A Study of Onapristone ER Alone Or In Combination With Anastrozole in Gynecologic Cancers That Respond to Progesterone

Study Overview
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Brief Summary
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The purpose of this study is to test any good and bad effect of the study drug, onapristone extended-release (ER) alone and in combination with anastrozole.

Official Title
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Basket Study of the Oral Progesterone Antagonist Onapristone ER (Apristor), Alone or In Combination With Anastrozole in Women With Progesterone Receptor Positive (PR+) Recurrent Granulosa Cell Tumor, Low Grade Serous Ovarian Cancer or Endometrioid Endometrial Cancer

Conditions
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Granulosa Cell Ovarian Cancer, Low Grade Serous Ovarian/ Primary Peritoneal Cancer, Endometrioid Endometrial Cancer

Intervention / Treatment
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* Drug: Onapristone ER
* Drug: Onapristone ER + Anastrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis at 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 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 ≥10mm when measured by CT or MRI. Lymph nodes must be ≥15mm 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 Must be ≥ 18 years of age 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 Laboratory Test Findings performed within 14 days prior to initiation of study drug showing: Bone marrow function: Absolute neutrophil count (ANC) ≥ 1,000/mcL Platelets ≥ 75,000/mcL Hemoglobin ≥ 8 g/dL Renal function: °Creatinine ≤ 1.5 x ULN Hepatic function: Bilirubin ≤ 1.5 x ULN AST and ALT ≤ 2.5 x ULN Resolution of all acute toxic effects of prior therapy to NCI 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., megesterol 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 IV corticosteroid within the prior 28 days and requires chronic corticosteroid therapy (excludes use of steroid premeds for CT allergy) Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95mmHg) 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. Investigators should consult the following table of clinically-relevant products http://medicine.iupui.edu/CLINPHARM/ddis/clinical-table.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A non-randomized, open, multicenter phase 2 study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PR+ Granulosa cell tumor (This Arm is CLOSED)<br>Enrolled patients will initiate treatment with onapristone ER 50 mg by mouth twice daily, about 12 hours apart, beginning Day 1 of Cycle 1. A Cycle is 28 days. This Arm is CLOSED. | Drug: Onapristone ER<br>* 50 mg PO BID (with dosage adjustments) until POD, unacceptable toxicity or withdrawal of consent.<br>|
| Experimental: PR+ Low grade serous ovarian cancer<br>Enrolled patients will initiate treatment with onapristone ER 50 mg by mouth twice daily, about 12 hours apart, beginning Day 1 of Cycle 1. A Cycle is 28 days | Drug: Onapristone ER<br>* 50 mg PO BID (with dosage adjustments) until POD, unacceptable toxicity or withdrawal of consent.<br>|
| Experimental: PR+ Endometrioid endometrial cancer<br>Enrolled patients will initiate treatment with onapristone ER 50 mg by mouth twice daily, about 12 hours apart, beginning Day 1 of Cycle 1. A Cycle is 28 days | Drug: Onapristone ER<br>* 50 mg PO BID (with dosage adjustments) until POD, unacceptable toxicity or withdrawal of consent.<br>|
| Experimental: PR+ Granulosa cell ovarian cancer<br>Enrolled patients will initiate treatment with onapristone ER 50 mg by mouth twice daily, about 12 hours apart and anastrozole 1mg po QD in AM beginning Day 1 of Cycle 1. A Cycle is 28 days. | Drug: Onapristone ER + Anastrozole<br>* Onapristone ER Patients will take 50 PO BID in the form of two 20 mg tablets and one 10 mg tablet taken with food and water twice daily. Patients will be prescribed anastrozole 1mg PO QD. Anastrozole will be taken once daily in the AM with patients morning dose of onapristone ER.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate | as determined by RECIST 1.1 response | within 36 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Onapristone ER (Apristor), Oral Progesterone, Progesterone Receptor Positive (PR+), Anastrozole, 19-061