Testing the Addition of ASTX660 (Tolinapant) to the Usual Chemotherapy Treatment (Paclitaxel With or Without Bevacizumab) in Patients With Recurrent Ovarian Cancer

Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of high gradeepithelial ovarian, fallopian tube, or primary peritoneal cancer. Required:submission of pathology report

• Patients with the following histologic cell types are eligible:

• High grade serous

• Endometrioid, grade 3

• Clear cell

• Undifferentiated

• Mixed epithelial

• Carcinosarcoma

• Adenocarcinoma, not otherwise specified (NOS)

• Patients must be considered to have platinum-resistant or platinum-refractoryrecurrent ovarian cancer to be enrolled in this trial

• Platinum-resistant disease is defined as progression within < 6 months fromcompletion of platinum-based therapy. The date should be calculated from thelast administered dose of platinum therapy

• Platinum-refractory disease is defined as progression within 30 days ofcompleting the last dose of platinum during initial therapy. The date should becalculated from the last administered dose of platinum therapy

• Patients must have evaluable disease or measurable disease defined by ResponseEvaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. Measurable disease isdefined as at least one lesion that can be accurately measured in at least onedimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm whenmeasured by CT or MRI. Lymph nodes must be ≥ 15 mm in short axis when measured by CTor MRI. Previously irradiated lesions can be considered as measurable disease onlyif progressive disease has been unequivocally documented at that site sinceradiation

• Patients with treated brain metastases are eligible if follow up brain imaging aftercentral nervous system (CNS) directed therapy shows no evidence of progression

• Patients must have received ≥ 1 platinum-based therapy and not more than 5 priorlines of therapies. Notes:

• Adjuvant/neoadjuvant therapy is counted as only 1 regimen in the absence ofintervening progression.

• Maintenance therapy (e.g., bevacizumab, poly adenosine diphosphate-ribosepolymerase [PARP] inhibitor will be considered part of the preceding line oftherapy [i.e., not counted independently])

• Therapy changed due to toxicity in the absence of progression will beconsidered part of the same line (i.e., not counted independently)

• Hormonal therapy will not be counted as a separate line of therapy

• Age ≥ 18

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3

• Platelets ≥ 100,000 cells/mm^3

• Hemoglobin ≥ 8 g/dl

• Creatinine ≤ institutional upper limit of normal (ULN), OR calculated creatinineclearance (CrCL) of ≥ 50 mL/min by the Cockcroft-Gault formula

• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients withknown Gilbert's disease who have bilirubin level ≤ 3 x ULN may be enrolled)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 xinstitutional ULN

• Patients with a known history or current symptoms of cardiac disease, or history oftreatment with cardiotoxic agents, should have a clinical risk assessment of cardiacfunction using the New York Heart Association Functional Classification. To beeligible for this trial, patients should be class 2B or better

• Patients with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with the safety or efficacy assessment ofthe investigational regimen are eligible for this trial

• The patient or a legally authorized representative must provide study-specificinformed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

• No active infection requiring parental antibiotics

• No evidence of intra-abdominal abscess, abdominal/pelvic fistula, gastrointestinalperforation, gastrointestinal (GI) obstruction, and/or with drainage gastrostomytube required. NOTE: required interval since last bowel obstruction: 30 day minimumfor incomplete obstruction, resolved with conservative means; 6 months for fistula

Exclusion Criteria:

• Patients who have received prior weekly paclitaxel in a platinum-resistant setting

• Major surgical procedure within 28 days prior to registration, or anticipation ofneed for major surgical procedure during the study. Note: Placement of a vascularaccess device, thoracentesis, and/or paracentesis will not be considered majorsurgery

• Women who are pregnant or are unwilling to discontinue nursing

• Evidence of bleeding diathesis or clinically significant coagulopathy within thepast 3 months. Patients are not excluded for past or current use of anticoagulation

• Uncontrolled hypertension (systolic blood pressure [SBP] > 150 and/or diastolicblood pressure [DBP] > 90)

• Patients currently taking and unwilling/unable to discontinue the use of drugs thatare known to inhibit or induce P-glycoprotein (gp)