Trial Design: The EORTC 1333-GUCG study will run in 51 sites (21 currently activate) across seven European countries, four sites in US and 12 sites in Canada. The study is an intergroup initiative between EORTC (Coordinating Group), UNICANCER, Cancer Trials Ireland, ACCRU (United States), and CUOG (Canada). The main inclusion criteria are: (i) asymptomatic or mildly symptomatic (defined as no opioids and BPI-SF question 3 < 4), and (ii) metastases to the bone with ≥ 2 bone metastases with or without additional lymph node metastases. The main exclusion criteria is visceral metastases. The study will be powered to test for an increase of 8 months in median rPFS1 for the combination arm compared to the enzalutamide alone arm (ie. an increase from 17 months based on PREVAIL  to 25 months, HR=0.68) with a 1-sided 0.025 significance level of 90% power, resulting in 560 patients targeted for recruitment. These patients will be randomized in a 1:1 ratio to receive enzalutamide 160 mg daily or enzalutamide at the same dose and Ra-223 at 55 kBq/kg IV monthly for 6 months. Patients will be stratified by country, pain (BPI 0-1 vs BPI 2-3), prior docetaxel use (no vs yes) and use of bone targeting agents (no vs yes). The primary endpoint is radiological progression-free survival (rPFS), according to PCWG3 criteria. Secondary endpoints include prostate cancer-specific survival, overall survival, first symptomatic skeletal event (SSE), time to initiation of next systemic anti-neoplastic therapy, time to pain progression, and health-related quality of life (EQ-5D-5L and BPI).
Clinical trial information: NCT02194842
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.
2. Gillessen S, Attard G, Beer TM, et al. Management of patients with advanced prostate cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017. Eur Urol 2017 [Epub ahead of print].
3. Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 2014;371(5):424-433.
Presented by: Bertrand Tombal, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Co-Authors: Yohann Loriot, Fred Saad, Raymond S. McDermott, Sandrine Marreaud, Laurence Collette, Silke Gillessen
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA