Trial Title:
A Study of Enzalutamide, Enzalutamide in Combination with Mifepristone, or Chemotherapy in People with Metastatic Breast Cancer
NCT ID:
NCT06099769
Condition:
Metastatic Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Mifepristone
Conditions: Keywords:
Enzalutamide
Mifepristone
Carboplatin
Paclitaxel
Capecitabine
Eribulin
Triple-negative
Androgen receptor positive
22-334
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Crossover Assignment
Intervention model description:
This phase II study will randomize.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Enzalutamide
Description:
mouth once daily (160 mg/day)
Arm group label:
Enzalutamide
Arm group label:
Enzalutamide with Mifepristone
Intervention type:
Drug
Intervention name:
Mifepristone
Description:
mouth once daily 300-mg tablet
Arm group label:
Enzalutamide with Mifepristone
Intervention type:
Drug
Intervention name:
TPC
Description:
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 group label:
Chemotherapy:Carboplatin, Paclitaxel, Eribulin or Capecitabine (TPC)
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.
Criteria for eligibility:
Criteria:
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 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.
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Alabama at Birmingham
Address:
City:
Birmingham
Zip:
35294
Country:
United States
Status:
Recruiting
Contact:
Last name:
Katia Khoury, MD
Phone:
205-801-9034
Facility:
Name:
University of California San Francisco (Data collection only)
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hope Rugo, MD
Phone:
415 353-7070
Facility:
Name:
University of Chicago Medical Center
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rita Nanda, MD
Phone:
773-834-2756
Facility:
Name:
Dana Farber Cancer Institute (Data Collection Only)
Address:
City:
Boston
Zip:
02115
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Erica Mayer, MD, MPH
Phone:
617-632-3800
Facility:
Name:
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tiffany Traina, MD
Phone:
646-888-4558
Facility:
Name:
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tiffany Traina, MD
Phone:
646-888-4558
Facility:
Name:
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tiffany Traina, MD
Phone:
646-888-4558
Facility:
Name:
Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tiffany Traina, MD
Phone:
646-888-4558
Facility:
Name:
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tiffany Traina, MD
Phone:
646-888-4558
Contact backup:
Last name:
Ayca Gucalp, MD
Phone:
646-888-4536
Contact backup:
Last name:
Tiffany Traina, MD
Facility:
Name:
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Address:
City:
Uniondale
Zip:
11553
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tiffany Traina, MD
Phone:
646-888-4558
Facility:
Name:
Memorial Sloan Kettering Westchester (All Protocol Activities)
Address:
City:
West Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tiffany Traina, MD
Phone:
646-888-4558
Facility:
Name:
University of North Carolina
Address:
City:
Chapel Hill
Zip:
27514
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Lisa Carey, MD
Phone:
919-843-6814
Start date:
October 18, 2023
Completion date:
October 2027
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Collaborator:
Agency:
Astellas Pharma US, Inc.
Agency class:
Industry
Collaborator:
Agency:
Breast Cancer Research Foundation
Agency class:
Other
Collaborator:
Agency:
Corcept Therapeutics
Agency class:
Industry
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06099769
http://www.mskcc.org/mskcc/html/44.cfm
