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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03909152

Collaborator

Context Therapeutics (Industry)

Enrollment

Locations

Arms

Anticipated Duration (Months)

5.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Anticipated Enrollment :

43 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A non-randomized, open, multicenter phase 2 study.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

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Apr 1, 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

response rate [within 36 weeks]
as determined by RECIST 1.1 response

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
5	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Rockville Centre	Rockville Centre	New York	United States	11570
8	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553