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

• ClinicalTrials.gov Identifier: NCT03909152
• Recruitment Status: Active, not recruiting
• First Posted: April 9, 2019
• Last Update Posted: May 3, 2023
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborator: Context Therapeutics Inc.
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Granulosa Cell Ovarian Cancer; Low Grade Serous Ovarian/ Primary Peritoneal Cancer; Endometrioid Endometrial Cancer	Drug: Onapristone ER; Drug: Onapristone ER + Anastrozole	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A non-randomized, open, multicenter phase 2 study.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 2, 2019
• Estimated Primary Completion Date: April 2024
• Estimated Study Completion Date: April 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: PR+ Granulosa cell tumor (This Arm is CLOSED); 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; 50 mg PO BID (with dosage adjustments) until POD, unacceptable toxicity or withdrawal of consent.
Experimental: PR+ Low grade serous ovarian cancer; 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; 50 mg PO BID (with dosage adjustments) until POD, unacceptable toxicity or withdrawal of consent.
Experimental: PR+ Endometrioid endometrial cancer; 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; 50 mg PO BID (with dosage adjustments) until POD, unacceptable toxicity or withdrawal of consent.
Experimental: PR+ Granulosa cell ovarian cancer; 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; 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.

Outcome Measures

Primary Outcome Measures :

1. response rate [ Time Frame: within 36 weeks ]
   as determined by RECIST 1.1 response

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: GYN cancer
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, New Jersey

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States, 07920

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States, 07748

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States, 07645

United States, New York

Memorial Sloan Kettering Commack

Commack, New York, United States, 11725

Memorial Sloan Kettering Westchester

Harrison, New York, United States, 10604

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

Memorial Sloan Kettering Rockville Centre

Rockville Centre, New York, United States, 11570

Memorial Sloan Kettering Nassau

Uniondale, New York, United States, 11553

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Context Therapeutics Inc.

Investigators

• Principal Investigator: Rachel Grisham, MD; Memorial Sloan Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan Kettering Cancer Center 

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT03909152
• Other Study ID Numbers: 19-061
• First Posted: April 9, 2019
• Last Update Posted: May 3, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
• Supporting Materials: Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:

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

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Endometrial Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Uterine Neoplasms; Uterine Diseases; Anastrozole; Onapristone; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action