Onapristone and Anastrozole in Refractory Estrogen and Progesterone Positive Endometrial Cancer

• Status: Recruiting
• Trial end date: 2023-12-15
• Target enrollment: 0
• Participant gender: Female

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Thomas Jefferson University
• Treatments: Anastrozole; Onapristone

Criteria

Inclusion Criteria:

• Age greater than or equal to 18 years old

• 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

• Patients who have failed front line therapy with carboplatin/paclitaxel

• 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:

• Endometrioid adenocarcinoma

• Serous adenocarcinoma

• Undifferentiated carcinoma

• Clear cell adenocarcinoma

• Mixed epithelial carcinoma

• Adenocarcinoma not otherwise specified (NOS)

• 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

• They cannot receive chemotherapy, immunotherapy or other endocrine therapy concurrently

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• 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

• Hemoglobin 9 g/dl 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