Extended-Release Onapristone in Treating Patients with Progesterone Receptor Positive Recurrent Ovarian, Primary Peritoneal, or Endometrial Cancer
- 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
- 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 cancer within the 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
I. To evaluate the efficacy, in terms of response rate (complete response [CR] or partial response [PR]) of onapristone extended-release (ER), as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 response within 36 weeks of treatment, in patients with progesterone receptor (PR)+ recurrent or advanced granulosa cell tumor, low grade serous ovarian cancer, or endometrioid endometrial cancer.
I. To evaluate the safety and tolerability of onapristone ER in this patient population.
II. To evaluate the duration of response, clinical benefit rate (CR, PR, stable disease [SD] lasting for >= 16 weeks) and progression free survival (PFS) of patients with PR+ recurrent or advanced low grade serous ovarian cancer, granulosa cell tumor or endometrioid endometrial cancer treated with onapristone ER.
I. To correlate the level of PR positivity (as a continuous variable) with response to therapy (defined as complete or partial response) with onapristone ER.
II. To correlate the level of phosphorylated PR (as a continuous variable) with response to therapy with onapristone ER.
III. To correlate the level of PR target gene expression (as a continuous variable) with response to therapy (defined as complete or partial response) with onapristone ER.
Patients receive extended-release onapristone orally (PO) twice daily (BID) on days 1-28. 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 and then every 3 months thereafter.
Trial Phase Phase II
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
Rachel Nicole Grisham
- Primary ID 19-061
- Secondary IDs NCI-2019-03137
- Clinicaltrials.gov ID NCT03909152