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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Granulosa Cell Ovarian Cancer; Low Grade Serous Ovarian/ Primary Peritoneal Cancer; Endometrioid Endometrial Cancer
• Intervention / Treatment: Drug: Onapristone ER; Drug: Onapristone ER + Anastrozole

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rockville Centre, New York, United States, 11570
      • Memorial Sloan Kettering Rockville Centre
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.
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.

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Context Therapeutics Inc.

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2019
• Primary Completion (Anticipated): April 1, 2024
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: April 8, 2019
• First Submitted That Met QC Criteria: April 8, 2019
• First Posted (Actual): April 9, 2019

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: May 1, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Onapristone ER (Apristor); Oral Progesterone; Progesterone Receptor Positive (PR+); Anastrozole; 19-061
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Endometrial Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Anastrozole; Onapristone
• Other Study ID Numbers: 19-061

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing Supporting Information Type: SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No