mCRPC is highly heterogeneous with coexistence of AR-dependent and AR-independent tumor clones. New AR-targeted agents (abiraterone acetate, enzalutamide) and taxanes (docetaxel (DOC), cabazitaxel - specifically developed to overcome DOC resistance) are the backbone of mCRPC therapy. The rising concern of cross-resistance between mCRPC therapies and the evidence that some patients may not respond to all available drugs have increased the complexity of managing mCRPC. There is thus a need to design trials helping to define the optimal sequence of therapies to optimize patient outcomes.
CARD is a randomized phase 4 trial involving 79 sites in 12 European countries. A total of 324 patients with mCRPC previously treated with DOC and who failed a prior AR-targeted agent (abiraterone acetate or enzalutamide, either before or after DOC) within 12 months of AR-targeted treatment initiation will be randomized (1:1) to receive cabazitaxel (25mg/m2 every 3 weeks plus daily prednisone and prophylactic G-CSF) or the alternative AR-targeted agent until radiographic progression, unacceptable toxicity or patient's request. Randomization will be stratified by ECOG performance status (0-1 vs. 2), time to progression with prior AR-targeted agent (
Clinical trial identification
Legal entity responsible for the study
R. de Wit: Research grant from Sanofi International coordinator of CARD study Consulting fees from Sanofi.
R. de Wit: Research grant from Sanofi. Consulting fee from Sanofi CARD investigator and Steering committee member.
K. Fizazi: Paid advisor at Sanofi advisory boards Investigator and steering committee member for CARD study.
E. Efstathiou: Research grant from Sanofi. Paid advisor at Sanof advisory boards. Investigator and steering Committee member of CARD study.
R. Dittamore: Employee of Epic Sciences, Inc., La Jolla, USA.
S. Hitier: CARD statistician - Employee of Sanofi.
K. Pantel: Member of CARD translational steering committee.
C. Sternberg: Investigator and steering committee member of CARD study. Consulting fee from Sanofi
B. Tombal: Paid advisor by Sanofi Investigator and Steering Committee member of CARD study.
C. Wülfing: Investigator and steering committee member of CARD study.
J. de Bono: Johann de Bono served on Sanofi advisory boards as a paid advisor. He is also investigator and member of CARD Steering committee.