Adavosertib With or Without Olaparib in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

PRIMARY OBJECTIVE: I. To determine the objective response rate (ORR) as determined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) of adavosertib (AZD1775) alone or in combination with olaparib in women with recurrent ovarian cancer in whom progression has been documented following poly ADP‐ribose polymerase (PARP) inhibitor therapy. SECONDARY OBJECTIVES: I. To evaluate the overall safety and tolerability of AZD1775 alone or in combination with olaparib in this population. II. To evaluate the disease control rate (DCR) = overall response rate (ORR) plus stable disease rate for 16 weeks. III. To evaluate the progression free survival (PFS) and overall survival (OS) of this population following AZD1775 alone or in combination with olaparib. IV. To evaluate the duration of response by RECIST version (v)1.1. EXPLORATORY OBJECTIVES: I. To evaluate the efficacy of each arm by BRCA‐mutation status (BRCA‐mt) and homologous recombination deoxyribonucleic acid (DNA) repair deficiencies (HRD). II. To describe endogenous and dynamic markers of DNA damage response in tumor tissue and circulating surrogates, such as circulating tumor cells (CTC), circulating tumor DNA (ctDNA), exosomes (cellular/nuclear), cell cycle kinetics (CDKs), and immunophenotype. III. To examine genomic alterations associated with response and mechanisms of resistance to olaparib and/or AZD1775. OUTLINE: Patients are randomized to 1 of 2 arms. If enrollment pauses for 1 arm, patients will be assigned to the enrolling arm. Study has a new arm 3 and enrolling patients. ARM I: Patients receive adavosertib orally (PO) once daily (QD) on days 1‐5 and 8‐12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive olaparib PO twice daily (BID) on days 1‐21 and adavosertib PO QD on days 1‐3 and 8‐10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm III: Patient receive ceralasertib tablets by PO BID each day on Days 1‐14. You will also take olaparib tablets by PO BID each day on Days 1‐28. After completion of study treatment, patients are followed up for 30 days and periodically afterwards.