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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT06099769

Collaborator

Astellas Pharma US, Inc. (Industry), Breast Cancer Research Foundation (Other), Corcept Therapeutics (Industry)

201

Enrollment

Locations

Arms

47.4

Anticipated Duration (Months)

33.5

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Enzalutamide Drug: Mifepristone Drug: TPC	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

201 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

This phase II study will randomize.This phase II study will randomize.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 18, 2023

Anticipated Primary Completion Date :

Oct 1, 2027

Anticipated Study Completion Date :

Oct 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Enzalutamide Enzalutamide 160 mg/day, continuous daily dosing in a 21-day cycle	Drug: Enzalutamide mouth once daily (160 mg/day)
Experimental: Enzalutamide with Mifepristone Enzalutamide 120mg/day and mifepristone 300mg/day, continuous daily dosing in a 21-day cycle	Drug: Enzalutamide mouth once daily (160 mg/day) Drug: Mifepristone mouth once daily 300-mg tablet
Active Comparator: Chemotherapy:Carboplatin, Paclitaxel, Eribulin or Capecitabine (TPC) The treating physician must select from one of the following regimens. Eribulin 1.4 mg/m2 IV Day 1 and Day 8 in a 21-day cycle Capecitabine 1000-1250 mg/m2 twice daily, orally Day 1-14 in a 21-day cycle Paclitaxel 80 mg/m2 IV Day 1, Day 8 in a 21-day cycle Carboplatin AUC 6 IV Day 1 in a 21-day cycle Carboplatin AUC 2 IV Day 1, Day 8 and Day 15 in a 21-day cycle Patients randomized to TPC may be offered crossover to enzalutamide plus mifepristone treatment at the time of disease progression if they continue to meet eligibility criteria.	Drug: TPC The treating physician must select from one of the following regimens: Eribulin 1.4 mg/m2 IV Day 1 and Day 8 in a 21-day cycle Capecitabine 1000-1250 mg/m2 twice daily, orally Day 1-14 in a 21-day cycle Paclitaxel 80 mg/m2 IV Day 1, Day 8 in a 21-day cycle Carboplatin AUC 6 IV Day 1 in a 21-day cycle Carboplatin AUC 2 IV Day 1, Day 8 and Day 15 in a 21-day cycle

Arm

Intervention/Treatment

Experimental: Enzalutamide

Enzalutamide 160 mg/day, continuous daily dosing in a 21-day cycle

Drug: Enzalutamide

mouth once daily (160 mg/day)

Experimental: Enzalutamide with Mifepristone

Enzalutamide 120mg/day and mifepristone 300mg/day, continuous daily dosing in a 21-day cycle

Drug: Enzalutamide

mouth once daily (160 mg/day)

Drug: Mifepristone

mouth once daily 300-mg tablet

Active Comparator: Chemotherapy:Carboplatin, Paclitaxel, Eribulin or Capecitabine (TPC)

The treating physician must select from one of the following regimens. Eribulin 1.4 mg/m2 IV Day 1 and Day 8 in a 21-day cycle Capecitabine 1000-1250 mg/m2 twice daily, orally Day 1-14 in a 21-day cycle Paclitaxel 80 mg/m2 IV Day 1, Day 8 in a 21-day cycle Carboplatin AUC 6 IV Day 1 in a 21-day cycle Carboplatin AUC 2 IV Day 1, Day 8 and Day 15 in a 21-day cycle Patients randomized to TPC may be offered crossover to enzalutamide plus mifepristone treatment at the time of disease progression if they continue to meet eligibility criteria.

Drug: TPC

The treating physician must select from one of the following regimens: Eribulin 1.4 mg/m2 IV Day 1 and Day 8 in a 21-day cycle Capecitabine 1000-1250 mg/m2 twice daily, orally Day 1-14 in a 21-day cycle Paclitaxel 80 mg/m2 IV Day 1, Day 8 in a 21-day cycle Carboplatin AUC 6 IV Day 1 in a 21-day cycle Carboplatin AUC 2 IV Day 1, Day 8 and Day 15 in a 21-day cycle

Outcome Measures

Primary Outcome Measures

progression-free survival (PFS) [2 years]
Response and progression will be evaluated in this study using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) Committee (version 1.1).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion 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.

°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 1 prior line 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.

Exclusion Criteria:

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

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	University of California San Francisco (Data collection only)	San Francisco	California	United States	94143
3	University of Chicago Medical Center	Chicago	Illinois	United States	60637
4	Dana Farber Cancer Institute (Data Collection Only)	Boston	Massachusetts	United States	02115
5	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
6	University of North Carolina	Chapel Hill	North Carolina	United States	27514