Brief Title
Onapristone and Anastrozole for the Treatment of Refractory Hormone Receptor Positive Endometrial Cancer
Official Title
A Phase II Clinical Trial Evaluating the Combination of Onapristone With Anastrozole for Women With Refractory Hormone Receptor Positive Endometrial Cancer
Brief 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.
Detailed 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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Objective response rate (ORR)
Secondary Outcome
Disease Control Rate
Condition
Refractory Endometrial Adenocarcinoma
Intervention
Extended-release Onapristone
Study Arms / Comparison Groups
Treatment (onapristone, anastrozole)
Description: Patients receive onapristone PO BID and anastrozole PO 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
25
Start Date
January 28, 2021
Completion Date
December 31, 2024
Primary Completion Date
December 31, 2024
Eligibility 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
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, 215-955-8874, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04719273
Organization ID
20P.829
Secondary IDs
P30CA056036
Responsible Party
Sponsor
Study Sponsor
Thomas Jefferson University
Collaborators
National Cancer Institute (NCI)
Study Sponsor
, ,
Verification Date
July 2022