|In CARD (YouTube link) wordt onderzocht of patiënten die al abiraterone (of enzalutamide) en docetaxel hebben gehad als derde lijn nu het beste kunnen worden behandeld met Cabazitaxel of toch nog met een cross-over naar de andere androgeenblokker enzalutamide (of abiraterone). Deelnemende ziekenhuizen: RadboudUMC, Amphia, Zuyderland en ErasmusMC Kankerinstituut.
STUDY No: LPS14201
|TITLE||A randomized, open label, multicenter study of Cabazitaxel versus an AR-targeted agent (abiraterone or enzalutamide) in mCRPC patients previously treated with Docetaxel and who rapidly failed a prior AR-targeted agent (CARD)|
|PHASE OF DEVELOPMENT||Phase IV|
To compare the radiographic Progression-Free Survival (rPFS) [Using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for measurable lesions and Prostate Cancer Working Group 2 (PCWG2) criteria for bone scan lesions] (1)(2) of chemotherapy (Cabazitaxel plus prednisone) (Arm A) versus AR targeted therapy ( enzalutamide or abiraterone acetate plus prednisone) (Arm B) in mCRPC patients who have been treated with docetaxel and who had disease progression while receiving AR targeted therapy within 12 months of AR treatment initiation (≤ 12 months)(either before or after docetaxel)
To compare efficacy of cabazitaxel plus prednisone to enzalutamide or abiraterone acetate plus prednisone for:
PSA response rate
Time to PSA progression (TTPP)
Objective tumor response (RECIST1.1 criteria in patients with measurable disease)
Duration of tumor response
Pain intensity palliation
Time to pain progression
Symptomatic Skeletal Events (SSEs) rate
Time to occurrence of Symptomatic Skeletal Events (SSEs)
Overall survival (OS)
Health status/utility (EQ-5D-5L)
To evaluate the correlation of a signature of resistance to AR targeted agents with clinical outcomes, via the analysis of Circulating Tumor Cells (CTCs) phenotypes as well as expression and localization of proteins including AR isoforms in CTCs.
To evaluate safety in the 2 treatment arms.
To collect circulating free nucleic acids derived from plasma at baseline and post-treatment for future biomarker studies.
|STUDY DESIGN|| Open-label randomized phase IV study
All eligible Patients (after Abi or Enza →Doc
or Doc → Abi or Enza) are randomly assigned to either arm A or B in a 1:1 proportion by using an Interactive Voice/Web Response System (IVRS/IWRS).
Patients who rapidly failed a prior AR-targeted agent are defined as patients who have disease progression while receiving AR targeted therapy within 12 months of AR treatment initiation (≤12 months).
Each patient will be treated until radiographic disease progression, unacceptable toxicity, or patient’s refusal of further study treatment
A Steering Committee will be responsible for supervising the progress of the trial. This committee will include Study Chairmen’s and Sponsor’s representatives.
A translational Steering Committee will be responsible for supervising the biomarkers part. This committee will include Study Chairmen’s and Sponsor’s representatives.
Randomization will be stratified by: Eastern Cooperative Oncology Group (ECOG) performance status (0-1 Vs. 2), time from AR targeted agent initiation to progression (]0 ; 6 months] vs ]6 ; 12 months], timing of AR targeted agent (before Vs. after docetaxel)
SEE MORE; CARD IMAGE.