Onapristone and Anastrozole in Refractory Estrogen and Progesterone Positive Endometrial Cancer

  • End date
    Dec 15, 2023
  • participants needed
  • sponsor
    Thomas Jefferson University
Updated on 12 June 2021
measurable disease
endocrine therapy
neutrophil count
hormone therapy
liver metastasis
tumor cells
endometrioid adenocarcinoma
clear cell adenocarcinoma
serous adenocarcinoma


This phase II trial studies the effect of onapristone and anastrozole in treating patients with hormone receptor positive endometrial cancer that has not responded to previous treatment (refractory). Progesterone and estrogen are hormones that can cause the growth of endometrial cancer cells. Onapristone blocks the use of progesterone by the tumor cells. Anastrozole is a drug that blocks the production of estrogen in the body. Giving onapristone with anastrozole may work better than anastrozole alone in treating patients with hormone receptor positive endometrial cancer.


Endometrial cancer is the most common gynecologic malignancy in the United States with an incidence that continues to increase each year. More than 60,000 women were diagnosed with endometrial cancer in 2018 and this disease contributes to more than 10,000 deaths annually. Unopposed estrogen production and obesity are the most common risk factors for the development of endometrial cancer; both late stage disease and histologic subtype portends to a poor prognosis with a five-year survival of only 20%. In the second line setting, cytotoxic chemotherapy has a 13% response rate and hormonal therapy with anastrozole has a response rate of 9%. For a minority of patients with MSI-high endometrial cancer (about 30% of patients), pembrolizumab is a therapeutic option and results in an overall response rate of 39% in 149 patients across 15 tumor types with 78% of responses lasting greater than 6 months and has led to FDA approval of this single agent in tissue agnostic cases. Megesterol acetate is approved in the second line setting with response rates as high as 24% in conjunction with tamoxifen, but is not commonly used due to poor tolerance and high risk of thrombosis. The majority of patients with recurrent endometrial cancer have limited therapeutic options and the development of second line therapies that result in improved response is an unmet clinical need. Using targeted hormonal treatment may present potential opportunities for improved treatment outcomes for these women.

Condition Endometrial Carcinoma, Uterine Cancer, Endometrial Cancer, Refractory Endometrial Carcinoma, Refractory Endometrial Endometrioid Adenocarcinoma, Refractory Endometrial Adenocarcinoma, Refractory Endometrial Clear Cell Adenocarcinoma, Refractory Endometrial Mixed Cell Adenocarcinoma, Refractory Endometrial Serous Adenocarcinoma, Refractory Endometrial Undifferentiated Carcinoma
Treatment questionnaire administration, quality-of-life assessment, anastrozole, Anastrozole 1mg, Onapristone, Extended-Release Formulation, Extended-release Onapristone
Clinical Study IdentifierNCT04719273
SponsorThomas Jefferson University
Last Modified on12 June 2021


Yes No Not Sure

Inclusion Criteria

Age greater than or equal to 18 years old
Endometrioid adenocarcinoma
Histologically confirmed diagnosis of endometrial cancer with ER and/or 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 Thomas Jefferson University
Serous adenocarcinoma
Patients who have failed front line therapy with carboplatin/paclitaxel
Undifferentiated carcinoma
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.)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 >= 10 mm when measured by computed tomography (CT) or magnetic resonance imaging (MRI). Lymph nodes must be >= 10 mm in short axis when measured by CT or MRI
Patients with the following histologic epithelial cell types are eligible
Clear cell adenocarcinoma
Mixed epithelial carcinoma
Adenocarcinoma not otherwise specified (NOS)
They cannot receive chemotherapy, immunotherapy or other endocrine therapy concurrently
Please note: patients with carcinosarcoma are ineligible for this trial
Patients must have had one prior treatment with a platinum/taxane chemotherapy regimen for management of disease
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Hemoglobin 9 g/dl or more
Must have a life expectancy of at least 12 weeks as judged by the treating physician
Postmenopausal females are only eligible for this study. This is defined as being status post (s/p) hysterectomy or patients who are in menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
Body weight > 30 kg
Absolute neutrophil count 1500/ul or more
Platelets 100,000/ul or more
Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin < 3 mg/dl)
Endocrine and targeted therapy protocols usually enroll patients with aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN) in patients without underlying liver metastasis and < 5.0 x ULN in patients with underlying liver metastasis
Glomerular filtration rate (GFR) greater than or equal to 40 ml/min using the Cockcroft-Gault formula or measured creatinine clearance using 24 hours urine collection
International normalized ratio (INR) OR prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
All subjects must be able to comprehend and sign a written informed consent document
Resolution of all acute toxic effects of prior therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (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
Be able to read and speak English

Exclusion Criteria

Concurrent or recent chemotherapy, radiotherapy, immunotherapy, or general anesthesia/major surgery within 3 weeks
History of prior hormonal therapy (i.e., megestrol acetate, tamoxifen or aromatase inhibitors) for treatment cancer within the past 2 months. Other concurrent hormonal therapy will not be allowed on this trial
Patients with concurrent second malignancy (other than non-melanoma skin cancer or curatively treated in situ carcinoma)
Patients must have recovered from all known or expected toxicities from previous treatment and passed a treatment-free "washout" period of 3 weeks before starting this program. However, grade 1 or 2 neuropathy and alopecia are acceptable
If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
Has received prior systemic anti-cancer therapy including investigational agents within 3 weeks prior to randomization
Participants must have recovered from all adverse events (AEs) due to previous therapies to =< grade 1 or baseline. Participants with =< grade 2 neuropathy may be eligible
Known brain metastasis which have not been treated or showed stability for >= 6 months
Proteinuria > 1+ on urinalysis or > 1 gm/24 hours (hr)
Known history of New York Heart Association stage 3 or 4 cardiac disease
A pleural or pericardial effusion of moderate severity or worse
Women who are pregnant or nursing
Women who are pre-menopausal
Has an active infection requiring systemic therapy
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
Patients may not be on a concurrent clinical trial, unless approved by investigator
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