AzTrials
AzTrials

Anatomic Stage IV Breast Cancer AJCC v8Phase 2NCT05554354

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

A Phase 2 study testing Binimetinib, Biopsy Procedure and Biospecimen Collection in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic HER2-Negative Breast Carcinoma, run by National Cancer Institute (NCI) at 196 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Binimetinib, Biopsy Procedure and Biospecimen Collection
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
196 sitesin 2 countries
Study dates
13 Sep 2024to 4 Apr 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • For patients who will be assigned to Cohort 2 (fulvestrant-resistant), a left ventricular ejection fraction (LVEF) assessment must be performed within 12 weeks prior to registration. The LVEF must be >= 50% regardless of the cardiac imaging facility's lower limit of normal. (LVEF assessment performed by echocardiogram is preferred; however, MUGA scan may be substituted based on institutional/situational preferences)
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
  • ELIGIBILITY CRITERIA FOR COHORT 1, TREATMENT REGIMEN 2 PATIENTS WHO MIGRATE TO COHORT 2: Cohort migration: Patients treated with control treatment fulvestrant who experience disease progression may be eligible to migrate to Cohort 2 and receive combination treatment with binimetinib and fulvestrant. Patients who choose to do so must meet laboratory values and performance status requirements below and should begin treatment within 28 days
  • PATIENTS WHO MIGRATE TO COHORT 2: Patient's willingness to migrate to Cohort 2 affirmed
  • PATIENTS WHO MIGRATE TO COHORT 2: The patient must have an ECOG performance status of 0-2
  • PATIENTS WHO MIGRATE TO COHORT 2: Absolute neutrophil count >= 1,500/mm^3
  • PATIENTS WHO MIGRATE TO COHORT 2: Platelet count >= 100,000/ mm^3
  • PATIENTS WHO MIGRATE TO COHORT 2: Hemoglobin level >= 10 g/dL
  • PATIENTS WHO MIGRATE TO COHORT 2: Total bilirubin level =< institutional upper limit of normal (ULN)
  • PATIENTS WHO MIGRATE TO COHORT 2: AST and ALT must be =< 5.0 x ULN
  • PATIENTS WHO MIGRATE TO COHORT 2: Creatinine clearance (CrCL) of ≥30 mL/min by the Cockcroft-Gault formula
  • PATIENTS WHO MIGRATE TO COHORT 2: A LVEF performed within the last 3 months must be >= 50% regardless of the cardiac imaging facility's lower limit of normal (LVEF assessment performed by echocardiogram is preferred; however, MUGA scan may be substituted based on institutional/situational preferences)
  • PATIENTS WHO MIGRATE TO COHORT 2: Pregnancy test according to institutional standards must be negative (for patients of childbearing potential only)

Who cannot join

  • 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
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  • 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

Trial locations and contacts

196 sites in 2 countries.

196 sites in 2 countries

United States192 sites

  • UPMC Altoona

    Altoona, Pennsylvania, 16601

  • Community Hospital of Anaconda

    Anaconda, Montana, 59711

  • UI Health Care Mission Cancer and Blood - Ankeny Clinic

    Ankeny, Iowa, 50023

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • PCR Oncology

    Arroyo Grande, California, 93420

  • Duluth Clinic Ashland

    Ashland, Wisconsin, 54806

  • UM Sylvester Comprehensive Cancer Center at Aventura

    Aventura, Florida, 33180

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Advocate Good Shepherd Hospital

    Barrington, Illinois, 60010

  • Strecker Cancer Center-Belpre

    Belpre, Ohio, 45714

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • Lafayette Family Cancer Center-EMMC

    Brewer, Maine, 04412

  • Trinity Health IHA Medical Group Hematology Oncology - Brighton

    Brighton, Michigan, 48114

  • Trinity Health Medical Center - Brighton

    Brighton, Michigan, 48114

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • Trinity Health IHA Medical Group Hematology Oncology - Canton

    Canton, Michigan, 48188

  • Trinity Health Medical Center - Canton

    Canton, Michigan, 48188

  • Aultman Health Foundation

    Canton, Ohio, 44710

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • Chelsea Hospital

    Chelsea, Michigan, 48118

  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

    Chelsea, Michigan, 48118

  • Northwestern University

    Chicago, Illinois, 60611

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612

  • Advocate Illinois Masonic Medical Center

    Chicago, Illinois, 60657

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Kootenai Health - Coeur d'Alene

    Coeur d'Alene, Idaho, 83814

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Mount Carmel East Hospital

    Columbus, Ohio, 43213

  • The Mark H Zangmeister Center

    Columbus, Ohio, 43219

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • AMG Crystal Lake - Oncology

    Crystal Lake, Illinois, 60014

  • Aurora Saint Luke's South Shore

    Cudahy, Wisconsin, 53110

  • UPMC Western Maryland

    Cumberland, Maryland, 21502

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Premier Blood and Cancer Center

    Dayton, Ohio, 45409

  • Dayton Physician LLC - Englewood

    Dayton, Ohio, 45415

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Corewell Health Dearborn Hospital

    Dearborn, Michigan, 48124

  • Essentia Health - Deer River Clinic

    Deer River, Minnesota, 56636

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • UI Health Care Mission Cancer and Blood - Des Moines Clinic

    Des Moines, Iowa, 50309

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • Epic Care-Dublin

    Dublin, California, 94568

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Swedish Cancer Institute-Edmonds

    Edmonds, Washington, 98026

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Advocate Sherman Hospital

    Elgin, Illinois, 60123

  • Epic Care Partners in Cancer Care

    Emeryville, California, 94608

  • UPMC Hillman Cancer Center Erie

    Erie, Pennsylvania, 16505

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Corewell Health Farmington Hills Hospital

    Farmington Hills, Michigan, 48336

  • Cancer Hematology Centers - Flint

    Flint, Michigan, 48503

  • Genesee Hematology Oncology PC

    Flint, Michigan, 48503

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Aurora Cancer Care-Grafton

    Grafton, Wisconsin, 53024

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311

  • UPMC Cancer Centers - Arnold Palmer Pavilion

    Greensburg, Pennsylvania, 15601

  • Miami Valley Cancer Care and Infusion

    Greenville, Ohio, 45331

  • Gulfport Memorial Hospital

    Gulfport, Mississippi, 39502

  • Advocate South Suburban Hospital

    Hazel Crest, Illinois, 60429

  • OptumCare Cancer Care at Seven Hills

    Henderson, Nevada, 89052

  • Essentia Health Hibbing Clinic

    Hibbing, Minnesota, 55746

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Swedish Cancer Institute-Issaquah

    Issaquah, Washington, 98029

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Logan Health Medical Center

    Kalispell, Montana, 59901

  • Aurora Cancer Care-Kenosha South

    Kenosha, Wisconsin, 53142

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Kingman Regional Medical Center

    Kingman, Arizona, 86401

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

  • Northwestern Medicine Lake Forest Hospital

    Lake Forest, Illinois, 60045

  • Fairfield Medical Center

    Lancaster, Ohio, 43130

  • University of Michigan Health - Sparrow Lansing

    Lansing, Michigan, 48912

  • OptumCare Cancer Care at Charleston

    Las Vegas, Nevada, 89102

  • OptumCare Cancer Care at Fort Apache

    Las Vegas, Nevada, 89148

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • AMG Libertyville - Oncology

    Libertyville, Illinois, 60048

  • Condell Memorial Hospital

    Libertyville, Illinois, 60048

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

  • Henry Ford Saint John Hospital - Macomb Medical

    Macomb, Michigan, 48044

  • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

    Madison, Wisconsin, 53718

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Saint John's Hospital - Healtheast

    Maplewood, Minnesota, 55109

  • Marietta Memorial Hospital

    Marietta, Ohio, 45750

  • Aurora Bay Area Medical Group-Marinette

    Marinette, Wisconsin, 54143

  • Contra Costa Regional Medical Center

    Martinez, California, 94553-3156

  • Memorial Hospital

    Marysville, Ohio, 43040

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion

    Mechanicsburg, Pennsylvania, 17050

  • Riddle Memorial Hospital

    Media, Pennsylvania, 19063

  • Saint Luke's Cancer Institute - Meridian

    Meridian, Idaho, 83642

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • UM Sylvester Comprehensive Cancer Center at Kendall

    Miami, Florida, 33176

  • Aurora Cancer Care-Milwaukee

    Milwaukee, Wisconsin, 53209

  • Aurora Saint Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Aurora Sinai Medical Center

    Milwaukee, Wisconsin, 53233

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Community Medical Center

    Missoula, Montana, 59804

  • UPMC Hillman Cancer Center - Monroeville

    Monroeville, Pennsylvania, 15146

  • Knox Community Hospital

    Mount Vernon, Ohio, 43050

  • Saint Alphonsus Cancer Care Center-Nampa

    Nampa, Idaho, 83687

  • Saint Luke's Cancer Institute - Nampa

    Nampa, Idaho, 83687

  • Licking Memorial Hospital

    Newark, Ohio, 43055

  • Providence Newberg Medical Center

    Newberg, Oregon, 97132

  • Advocate Christ Medical Center

    Oak Lawn, Illinois, 60453-2699

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Saint Alphonsus Cancer Care Center-Ontario

    Ontario, Oregon, 97914

  • Saint Joseph Hospital - Orange

    Orange, California, 92868

  • Providence Willamette Falls Medical Center

    Oregon City, Oregon, 97045

  • Northwestern Medicine Orland Park

    Orland Park, Illinois, 60462

  • Vince Lombardi Cancer Clinic - Oshkosh

    Oshkosh, Wisconsin, 54904

  • Paoli Memorial Hospital

    Paoli, Pennsylvania, 19301

  • Advocate Lutheran General Hospital

    Park Ridge, Illinois, 60068

  • Mercy Health - Perrysburg Hospital

    Perrysburg, Ohio, 43551

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • UPMC-Passavant Hospital

    Pittsburgh, Pennsylvania, 15237

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

  • Southern Ohio Medical Center

    Portsmouth, Ohio, 45662

  • Kootenai Clinic Cancer Services - Post Falls

    Post Falls, Idaho, 83854

  • Aurora Cancer Care-Racine

    Racine, Wisconsin, 53406

  • Valley Medical Center

    Renton, Washington, 98055

  • Virginia Cancer Institute

    Richmond, Virginia, 23229

  • VCU Massey Cancer Center at Stony Point

    Richmond, Virginia, 23235

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Corewell Health William Beaumont University Hospital

    Royal Oak, Michigan, 48073

  • MyMichigan Medical Center Saginaw

    Saginaw, Michigan, 48601

  • Oncology Hematology Associates of Saginaw Valley PC

    Saginaw, Michigan, 48604

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Kootenai Clinic Cancer Services - Sandpoint

    Sandpoint, Idaho, 83864

  • Essentia Health Sandstone

    Sandstone, Minnesota, 55072

  • Saint John's Cancer Institute

    Santa Monica, California, 90404

  • Vince Lombardi Cancer Clinic-Sheboygan

    Sheboygan, Wisconsin, 53081

  • Memorial Hospital East

    Shiloh, Illinois, 62269

  • Sanford Cancer Center Oncology Clinic

    Sioux Falls, South Dakota, 57104

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • VCU Community Memorial Health Center

    South Hill, Virginia, 23970

  • Springfield Regional Cancer Center

    Springfield, Ohio, 45504

  • Springfield Regional Medical Center

    Springfield, Ohio, 45504

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • Aurora Medical Center in Summit

    Summit, Wisconsin, 53066

  • MyMichigan Medical Center Tawas

    Tawas City, Michigan, 48764

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • Mercy Health - Saint Anne Hospital

    Toledo, Ohio, 43623

  • Corewell Health Beaumont Troy Hospital

    Troy, Michigan, 48085

  • Upper Valley Medical Center

    Troy, Ohio, 45373

  • Saint Luke's Cancer Institute - Twin Falls

    Twin Falls, Idaho, 83301

  • Vince Lombardi Cancer Clinic-Two Rivers

    Two Rivers, Wisconsin, 54241

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • Essentia Health Virginia Clinic

    Virginia, Minnesota, 55792

  • Epic Care Cyberknife Center

    Walnut Creek, California, 94597

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

  • Aurora Cancer Care-Milwaukee West

    Wauwatosa, Wisconsin, 53226

  • Aurora West Allis Medical Center

    West Allis, Wisconsin, 53227

  • Saint Mary's Oncology/Hematology Associates of West Branch

    West Branch, Michigan, 48661

  • Saint Ann's Hospital

    Westerville, Ohio, 43081

  • Asplundh Cancer Pavilion

    Willow Grove, Pennsylvania, 19090

  • Lankenau Medical Center

    Wynnewood, Pennsylvania, 19096

  • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

    Yakima, Washington, 98902

  • Huron Gastroenterology PC

    Ypsilanti, Michigan, 48106

  • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

    Ypsilanti, Michigan, 48197

  • Genesis Healthcare System Cancer Care Center

    Zanesville, Ohio, 43701

Other trials in United States

Puerto Rico4 sites

  • Puerto Rico Hematology Oncology Group

    Bayamón, 00961

  • Doctors Cancer Center

    Manati, 00674

  • Centro Comprensivo de Cancer de UPR

    San Juan, 00927

  • PROncology

    San Juan, 00927

Other trials in Puerto Rico

About this study

Official title: Phase 2 Trial of Fulvestrant and Binimetinib in Patients With Hormone Receptor-Positive Metastatic Breast Cancer With Inactivating or Inferred Inactivating NF1 Alterations: A ComboMATCH Treatment Trial

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine whether the combination of fulvestrant and binimetinib improves progression-free survival (PFS) compared to treatment with fulvestrant alone in patients not previously treated with fulvestrant. (Cohort 1) II. To determine whether overall response rate (ORR) within 4 months in patients who have previously progressed on a fulvestrant-containing regimen is greater than 10%, as a historical comparison, when these patients receive combination fulvestrant and binimetinib therapy. (Cohort 2)

SECONDARY OBJECTIVES:

  1. To estimate ORR at any time after the start of the treatment for Cohort 2 and separately for the two arms in Cohort 1.

II. To estimate PFS distribution in Cohort 2. III. To estimate clinical benefit rate separately for the two arms in Cohort 1 and Cohort 2.

IV. To determine the safety and toxicity profile in both cohorts. V. To estimate the overall survival (OS) in both cohorts. VI. Collect tissue and provide it to the ComboMATCH Registration Protocol to assess concordance between the diagnostic tumor mutation profile generated by the Designated Laboratories, the pre-treatment biopsy mutation profile, and the pre-treatment circulating tumor deoxyribonucleic acid (DNA) (ctDNA) mutation profile from plasma, as described in ComboMATCH Registration Protocol. For this treatment substudy, the outcome objective will be to report the proportion of cases providing sufficient tissue for that integrated scientific activity in the ComboMATCH Registration Protocol.

EXPLORATORY BIOMARKER OBJECTIVES:

  1. To analyze the cell-free (cf)DNA at progression to determine the changes in cfDNA profile in order to understand blood-based mutation dynamics.

II. To analyze RNAseq at progression to determine potential pathways that are altered that may contribute to the sensitivity/resistance.

III. To discover/detect novel biomarkers using microscaled proteogenomics by analyzing the proteins and phosphor-proteins along with genomics to determine potential pathways that may correlate with the response to the combination treatment.

IV. To detect the loss of NF1, using immunohistochemistry staining to precisely measure the level of the NF1 protein.

  1. To determine the variant allele frequency (VAF) of mutant NF1 measuring by using droplet digital polymerase chain reaction (ddPCR) for the targeted NF1 gene level.

OUTLINE: Patients who are fulvestrant naive are assigned to Cohort I, while patients who are fulvestrant resistant are assigned to Cohort II.

COHORT I: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive fulvestrant intramuscularly (IM) on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles and binimetinib orally (PO) twice daily (BID) on days 15 to 28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a computed tomography (CT), magnetic resonance imaging (MRI), or bone scan, echocardiography (ECHO) or multi-gated acqusition scan (MUGA), and tumor biopsy, as well as possible blood sample collection during screening and on study.

ARM II: Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress on fulvestrant alone may migrate to cohort II if they meet the migration eligibility criteria. Patients not willing to migrate to cohort II will have further therapy at the investigator's discretion. Patients undergo a CT, MRI, or bone scan and tumor biopsy, as well as ECHO or MUGA and possible blood sample collection during screening and on study.

COHORT II: Patients receive fulvestrant IM on day 1 of each cycle and binimetinib PO BID on days 15-28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, MRI, or bone scan, ECHO or MUGA and tumor biopsy, as well as possible blood sample collection during screening and on study.

Upon completion of study treatment patients are followed up every 6 months for 5 years.

Being tested
Binimetinib, Biopsy Procedure, Biospecimen Collection, Bone Scan, Computed Tomography

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BinimetinibDrug

    Also called ARRY 162, ARRY 438162, ARRY-162, ARRY-438162

    Given PO

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo tumor biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone ScanProcedure or surgery

    Also called Bone Scintigraphy

    Undergo bone scan

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • FulvestrantDrug

    Also called Faslodex, Faslodex(ICI 182,780), ICI 182,780, ICI 182780

    Given IM

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

Study groups in NCT05554354
Study groupRoleWhat they receive
Cohort I (Arm I) (fulvestrant, binimetinib)ExperimentalPatients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles and binimetinib PO BID on days 15 to 28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT, MRI, or bone scan, ECHO or MUGA, and tumor biopsy, as well as possible blood sample collection during screening and on study.
Receives: Drug: Binimetinib; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Echocardiography Test; Drug: Fulvestrant; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan
Cohort I (Arm II)Active comparatorPatients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress on fulvestrant alone may migrate to cohort II if they meet the migration eligibility criteria. Patients not willing to migrate to cohort II will have further therapy at the investigator's discretion. Patients undergo a CT, MRI, or bone scan and tumor biopsy, as well as ECHO or MUGA and possible blood sample collection during screening and on study.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Echocardiography Test; Drug: Fulvestrant; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan
Cohort II (fulvestrant, binimetinib)ExperimentalPatients receive fulvestrant IM on day 1 of each cycle and binimetinib PO BID on days 15-28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, MRI, or bone scan, ECHO or MUGA and tumor biopsy, as well as possible blood sample collection during screening and on study.
Receives: Drug: Binimetinib; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Echocardiography Test; Drug: Fulvestrant; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS) (Cohort I)

    PFS of the two study arms will be compared by log-rank test (1-sided, alpha=0.1). Kaplan-Meier plot will be provided. Hazard ratio (HR) and the corresponding 95% confidence interval (CI) will be estimated by Cox proportional model using treatment as covariate.

    Measured: The duration between randomization and progression or death from all cause, whichever happens first, assessed up to 5 years

  2. Objective Response Rate (ORR) (Cohort II)

    ORR is the percentage of patients who reaches a complete or partial response (defined by Response Evaluation Criteria in Solid Tumors [RECIST] version[v]1.1) within 4 months of the start of the treatment. ORR will be calculated as the proportion of patients achieved partial response (PR) or complete response (CR) within 4 months after the initiation of the treatment. ORR will be reported with corresponding 95% exact CI. Patients who have withdrawn from the study before any efficacy follow up are considered non-evaluable for clinical response and will be replaced.

    Measured: Within 4 months of the start of treatment

Secondary outcomes (6)

  1. ORR for Each Study Arm (Cohort I)

    ORR is the percentage of patients who reach a complete or partial response (defined by RECIST v1.1) any time after the start of the treatment. ORR for each study arm will be calculated with corresponding 95% exact CI. Fisher exact test will be used to compare the ORR of the two study arms.

    Measured: Any time after the start of the treatment, assessed up to 5 years

  2. ORR (Cohort II)

    ORR is the percentage of patients who reach a complete or partial response (defined by RECIST v1.1) any time after the start of the treatment.

    Measured: Any time after the start of the treatment, assessed up to 5 years

  3. Clinical Benefit Rate

    Defined as proportion of patients who achieved a CR, PR, or stable disease defined by RECIST criteria any time after the start of the treatment. Clinical benefit rate will be analyzed for each arm of cohort I and cohort II as described for ORR. ORR for each study arm will be calculated with corresponding 95% exact CI. Fisher exact test will be used to compare the ORR of the two study arms.

    Measured: Any time after the start of the treatment, assessed up to 5 years

  4. PFS (Cohort II)

    PFS for cohort II will be summarized using the Kaplan-Meier's method. Median PFS with corresponding 95% CI will be provided.

    Measured: The duration between randomization and progression or death from all cause, whichever happens first, assessed up to 5 years

  5. Overall Survival (OS)

    OS for cohort I will be analyzed as described for PFS in cohort I and OS for cohort II will be analyzed as described for PFS in cohort II. PFS of the two study arms will be compared by log-rank test (1-sided, alpha=0.1). Kaplan-Meir plot will be provided. HR and the corresponding 95% CI will be estimated by Cox proportional model using treatment as covariate. PFS for Cohort 2 will be summarized using the Kaplan-Meir's method. Median PFS with corresponding 95% CI will be provided.

    Measured: The duration between randomization and death of all causes, assessed up to 5 years

  6. Incidence of Adverse Events

    The grade of toxicity measurement will follow Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The distribution by treatment group of the highest grade of each CTCAEs experienced by each patient categorized will be tabulated. The tabulations will also be reviewed on a semi-annual basis by the Data Monitoring Committee. These tabulations will include summaries by system organ class and summaries by term under each system organ class.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2022
  2. Study start13 Sep 2024
  3. Primary completion4 Apr 2025
  4. Study completion4 Apr 2025

Why it stopped: Other - slow accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05554354
Sponsor's protocol ID
NCI-2022-07265
Other IDs
NCI-2022-07265, EAY191-N2, EAY191-N2, U10CA180868
Status last verified
Aug 2025
First submitted
22 Sep 2022
Last updated
3 Mar 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Binimetinib, Biopsy Procedure and Biospecimen Collection in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic HER2-Negative Breast Carcinoma, run by National Cancer Institute (NCI) at 196 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 39 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 196 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (Cohort I) (time frame: The duration between randomization and progression or death from all cause, whichever happens first, assessed up to 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05554354.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2026.

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