A Study of Enzalutamide, Enzalutamide in Combination With Mifepristone, or Chemotherapy in People With Metastatic Breast Cancer
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
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests enzalutamide alone or with mifepristone to see if they work as well as standard chemotherapy. It is for adults with advanced breast cancer that cannot be removed by surgery or has spread. The cancer must be triple-negative or have low estrogen receptors, and must have androgen receptors—proteins that respond to certain hormones.
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.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Be age 18 or older, of any sex, and able to understand and agree to join the study.
- Have confirmed triple-negative or low-estrogen-receptor breast cancer that is HER2-negative. At least 10% of tumor cells must test positive for androgen receptors.
- Have cancer that can be checked or measured, and be able to receive one of the study’s chemotherapy options.
- Have had no more than 2 rounds of different chemotherapy treatments for breast cancer that has spread. If your cancer is PD-L1 positive, you should have had immune therapy unless it was unsafe for you.
- Be able to care for yourself and be out of bed or a chair for at least half the day. Have blood counts, liver and kidney tests, and cortisol hormone levels that meet study rules.
- Provide a tumor sample. Agree to a research biopsy, if still required; this may be waived if it is not medically safe.
- Be able to swallow the study pills whole and have recovered from major surgery. Finish radiation at least 14 days before starting; a 14-day wait after prior cancer drugs also applies in some cases.
- If able to have children, agree to use 2 forms of birth control during treatment and for 7 months after. Do not breastfeed during treatment or for at least 3 months after the last dose.
Who can't join
- A history of seizures or conditions that raise seizure risk; fainting or a mini-stroke in the past 12 months.
- Any history of cancer spreading to the brain or the tissues around the brain and spinal cord.
- Past treatment with drugs that block androgen hormones, or current use of other experimental cancer drugs.
- Another active cancer needing treatment, a serious illness or infection, or a heart rhythm test showing a QTcF above 480 milliseconds.
- Pregnancy, unexplained vaginal bleeding, cancer of the womb lining, or abnormal precancerous growth of that lining.
- A digestive problem that affects how your body absorbs medicine.
- Current or long-term daily steroid use, except skin creams or inhalers. Certain medicines that affect how the body processes drugs are also not allowed, but switching medicines may be possible.
- An allergy to the study drugs or any ingredients in their tablets.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: Screening Cohort (non-MSK patients only): * Age ≥18 years at time of consent * signed the pre-screening informed consent document to allow for AR testing as part of study screening Treatment Cohort: * 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. °AR testing performed locally must use protocol specified methodology to be acceptable for eligibility. Central testing is an option for those unable to perform local testing per this methodology. Please refer to the Section entitled "Treatment Plan" for AR testing methodology or refer to the laboratory manual. * 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. If not available, tissue from the primary site may be obtained. * 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 a checkpoint inhibitor 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. Exclusion Criteria: * Seizure disorder 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.
Study sites (12)
AL
- University of Alabama at Birmingham · Birmingham, AL 35294Katia Khoury, MD · Study contact · 205-801-9034More trials in Birmingham
CA
- University of California San Francisco (Data collection only) · San Francisco, CA 94143Hope Rugo, MD · Study contact · 415-353-7070More trials in San Francisco
IL
- University of Chicago Medical Center · Chicago, IL 60637Rita Nanda, MD · Study contact · 773-834-2756More trials in Chicago
MA
- Dana Farber Cancer Institute (Data Collection Only) · Boston, MA 02115Erica Mayer, MD, MPH · Study contact · 617-632-3800More trials in Boston
NC
- University of North Carolina · Chapel Hill, NC 27514Lisa Carey, MD · Study contact · 919-843-6814More trials in Chapel Hill
NJ
- Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) · Basking Ridge, NJ 07920Tiffany Traina, MD · Study contact · 646-888-4558More trials in Basking Ridge
- Memorial Sloan Kettering Monmouth (Limited Protocol Activities) · Middletown, NJ 07748Tiffany Traina, MD · Study contact · 646-888-4558More trials in Middletown
- Memorial Sloan Kettering Bergen (Limited Protocol Activities) · Montvale, NJ 07645Tiffany Traina, MD · Study contact · 646-888-4558More trials in Montvale
NY
- Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities) · Commack, NY 11725Tiffany Traina, MD · Study contact · 646-888-4558More trials in Commack
- Memorial Sloan Kettering Westchester (All Protocol Activities) · Harrison, NY 10604Tiffany Traina, MD · Study contact · 646-888-4558More trials in Harrison
- Memorial Sloan Kettering Cancer Center (All Protocol Activities) · New York, NY 10065Tiffany Traina, MD · Study contact · 646-888-4558Ayca Gucalp, MD · Study contact · 646-888-4536Tiffany Traina, MD · Principal investigatorMore trials in New York
- Memorial Sloan Kettering Nassau (Limited Protocol Activities) · Uniondale, NY 11553Tiffany Traina, MD · Study contact · 646-888-4558More trials in Uniondale