ESMO 2017: A Phase II Clinical Trial of Radium-223 Activity in Patients with mCRPC with Asymptomatic Progression While on Abiraterone Acetate or Enzalutamide Besides AR-V7 Mutational Status (EXCAAPE)

Madrid, Spain (UroToday.com) Dr. Joan Carles Galceran and colleagues presented their phase II trial design for assessing radium-223 activity in patients with metastatic castration-resistant prostate cancer (mCRPC) with asymptomatic progression while on abiraterone or enzalutamide. Based on results of the ALSYMPCA phase III trial [1] radium-223 is indicated for patients with mCRPC and symptomatic bone metastases. Since then, biomarkers for radium-223 treatment and its correlation with the 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 patients with mCRPC who have progressed while on abiraterone acetate or enzalutamide treatment. 

Trial design: This trial is a single-arm, multicenter, phase IIA clinical trial. Patients will receive radium-223 at a dose of 55 kBq per kilogram, given at 4-week intervals for 6 intravenous injections, or until progression or unacceptable toxicity. Patients will be screened for AR-V7 splice variant and circulating tumor cell (CTC) number after inclusion, at the end of treatment and at disease progression. The authors predict that the number of AR-V7[+] pts will be 25% at study inclusion. The major inclusion criteria are for the trial are: (i) mCRPC according to standard Prostate Cancer Working Group (PCWG2)-2 criteria, (ii) asymptomatic disease according to Brief Pain Inventory short form, (iii) ≥24 weeks of prior treatment with abiraterone acetate or enzalutamide, (iv) adequate organ function and performance status. The primary endpoint is radiographic progression-free survival (rPFS) according to the PCWG-2 criteria. Secondary outcomes include (i) investigation of treatment safety, (ii) to determine the association between AR-V7 status and tumor response, and (iii) to establish the relationship between CTC number with radium-223 activity.  A sample size of 52 patients was predefined for the primary analysis using the one arm log-rank test. The null hypothesis is that the true median rPFS is ≤ 3 months versus the alternative hypothesis of ≥ 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, the authors will include 39 pts in AR-V7[-] subgroup. The date of trial registration was October 20, 2016 and the first patient, first visit was December 20, 2016. Clinical trial identification: NCT03002220 

Speaker: Joan Carles Galceran, Vall d’Hebron University Hospital, Barcelona, Spain

Co-Authors: T. Bonfill Abella (Sabadell, Spain) P. Borrega (Cáceres, Spain) R. Collado (Cáceres, Spain) J. Garde (Barcelona, Spain) M. Gonzalez Del Alba Baamonde (Palma de Mallorca, Spain) E. Grande Pulido (Madrid, Spain) B. Mellado (Barcelona, Spain) M. Mendez Vidal (Cordoba, Spain) J. Piulats Rodriguez (Barcelona, Spain) R. Morales Barrera (Barcelona, Spain) E. Gallardo Diaz (Sabadell, Spain) P. Paredes (Barcelona, Spain) C. Suarez Rodriguez (Barcelona, Spain) O. Reig (Barcelona, Spain)S. Vazquez Estevez (Lugo, Spain)

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain

References: 

1. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369(3):213-223.
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