CARD: A randomized phase 4 trial comparing cabazitaxel and an androgen receptor (AR)-targeted agent in men with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel and an alternative AR-targeted agent

Background

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.

Trial design

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

NCT02485691

Legal entity responsible for the study

Sanofi

Funding

Sanofi

Disclosure

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.