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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2

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

Treatments: Drug: Onapristone ER; Drug: Onapristone ER + Anastrozole

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03909152

19-061

Details and patient eligibility

About

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.

Enrollment: 34 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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34 participants in 4 patient groups

PR+ Granulosa cell tumor (This Arm is CLOSED)

Experimental group

Description:

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.

Treatment:

Drug: Onapristone ER

PR+ Low grade serous ovarian cancer

Experimental group

Description:

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

Treatment:

Drug: Onapristone ER

PR+ Endometrioid endometrial cancer

Experimental group

Description:

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

Treatment:

Drug: Onapristone ER

PR+ Granulosa cell ovarian cancer

Experimental group

Description:

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.

Treatment:

Drug: Onapristone ER + Anastrozole