PERSONALIZED MEDICINE GROUP / UCBG UC-0105/1304: SAFIR02_Breast - Evaluation of the Efficacy of High Throughput Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer

Brief Summary

Detailed Description

Screening phase: New frozen biopsy or an archived frozen sample or ctDNA sample will be sent to the genomic platforms for DNA extraction and genomic analysis (DNA microarrays and Next generation sequencing). Patients can be considered as pre-eligible for the targeted substudy 1 randomisation phase when both following mandatory conditions have been met: stable or responding disease has been observed (investigator judgment) after 6 to 8 cycles of chemotherapy (or at least after 4 cycles of chemotherapy if stopped for toxicity) and targetable alteration has been identified by the Molecular Tumor Board (MTB). If not eligible for the substudy 1 randomisation phase, patients can be considered as pre-eligible for the immune substudy 2 randomization phase when both following mandatory conditions are met: stable or responding disease (investigator judgment) is observed after 6 to 8 cycles of chemotherapy (or at least after 4 cycles if treatment was stopped due to toxicity) AND not eligible to randomization in the substudy 1 (because patient had no targetable alteration identified by the Molecular Tumor Board, or failed to have a genomic profile for the tumor \[low tumor cells percentage, technical issue during genomic analysis, etc.\], or a non inclusion criteria that precluded entry into the substudy 1) Randomization phase: The mandatory post-chemotherapy wash-out period, of 28 days for 21 or 28 day-cycle chemotherapies or of 15 days for weekly (except monoclonal antibodies) or daily chemotherapies,will provide time to achieve all the required tests and examinations. The randomization program will allocate the following treatments with a 2:1 ratio in favor of Arm A of the considered substudy: Substudy 1 : targeted therapies versus standard maintenance chemotherapy * Arm A1 / targeted arm: targeted maintenance from a list of 8 targeted drugs guided by the genomic analysis, or * Arm B1 / chemotherapy arm : maintenance chemotherapy (or no antineoplastic treatment in case of toxicity at the time of randomization) Substudy 2 : immunotherapy versus standard maintenance chemotherapy * Arm A2 / immunotherapy maintenance arm: MEDI4736 or * Arm B2 / chemotherapy arm: chemotherapy continued as a maintenance chemotherapy (or no antineoplastic treatment in case of toxicity)

Primary Outcomes

Secondary Outcomes

• overall response rates and changes in tumor size in each substudy(tumor response is assessed every 21 days from treatment initiation until first progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months))
• overall survival in each substudy(from randomization to death (any cause), up to 16 months)
• efficacy (response rate, change in tumor size, progression-free survival, overall survival) and safety of each individual targeted agent (substudy 1)(tumor response is assessed every 21 days from treatment initiation until first progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months))
• correlate molecular characteristics in patients with the efficacy endpoints (response rate, progression-free and overall survival) in each substudy(from randomization or treatment initiation to disease progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months))
• progression-free survival in patients treated with anti-PDL1 antibody (MEDI4736) compared to standard maintenance therapy arm(from randomization to disease progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months))
• evaluate safety, in each substudy(toxicities will be assessed during the whole treatment period (4 months expected in average) followed by a 1-year post-treatment follow-up period, and reported during the visits scheduled by the study flow chart)