PRIMARY OBJECTIVE:~I. To assess the objective response rate (ORR) of olaparib plus cediranib and olaparib plus ceralasertib (AZD6738) combinations in patients with advanced or metastatic breast cancer with germline BRCA (breast cancer susceptibility gene) mutations who have been previously treated with PARP inhibitors.~SECONDARY OBJECTIVES:~I. To assess the safety and tolerability of olaparib in combination with cediranib and in combination with AZD6738 in patients with advanced or metastatic breast cancer with germline BRCA mutations.~II. To assess duration of response (DOR) to treatment. III. To assess best response. IV. To estimate progression free survival (PFS).~EXPLORATORY OBJECTIVES:~I. To evaluate BRCA1 expression at baseline and on progression. II. To evaluate hypoxia markers at baseline and on progression. III. To evaluate levels of angiogenesis/ inflammatory markers including VEGF (vascular endothelial growth factor) at baseline and on progression.~IV. To evaluate novel markers of resistance and response to PARP inhibitor in baseline and upon progression of disease in tumor tissue that are identified by the investigator's basic science collaborator's ongoing studies in vitro and in vivo.~V. To evaluate circulating tumor deoxyribonucleic acid (DNA) at baseline and on progression.~OUTLINE: Patients are randomized to 1 of 2 arms.~ARM I: Patients receive olaparib orally (PO) twice daily (BID) and cediranib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.~ARM II: Patients receive olaparib PO BID on days 1-28 and ceralasertib PO QD on days 1-7. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up at 30 days.
This phase II trial studies how well olaparib with cediranib or AZD6738 works in treating patients with germline BRCA mutated breast cancer that has spread to other places in the body (advanced or metastatic). Olaparib, cediranib, and AZD6738 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.