Testing the Use of Fulvestrant and Binimetinib Targeted Treatment for NF1 Mutation in Hormone Receptor-Positive Metastatic Breast Cancer (A ComboMATCH Treatment Trial)

Stopped early · Phase 2

Conditions studied: Anatomic Stage IV Breast Cancer AJCC v8, Metastatic HER2-Negative Breast Carcinoma, Metastatic Hormone Receptor-Positive Breast Carcinoma

In brief

This phase II ComboMATCH treatment trial compares the usual treatment alone (fulvestrant) to using binimetinib plus the usual treatment in patients with hormone receptor positive breast cancer that has spread from where it first started to other places in the body (metastatic) and has an NF1 genetic change. Fulvestrant is a hormonal therapy that binds to estrogen receptors in tumor cells, resulting in estrogen receptor destruction and decreased estrogen binding, which may inhibit the growth of estrogen-sensitive tumor cells. Binimetinib is a targeted therapy that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The addition of binimetinib to fulvestrant in breast cancers with an NF1 genetic change could increase the percentage of tumors that shrink as well as lengthen the time that the tumors remain stable (without progression) as compared to fulvestrant alone.

Key facts

Study ID

NCT05554354

Run by

National Cancer Institute (NCI)

People needed

1

Starts

2024-09-13

Expected to finish

2025-04-04

Last updated by the study team

2026-03-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-N2 based on the presence of an actionable mutation as defined in EAY191
• The patient must be enrolled on the ComboMATCH Master Registration Trial EAY191
• Note: Patients must fulfill all eligibility criteria outlined in the ComboMATCH Registration Trial EAY191 at the time of registration to EAY191-N2. This includes submission of next-generation sequencing (NGS) data from one of the National Cancer Institute (NCI) credentialed designated laboratories for all potential patients prior to treatment trial assignment. Copy number and allele frequency cutoff as per the Registration protocol
• Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or, if disease cannot be safely biopsied, have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH registration trial (EAY191)
• Please note the current actionable marker of interest (aMOI)/actionable alteration list for this treatment trial can be found on the Cancer Trial Support Unit (CTSU) ComboMATCH Registration protocol page
• Please note novel/Dynamic aMOI can be submitted for review per the process described in the ComboMATCH Registration protocol
• A COMBOMATCH TREATMENT TRIAL EAY191-N2 ELIGIBILITY CRITERIA:
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Histologically or cytologically confirmed invasive breast carcinoma
• Confirmed metastatic disease by either imaging or tissue diagnosis
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and one additional lesion that can be biopsied (primary, metastatic both allowed)
• Patients must have inactivating or inferred inactivating NF1 alterations detected in tumor as determined by the ComboMATCH screening assessment
• The tumor must have been determined to be estrogen receptor (ER) and/or progesterone receptor (PgR) positive assessed by current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for hormone receptor testing. Patients with >= 1% ER or PgR staining by immunohistochemistry (IHC) are considered positive
• The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines
• Prior use of CDK4/6 inhibitor(i) is required
• Prior use of fulvestrant regardless of duration is allowed and will determine treatment assignment
• Up to one line of chemotherapy in metastatic setting is allowed
• Absolute neutrophil count >= 1,500/mm\^3
• Platelet count >= 100,000/ mm\^3
• Hemoglobin level >= 10 g/dL
• Creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula
• Total bilirubin level =< institutional upper limit of normal
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be =< 5.0 x ULN

You may not qualify if…

• Concurrent anticancer therapy
• Active autoimmune disease requiring systemic treatment within the past 3 months, documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
• Active brain metastasis. Brain metastases that have been stable for at least 1 month after completion of treatment are not an exclusion criterion
• History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous, chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
• Patients will be excluded if they currently have the following risk factors for RVO that are documented prior to the enrollment:
• Known uncontrolled glaucoma with intra-ocular pressures >= 21 mmHg
• Known serum cholesterol >= grade 2.
• Known hypertriglyceridemia >= grade 2
• Known hyperglycemia (fasting) >= grade 2
• Patients with baseline QT corrected for heart rate (QTc) > 500 ms, either induced by medication or congenital long QT syndrome will be excluded due to known side effects of binimetinib
• Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropathy) >= grade 2
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• Other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results
• Pregnancy or lactation at the time of registration or intention to become pregnant during the study (Note: Pregnancy testing according to institutional standards for patients of childbearing potential)
• For binimetinib, highly effective contraception should be used for at least 30 days after the last dose, and patients should not breastfeed for 3 days after the last dose
• For fulvestrant, highly effective contraception should be used for 1 year after the last dose, and patients should not breastfeed for 1 year after the last dose
• Use of any investigational product within 30 days prior to study entry
• INELIGIBILITY CRITERIA FOR COHORT 1, TREATMENT REGIMEN 2 PATIENTS WHO MIGRATE TO COHORT 2
• PATIENTS WHO MIGRATE TO COHORT 2: Not a candidate for binimetinib in the opinion of the treating investigator

Where it is running

• Kingman Regional Medical Center — Kingman, Arizona, United States
• PCR Oncology — Arroyo Grande, California, United States
• Epic Care-Dublin — Dublin, California, United States
• Epic Care Partners in Cancer Care — Emeryville, California, United States
• Contra Costa Regional Medical Center — Martinez, California, United States
• Saint Joseph Hospital - Orange — Orange, California, United States
• Saint John's Cancer Institute — Santa Monica, California, United States
• Epic Care Cyberknife Center — Walnut Creek, California, United States
• UM Sylvester Comprehensive Cancer Center at Aventura — Aventura, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Coral Gables — Coral Gables, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Deerfield Beach — Deerfield Beach, Florida, United States
• Mayo Clinic in Florida — Jacksonville, Florida, United States
• University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Kendall — Miami, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Plantation — Plantation, Florida, United States
• Saint Alphonsus Cancer Care Center-Boise — Boise, Idaho, United States
• Saint Luke's Cancer Institute - Boise — Boise, Idaho, United States
• Saint Alphonsus Cancer Care Center-Caldwell — Caldwell, Idaho, United States
• Kootenai Health - Coeur d'Alene — Coeur d'Alene, Idaho, United States
• Saint Luke's Cancer Institute - Fruitland — Fruitland, Idaho, United States
• Saint Luke's Cancer Institute - Meridian — Meridian, Idaho, United States
• Saint Alphonsus Cancer Care Center-Nampa — Nampa, Idaho, United States
• Saint Luke's Cancer Institute - Nampa — Nampa, Idaho, United States
• Kootenai Clinic Cancer Services - Post Falls — Post Falls, Idaho, United States
• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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