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

NCT03909152 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 19-061
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

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

Keywords

Onapristone ER (Apristor); Oral Progesterone; Progesterone Receptor Positive (PR+); Anastrozole; 19-061

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  as determined by RECIST 1.1 response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = Complete Response + Partial Response (CR + PR)

  within 36 weeks

Study Arms (4)

PR+ Granulosa cell tumor (This Arm is CLOSED)

EXPERIMENTAL

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

PR+ Low grade serous ovarian cancer

EXPERIMENTAL

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

PR+ Endometrioid endometrial cancer

EXPERIMENTAL

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

PR+ Granulosa cell ovarian cancer

EXPERIMENTAL

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

Interventions

Onapristone ER DRUG

50 mg PO BID (with dosage adjustments) until POD, unacceptable toxicity or withdrawal of consent.

PR+ Endometrioid endometrial cancer; PR+ Granulosa cell tumor (This Arm is CLOSED); PR+ Low grade serous ovarian cancer

Onapristone ER + Anastrozole DRUG

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.

PR+ Granulosa cell ovarian cancer

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: GYN cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Context Therapeutics Inc.: collaborator

Study Sites (8)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Rockville Centre

Rockville Centre, New York, 11570, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

Anastrozole

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Rachel Grisham, MD
• Organization: Memorial Sloan Kettering Cancer Center

grishamr@mskcc.org

646-888-4653

Study Officials

• Rachel Grisham, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A non-randomized, open, multicenter phase 2 study.

Study Record Dates

• First Submitted: April 8, 2019
• First Posted: April 9, 2019
• Study Start: May 2, 2019
• Primary Completion: September 3, 2024
• Study Completion: September 3, 2024
• Last Updated: July 28, 2025
• Results First Posted: July 28, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF

Locations

US (8)