Onapristone and Anastrozole for the Treatment of Refractory Hormone Receptor Positive Endometrial Cancer

  • STATUS
    Recruiting
  • End date
    Dec 31, 2024
  • participants needed
    25
  • sponsor
    Thomas Jefferson University
Updated on 4 October 2022
paclitaxel
cancer
hysterectomy
estrogen
measurable disease
carcinoma
endocrine therapy
progesterone
metastasis
neutrophil count
carboplatin
hormone therapy
liver metastasis
tumor cells
aptt
adenocarcinoma
anticoagulant
endometrioid adenocarcinoma
clear cell adenocarcinoma
carcinosarcoma
serous adenocarcinoma
carboplatin/paclitaxel

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.

Description

PRIMARY OBJECTIVE:

I. To evaluate the activity and safety of a pure progesterone receptor (PR) antagonist, extended-release onapristone (onapristone), with anastrozole to treat women with recurrent metastatic estrogen receptor positive (ER+)/progesterone receptor positive (PR+) endometrial carcinoma.

SECONDARY OBJECTIVES:

I. To estimate the disease control rate (DCR). II. To describe duration of response (DOR). III. To evaluate the safety and tolerability. IV. To evaluate quality of life using the Edmonton Symptom Assessment questionnaire.

EXPLORATORY OBJECTIVES:

I. To characterize the ER and PR expression by immunohistochemistry (IHC) pre- and post-treatment.

II. To assess antiproliferative effect in both treatment arms using Ki-67 expression by IHC.

III. To assess phosphorylated PR (pPR) and PR target gene expressions using NanoString technology pre- and post-treatment.

IV. To assess next generation sequencing (NGS) changes pre- and post-treatment. V. To assess circulating tumor cells (CTCs) in the peripheral blood at diagnosis and at progression.

OUTLINE

Patients receive onapristone orally (PO) twice daily (BID) and anastrozole PO once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 24 cycles (24 months) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then for up to 1 year.

Details
Condition Refractory Endometrial Adenocarcinoma, Refractory Endometrial Carcinoma, Refractory Endometrial Clear Cell Adenocarcinoma, Refractory Endometrial Endometrioid 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 on4 October 2022

Eligibility

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
Clear cell adenocarcinoma
Patients with the following histologic epithelial cell types are eligible
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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