RECRUITING

A Study of Enzalutamide, Enzalutamide in Combination With Mifepristone, or Chemotherapy in People With Metastatic Breast Cancer

Conditions

Metastatic Breast Cancer Enzalutamide Mifepristone Carboplatin Paclitaxel Capecitabine Eribulin Triple-negative Androgen receptor positive 22-334

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The researchers are doing this study to find out if the study drug, enzalutamide, alone or combined with the study drug, mifepristone, is effective in treating advanced or metastatic androgen receptor-positive (AR+) triple negative breast cancer (TNBC) or estrogen receptor-low breast cancer (ER-low BC), and whether these study treatments work as well as standard chemotherapy with carboplatin, paclitaxel, capecitabine, or eribulin.

Official Title

A RANDOMIZED, PHASE II STUDY OF ENZALUTAMIDE, ENZALUTAMIDE WITH MIFEPRISTONE, and TREATMENT OF PHYSICIAN'S CHOICE IN PATIENTS WITH AR+ METASTATIC TRIPLE-NEGATIVE OR ER-LOW BREAST CANCER

Quick Facts

Study Start:2023-10-18

Study Completion:2027-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06099769

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Female or male * Pathologically confirmed invasive breast cancer that is unresectable, locally advanced, or metastatic * TNBC (ER/PgR \<1%) or ER-low defined as: * ER and PgR 1-10% * HER2 negative per American Society of Clinical Oncology/College of American Pathologists guidelines * Local testing for ER/PgR and HER2 is acceptable for eligibility. * Tumor must be AR positive. AR is considered positive by IHC if ≥10% of cell nuclei are immunoreactive. * Evaluable or measurable disease per RECIST version 1.1; subjects with no evaluable AND no measurable disease (e.g., malignant effusions or bone marrow as the only manifestations of disease) are not eligible for enrollment. * Eligible for one of the chemotherapy options listed as TPC (eribulin, capecitabine, paclitaxel, or carboplatin), as per investigator assessment. * A representative, formalin-fixed, paraffin-embedded tumor specimen that enables the diagnosis of breast cancer, with adequate viable tumor cells in a tissue block (preferred) or 15 freshly cut unstained slides and 1 H\&E slide. Tissue from a metastatic site is preferred. * Patients may have received up to 2 prior lines of chemotherapy for metastatic breast cancer. * Patients with ER-low breast cancer may receive any number of lines of endocrine therapy +/- targeted therapy (i.e., CDK4/6 inhibitors, PI3K inhibitors). * Patients with PD-L1 positive breast cancer (CPS ≥ 10) should have received prior treatment with pembrolizumab in combination with chemotherapy in the first line setting unless there is a contraindication to checkpoint inhibitor therapy. * Patients may receive bisphosphonate or denosumab. * ECOG performance status 0-2. * Age ≥18 years. * Able to understand and the willingness to provide informed consent. * Patients must not have another active malignancy that requires treatment. * Women of child-bearing potential and men must agree to use 2 forms of adequate contraception (i.e., barrier contraception, abstinence, intrauterine device, or sterilization method) during study period and for 7 months following treatment end. Women must not breast feed while on study and for at least 3 months after final drug administration. * Ability to swallow intact enzalutamide and mifepristone. * Patient must be recovered from any recent major surgery. Radiation must have completed 14 days prior to study start. If treated in the second-line setting, the last chemotherapy or investigational anticancer therapy dose must be at least 14 days prior. * Adequate organ and marrow function, as defined below: * ANC ≥1000, hemoglobin ≥9 g/dL, platelets ≥100,000 * Total bilirubin ≤1.5x upper limit of normal (ULN), except for patients with known Gilbert syndrome; AST/ALT ≤3x ULN (≤5x ULN if liver metastases); creatinine ≤ 1.5x ULN. * Cortisol within normal limits * Patients must agree to research biopsy at study entry until 40 patients randomized to Arm A and 40 patients randomized to Arm B and 20 patients randomized to Arm C have been biopsied. * Biopsy requirement may be waived in consultation with the study PI (Drs. Traina or Nanda) if not medically feasible.	* History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past. History of loss of consciousness or transient ischemic attack within 12 months. * History of brain metastases or leptomeningeal disease. * Prior antiandrogen therapy (AR antagonist or CYP17 inhibitors). * Other concurrent investigational anticancer agents. * Confirmed QT interval with Fridericia correction (QTcF) \> 480 msec. * Any severe concurrent disease, infection, or comorbid condition that renders the patient inappropriate for enrollment in the opinion of the investigator or that interferes with the patient's ability to participate in the study requirements. * Pregnant patients are not eligible for study. * Women with a history of unexplained vaginal bleeding or with endometrial hyperplasia with atypia or endometrial carcinoma are excluded from study. * An active gastrointestinal disorder affecting absorption (e.g., gastrectomy, uncontrolled celiac disease). * Use of concurrent or chronic daily corticosteroid use. Topical or inhaled corticosteroids are permitted. * Use of concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4. Patients may be switched to alternative medications for eligibility purposes. A list of CYP3A4 substrates, inducers, and/or inhibitors * Hypersensitivity reaction to the active pharmaceutical ingredient or any of the tablet components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene.

Inclusion Criteria

Exclusion Criteria

* Female or male
* Pathologically confirmed invasive breast cancer that is unresectable, locally advanced, or metastatic
* TNBC (ER/PgR \<1%) or ER-low defined as:
* ER and PgR 1-10%
* HER2 negative per American Society of Clinical Oncology/College of American Pathologists guidelines
* Local testing for ER/PgR and HER2 is acceptable for eligibility.
* Tumor must be AR positive. AR is considered positive by IHC if ≥10% of cell nuclei are immunoreactive.
* Evaluable or measurable disease per RECIST version 1.1; subjects with no evaluable AND no measurable disease (e.g., malignant effusions or bone marrow as the only manifestations of disease) are not eligible for enrollment.
* Eligible for one of the chemotherapy options listed as TPC (eribulin, capecitabine, paclitaxel, or carboplatin), as per investigator assessment.
* A representative, formalin-fixed, paraffin-embedded tumor specimen that enables the diagnosis of breast cancer, with adequate viable tumor cells in a tissue block (preferred) or 15 freshly cut unstained slides and 1 H\&E slide. Tissue from a metastatic site is preferred.
* Patients may have received up to 2 prior lines of chemotherapy for metastatic breast cancer.
* Patients with ER-low breast cancer may receive any number of lines of endocrine therapy +/- targeted therapy (i.e., CDK4/6 inhibitors, PI3K inhibitors).
* Patients with PD-L1 positive breast cancer (CPS ≥ 10) should have received prior treatment with pembrolizumab in combination with chemotherapy in the first line setting unless there is a contraindication to checkpoint inhibitor therapy.
* Patients may receive bisphosphonate or denosumab.
* ECOG performance status 0-2.
* Age ≥18 years.
* Able to understand and the willingness to provide informed consent.
* Patients must not have another active malignancy that requires treatment.
* Women of child-bearing potential and men must agree to use 2 forms of adequate contraception (i.e., barrier contraception, abstinence, intrauterine device, or sterilization method) during study period and for 7 months following treatment end. Women must not breast feed while on study and for at least 3 months after final drug administration.
* Ability to swallow intact enzalutamide and mifepristone.
* Patient must be recovered from any recent major surgery. Radiation must have completed 14 days prior to study start. If treated in the second-line setting, the last chemotherapy or investigational anticancer therapy dose must be at least 14 days prior.
* Adequate organ and marrow function, as defined below:
* ANC ≥1000, hemoglobin ≥9 g/dL, platelets ≥100,000
* Total bilirubin ≤1.5x upper limit of normal (ULN), except for patients with known Gilbert syndrome; AST/ALT ≤3x ULN (≤5x ULN if liver metastases); creatinine ≤ 1.5x ULN.
* Cortisol within normal limits
* Patients must agree to research biopsy at study entry until 40 patients randomized to Arm A and 40 patients randomized to Arm B and 20 patients randomized to Arm C have been biopsied.
* Biopsy requirement may be waived in consultation with the study PI (Drs. Traina or Nanda) if not medically feasible.

* History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past. History of loss of consciousness or transient ischemic attack within 12 months.
* History of brain metastases or leptomeningeal disease.
* Prior antiandrogen therapy (AR antagonist or CYP17 inhibitors).
* Other concurrent investigational anticancer agents.
* Confirmed QT interval with Fridericia correction (QTcF) \> 480 msec.
* Any severe concurrent disease, infection, or comorbid condition that renders the patient inappropriate for enrollment in the opinion of the investigator or that interferes with the patient's ability to participate in the study requirements.
* Pregnant patients are not eligible for study.
* Women with a history of unexplained vaginal bleeding or with endometrial hyperplasia with atypia or endometrial carcinoma are excluded from study.
* An active gastrointestinal disorder affecting absorption (e.g., gastrectomy, uncontrolled celiac disease).
* Use of concurrent or chronic daily corticosteroid use. Topical or inhaled corticosteroids are permitted.
* Use of concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4. Patients may be switched to alternative medications for eligibility purposes. A list of CYP3A4 substrates, inducers, and/or inhibitors
* Hypersensitivity reaction to the active pharmaceutical ingredient or any of the tablet components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene.

Contacts and Locations

Study Contact

Tiffany Traina, MD

CONTACT

646-888-4558

trainat@mskcc.org

Ayca Gucalp, MD

CONTACT

646-888-4536

Principal Investigator

Tiffany Traina, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

University of Alabama at Birmingham

Birmingham, Alabama, 35294

United States

University of California San Francisco (Data collection only)

San Francisco, California, 94143

United States

University of Chicago Medical Center

Chicago, Illinois, 60637

United States

Dana Farber Cancer Institute (Data Collection Only)

Boston, Massachusetts, 02115

United States

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604

United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553

United States

University of North Carolina

Chapel Hill, North Carolina, 27514

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Tiffany Traina, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-10-18

Study Completion Date2027-10

Study Record Updates

Study Start Date2023-10-18

Study Completion Date2027-10

Terms related to this study

Keywords Provided by Researchers

Enzalutamide
Mifepristone
Carboplatin
Paclitaxel
Capecitabine
Eribulin
Triple-negative
Androgen receptor positive
22-334

Additional Relevant MeSH Terms

Metastatic Breast Cancer