sanofi, Astellas, Bayer, Bavarian-Nordic, Roche, Pfizer. All other authors have declared no conflicts of interest.