Study of Elacestrant in Combination With Onapristone in Patients With Advanced or Metastatic Breast Cancer

NCT05618613 | Terminated Phase 1 FDA Drug

• 1 other identifier: ONA-XR-103
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

Brief Summary

This is a multicenter, Phase 1b-2 study of elacestrant in combination with onapristone in patients with advanced/metastatic ER+/PgR+/HER2- breast cancer.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Determine the recommended Phase 2 dose (RP2D) of the combination of onapristone and elacestrant (Phase 1).

  9 months

• Evaluate the efficacy of elacestrant in combination with onapristone in terms of objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1 (Phase 2).

  Proportion of patients achieving a best overall response of confirmed partial or complete response (PR+CR).

  1.5 years

Secondary Outcomes (13)

• Characterize the AEs of elacestrant in combination with onapristone.

  21 months

• Characterize the serious adverse events (SAEs) of elacestrant in combination with onapristone.

  21 months

• Characterize the safety in terms of changes in clinical laboratory values of elacestrant in combination with onapristone.

  21 months

• Characterize the safety in terms of changes in vital sign measurements of elacestrant in combination with onapristone.

  21 months

• Characterize the safety in terms of changes in ECG parameters of elacestrant in combination with onapristone.

  21 months

Study Arms (1)

Elacestrant / Onapristone

EXPERIMENTAL

Elacestrant and Onapristone combination

Drug: Elacestrant; Drug: Onapristone

Interventions

Elacestrant DRUG

Elacestrant 200mg, 300mg, or 400mg once daily oral dosing in cycles of 28 days.

Also known as: RAD1901

Elacestrant / Onapristone

Onapristone DRUG

Onapristone 40mg or 50mg twice daily oral dosing in cycles of 28 days.

Elacestrant / Onapristone

Eligibility Criteria

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

You may qualify if:

• Women or men aged ≥18 years, at the time of informed consent signature. Note: Pre- and peri-menopausal women must receive goserelin for at least one month prior to initiating trial therapy, during the trial, and for at least one month after end of trial therapy. Men must receive triptorelin for at least one month prior to initiating trial therapy, during the trial and for at least one month after end of trial therapy.
• Histopathologically or cytologically confirmed ER+, PgR+, HER2-, breast cancer, per local laboratory, as per the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines (Allison et al, 2020). Note: In the context of this trial, ER and PgR status will be considered positive if ≥10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry.
• At least one measurable lesion as per RECIST version 1.1. Note: Patients with stable brain or subdural metastases are allowed if the patient has completed local therapy and has discontinued the use of corticosteroids for at least 4 weeks before starting treatment in this study. Any signs (e.g., radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
• Prior therapy with an aromatase inhibitor or fulvestrant + a CDK4/6 inhibitor in the metastatic setting or in the adjuvant setting if within 12 months of last dose of adjuvant therapy. Note: Prior therapy with everolimus is allowed.
• ECOG performance status of 0 or 1.
• Patient has adequate bone marrow and organ function, as defined by the following laboratory values:
• Absolute neutrophil count (ANC) ≥1.5 × 109/L,
• Platelets ≥100 × 109/L,
• Hemoglobin ≥9.0 g/dL,
• Potassium, sodium, calcium (corrected for serum albumin), and magnesium CTCAE grade ≤1,
• Cockcroft-Gault-based creatinine clearance ≥50 mL/min. Note: Creatinine clearance (male) = (\[140-age in years\] × weight in kg)/ (\[serum creatinine in mg/dL\] × 72) Creatinine clearance (female) = (0.85 × \[140-age in years\] × weight in kg)/ (\[serum creatinine in mg/dL\] × 72),
• Serum albumin ≥3.0 g/dL (≥30 g/L),
• In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 × ULN. If the patient has liver metastases, ALT and AST ≤5 × ULN,
• Total serum bilirubin \<1.5 × ULN except for patients with Gilbert's syndrome who may be included if the total serum bilirubin is ≤3.0 × ULN or direct bilirubin ≤1.5 × ULN.

You may not qualify if:

• Active or newly diagnosed CNS metastases, including meningeal carcinomatosis.
• Breast cancer treatment-naïve patients in the metastatic setting.
• Prior therapy with elacestrant, onapristone, or chemotherapy in the metastatic setting.
• 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.
• Uncontrolled significant active infections.
• Patients with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection must have undetectable viral load during screening.
• Patients known to be HIV+ are allowed as long as they have undetectable viral load at baseline.
• Major surgery within 4 weeks before starting trial therapy.
• Inability to take oral medication, or history of malabsorption syndrome or any other uncontrolled gastrointestinal condition.
• Females of childbearing potential who:
• Within 28 days before study entry, did not use a highly effective method of contraception.
• Do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after trial therapy discontinuation.
• Males who do not agree to abstain from donating sperm, or to use a highly effective method of contraception, during the course of the treatment period and for 28 days thereafter.
• Known intolerance to either study drug or any of the excipients.
• Patient is currently receiving or received any of the following medications prior to first dose of trial therapy:

Sponsors & Collaborators

• Context Therapeutics Inc.: lead

Study Sites (3)

Cancer Treatment Centers of America - Western Regional Medical Center

Phoenix, Arizona, 85338, United States

Location

Cancer Treatment Centers of America - Midwestern Regional Center

Zion, Illinois, 60099, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

elacestrant; RAD1901; onapristone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2022
• First Posted: November 16, 2022
• Study Start: December 2, 2022
• Primary Completion: June 23, 2023
• Study Completion: June 23, 2023
• Last Updated: May 9, 2025

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)