AzTrials
AzTrials

Refractory Endometrial AdenocarcinomaPhase 2NCT04719273

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

A Phase 2 study testing Extended-release Onapristone, Anastrozole and Quality-of-Life Assessment in people with Refractory Endometrial Adenocarcinoma and Refractory Endometrial Carcinoma, run by Thomas Jefferson University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Extended-release Onapristone, Anastrozole and Quality-of-Life Assessment
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
2 sitesUnited States
Study dates
28 Jan 2021to 17 Dec 2025
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 one prior treatment with a platinum/taxane chemotherapy regimen for management of disease
  • Patients cannot have treatment with more than 2 prior lines of therapy (one line must be platinum/taxane regimen)
  • 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 >= 15 mm in short axis when measured by CT or MRI
  • Patients with the following histologic epithelial cell types are eligible:
Show all 32Show fewer
  • 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
  • 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
  • Females are only eligible for this study if they are postmenopausal. This is defined as meeting one of the following criteria:
  • S/p total abdominal hysterectomy and bilateral salpingo-oopherectomy
  • Patients who are in menopause is defined clinically as 12 consecutive months of amenorrhea in a woman over 55 in the absence of other biological or physiological causes OR 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

Who cannot join

  • 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
  • Patient has a concurrent malignancy or history of invasive malignancy within 3 years of enrollment, with the exception of basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix that has completed curative therapy
  • 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
  • Known brain metastasis which have not been treated or showed stability for >= 6 months
Show all 13Show fewer
  • 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 greater than or equal to grade 3 severity
  • Women who are pregnant or nursing
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Jefferson Abington Hospital

    Abington, Pennsylvania, 19001

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: A Phase II Clinical Trial Evaluating the Combination of Onapristone With Anastrozole for Women With Refractory Hormone Receptor Positive Endometrial Cancer

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

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

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 every 3 months for up to 1 year after last treatment administration.

Being tested
Extended-release Onapristone, Anastrozole, Quality-of-Life Assessment, Questionnaire Administration, Estrogen Receptor Positive (Positive Estrogen Receptor; ESR Positive; ESR1 Positive; ER Positive; Estrogen Receptor Alpha Positive)
Medical subject headings
Endometrial Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Extended-release OnapristoneDrug

    Also called ER Onapristone

    Given PO

  • AnastrozoleDrug

    Also called 120511-73-1, 2,2'-[5-(1H-1,2,4-Triazol-1-ylmethyl)-1,3-phenylene]di(2-methylpropionitrile), Alpha,alpha,alpha', alpha'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-benzenediacetonitrile,, Anastrazole, Anastrozole, Anastrozole, ANASTROZOLE, anastrozole, Arimidex, ICI D1033, ICI-D1033, ZD-1033

    Given PO

  • Quality-of-Life AssessmentOther

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • Estrogen Receptor Positive (Positive Estrogen Receptor; ESR Positive; ESR1 Positive; ER Positive; Estrogen Receptor Alpha Positive)Diagnostic test

    Also called Level/Quantity, Other: Greater than or equal to 1 percent

    Immunohistochemistry (IHC):Integral : Tissue

  • Progesterone Receptor Positive ( PGR Positive; PR Positive)Diagnostic test

    Also called Level/Quantity, Other: Greater than or equal to 1 percent

    Immunohistochemistry (IHC)

Study groups in NCT04719273
Study groupRoleWhat they receive
Treatment (onapristone, anastrozole)ExperimentalPatients receive onapristone PO BID and anastrozole PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles (24 months) until November 30, 2023 or in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Extended-release Onapristone; Drug: Anastrozole; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Diagnostic Test: Estrogen Receptor Positive (Positive Estrogen Receptor; ESR Positive; ESR1 Positive; ER Positive; Estrogen Receptor Alpha Positive); Diagnostic Test: Progesterone Receptor Positive ( PGR Positive; PR Positive)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR)

    Defined by the percentage of patients with tumor response (complete response [CR] or partial response [PR]) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Up to 1 year post-treatment, up to 36 months total

  2. Progression-Free Survival (PFS)

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: From treatment until disease progression or death, up to 25 months

Secondary outcomes (5)

  1. Disease Control Rate

    Defined as best overall response of CR, PR, or stable disease lasting for >= 24 weeks, per RECIST 1.1.

    Measured: Up to 1 year post-treatment

  2. Time to Response

    Time to Response defined as time from randomization to first documented response (CR or PR) in months.

    Measured: up to 1 yr post treatment

  3. Duration of Response in Participants With Complete Response

    Duration of Response (DOR) is the time from the first documented achievement of a Partial Response (PR) or Complete Response (CR) until the date of confirmed disease Progression (PD) or death due to endometrial cancer.

    Measured: From the first date of documented response to progression or death due to endometrial cancer, assessed up to 1 year post-treatment

  4. Duration of Response in Participants With Partial Response

    Duration of Response (DOR) is the time from the first documented achievement of a Partial Response (PR) or Complete Response (CR) until the date of confirmed disease Progression (PD) or death due to endometrial cancer.

    Measured: From the first date of documented response to progression or death due to endometrial cancer, assessed up to 1 year post-treatment

  5. Quality of Life Assessed by the Edmonton Symptom Assessment System

    Quality of life and pain scores are defined by the Edmonton Symptom Assessment System (ESAS) using nine subjective patient measures of well-being including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, shortness of breath. Numerical Rating Scale (NRS): Each symptom, including Pain and Well-being (which reflects Quality of Life), is rated on a 0 to 10 scale. Pain Score: 0 = No pain, 10 = Worst possible pain. Quality of Life / Well-being Score: 0 = Best possible feeling of well-being (i.e., best QoL), 10 = Worst possible feeling of well-being (i.e., worst QoL). ESAS scores were collected over the course of treatment and follow-up. Results represent the mean score for each symptom averaged across all available assessments for each participant. Higher scores reflect greater symptom severity. Scores are reported as means with standard deviations.

    Measured: Up to 25 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jan 2021
  2. Study start28 Jan 2021
  3. Primary completion1 Mar 2025
  4. Study completion17 Dec 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04719273
Sponsor's protocol ID
20P.829
Other IDs
JT 15031
Status last verified
Jul 2026
First submitted
4 Jan 2021
Last updated
17 Jul 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in