Extended-Release Onapristone with or without Anastrozole in Treating Patients with Progesterone Receptor Positive Recurrent Ovarian, Primary Peritoneal, or Endometrial Cancer

Inclusion Criteria

• Histologically confirmed diagnosis at Memorial Sloan Kettering (MSK) of either (1) granulosa cell ovarian cancer, (2) low grade serous ovarian/ primary peritoneal cancer, or (3) endometrioid endometrial cancer; with PR expression >= 1% by immunohistochemistry (IHC) on archival tissue taken within the prior 3 years or new biopsy if no archival tissue is available. IHC results do not have to be from MSK
• Measurable disease as defined by RECIST 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension. Each lesion must be >= 10 mm when measured by computed tomography (CT) or magnetic resonance imaging (MRI). Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
• Patients must have had one prior chemotherapy regimen for management of disease. Note: additional lines of chemotherapy, biologic or immunotherapy are allowed
• Recovery from effects of recent surgery, radiotherapy, or chemotherapy * At least 4 weeks out from their last dose of radiation therapy * At least 4 weeks post-op from any major surgical procedure * At least 3 weeks out from their last dose of chemotherapy and/or biologic/targeted therapy
• Karnofsky performance status (KPS) of >= 70%
• Women of child-bearing potential must have a negative pregnancy test within 14 days prior to commencement of study treatment
• Women of child bearing potential must use an effective form of contraception during study and for at least 6 months after completion of study treatment
• Absolute neutrophil count (ANC) >= 1,000/mcL (performed within 14 days prior to initiation of study drug)
• Platelets >= 75,000/mcL (performed within 14 days prior to initiation of study drug)
• Hemoglobin >= 8 g/dL (performed within 14 days prior to initiation of study drug)
• Creatinine =< 1.5 x upper limit of normal (ULN) (performed within 14 days prior to initiation of study drug)
• Bilirubin =< 1.5 x ULN (performed within 14 days prior to initiation of study drug)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (performed within 14 days prior to initiation of study drug)
• Resolution of all acute toxic effects of prior therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) grade =< 1, with the exception of unresolved grade 2 neuropathy and grade 2 alopecia, which are allowed
• Patient has recovered from any prior radiotherapy
• Patients must be able to swallow tablets whole, without crushing

Exclusion Criteria

• History of another invasive malignancy (other than non-melanoma skin cancer or curatively treated in situ carcinoma) with evidence of disease within the past 3 years
• History of prior hormonal therapy (i.e., megestrol acetate, tamoxifen or aromatase inhibitors) for treatment of cancer within 28 days before starting study drug
• Any psychological, familial, sociological or geographic condition that would potentially hamper compliance with the study protocol
• Known brain metastasis which have not been treated or showed stability for >= 6 months
• Patient has received an oral or intravenous (IV) corticosteroid within the prior 28 days and requires chronic corticosteroid therapy (excludes use of steroid premeds for CT allergy)
• Uncontrolled hypertension (systolic blood pressure [BP] >= 160 mmHg or diastolic BP >= 95 mmHg) despite medical treatment. Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
• Clinically significant heart disease as evidenced by myocardial infarction or arterial thrombotic event within the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) class II-IV heart disease or cardiac ejection fraction measurement of < 50% at baseline
• Refractory nausea and vomiting, requirement for parenteral hydration and/or nutrition, drainage gastrostomy tube, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate study drug absorption
• Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study
• Use of any prescription medication during the prior 28 days of first onapristone dosing that the investigator judges is likely to interfere with onapristone activity; specifically strong inhibitors or inducers, or sensitive substrates of cytochrome P450 CYP3A4