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

NCT04719273 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20P.829
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 1 year post-treatment

• Progression-Free Survival (PFS)

  4 month PFS is defined as a binary endpoint, from first dose of onapristone and anastrozole to 4 months of therapy as "confirmed progression-free" or "not progression-free" (including cancer progression or censored subjects). Will use the date of first documented disease progression or recurrence, as assessed by using RECIST 1.1 criteria, or death due to any cause, whichever occurs first.

  At 4 months

Secondary Outcomes (5)

• Disease Control Rate

  Up to 1 year post-treatment

• Time to Response

  From randomization to first documented response (CR or PR) in months, assessed up to 1 year post-treatment

• Duration of Response

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

• Type, frequency and severity of adverse events and laboratory abnormalities

  Up to 30 days post-treatment

• Quality of Life and pain score

  Up to 1 year post-treatment

Other Outcomes (1)

• Estrogen receptor and progesterone receptor expression

  Up to 1 year post-treatment

Study Arms (1)

Treatment (onapristone, anastrozole)

EXPERIMENTAL

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) until November 30, 2023 or in the absence of disease progression or unacceptable toxicity.

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)

Interventions

Extended-release Onapristone DRUG

Given PO

Also known as: ER Onapristone

Treatment (onapristone, anastrozole)

Anastrozole DRUG

Given PO

Also known as: 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

Treatment (onapristone, anastrozole)

Quality-of-Life Assessment OTHER

Ancillary studies

Treatment (onapristone, anastrozole)

Questionnaire Administration OTHER

Ancillary studies

Treatment (onapristone, anastrozole)

Estrogen Receptor Positive (Positive Estrogen Receptor; ESR Positive; ESR1 Positive; ER Positive; Estrogen Receptor Alpha Positive) DIAGNOSTIC_TEST

Immunohistochemistry (IHC):Integral : Tissue

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

Treatment (onapristone, anastrozole)

Progesterone Receptor Positive ( PGR Positive; PR Positive) DIAGNOSTIC_TEST

Immunohistochemistry (IHC)

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

Treatment (onapristone, anastrozole)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Context Therapeutics Inc.: collaborator

Study Sites (2)

Jefferson Abington Hospital

Abington, Pennsylvania, 19001, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Anastrozole

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Tommy Buchanan, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 22, 2021
• Study Start: January 28, 2021
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: January 8, 2025

Record last verified: 2025-01

Locations

US (2)