AzTrials
AzTrials

Advanced Biliary Tract CarcinomaPhase 2NCT05564403

Study of Chemotherapy, With or Without Binimetinib in Advanced Biliary Tract Cancers in 2nd Line Setting (A ComboMATCH Treatment Trial)

A Phase 2 study testing Binimetinib, Biopsy Procedure and Biospecimen Collection in people with Advanced Biliary Tract Carcinoma and Advanced Gallbladder Carcinoma, run by National Cancer Institute (NCI) at 207 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

This phase II ComboMATCH treatment trial compares the usual treatment of modified leucovorin, fluorouracil and oxaliplatin (mFOLFOX6) chemotherapy to using binimetinib plus mFOLFOX6 chemotherapy to shrink tumors in patients with biliary tract cancers that have spread to other places in the body (advanced) and had… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Binimetinib, Biopsy Procedure and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
207 sitesUnited States
Study dates
9 Feb 2024to 15 Oct 2027
Phase
Phase 2

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-A6 based on the presence of an actionable mutation as defined in EAY191
  • GENERAL COMBOMATCH EAY191:
  • Patients must be registered to the ComboMATCH Registration Protocol (EAY191)
  • Patients must have RAS/RAF/MEK/ERK mutations as determined by the ComboMATCH screening assessment
  • Patients must not have BRAF V600E as determined by the ComboMATCH screening assessment
  • Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have archival tissue available from within 12 months prior to registration on the ComboMATCH Registration Trial (EAY191).
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  • Please note the current actionable marker of interest (aMOI)/actionable alteration list for this treatment trial can be found on the Cancer Trials Support Unit (CTSU) website
  • Please note novel/Dynamic aMOI can be submitted for review per the process described in the ComboMATCH Registration Protocol
  • EAY191-A6 REGISTRATION:
  • Participants must have histologically confirmed BTC (intrahepatic cholangiocarcinoma [IHC], extrahepatic cholangiocarcinoma [EHC] or gallbladder cancer [GBC]) that is unresectable or recurrent with a confirmed RAS/RAF/MEK/ERK pathway mutation via any Clinical Laboratory Improvement Act (CLIA)-certified method. BRAFV600E mutations are not eligible due to other ongoing/upcoming studies in this disease cohort
  • Tumor tissue must be available:
  • Adequate archival tumor specimen (obtained within 12 months of EAY191 registration which has not had a Response Evaluation Criteria in Solid Tumors (RECIST) response, complete response (CR) or partial response (PR), to any intervening therapy after collection of the tissue) must be available with formalin-fixed paraffin-embedded tumor tissue (blocks or slides) OR
  • Consent to a new tumor tissue biopsy which is not a representative target lesion. This lesion must be amenable to a minimal risk image-guided or direct vision biopsy
  • A new biopsy is preferred but is not required for enrollment in EAY191-A6 if sufficient archival tissue is available as described above.
  • Measurable disease per RECIST 1.1 Of note, in the case when a baseline biopsy is done after scans are obtained, a lesion separate from one that is biopsied needs to be measurable per RECIST 1.1. All radiologic studies must be performed within 28 days prior to registration
  • Progression of disease on gemcitabine based first-line regimen (i.e. only one prior line of therapy is permitted)
  • No systemic anti-cancer therapy within 4 weeks of registration to EAY191-A6
  • No prior MEK inhibitor therapy
  • No prior history of treatment with a direct and specific inhibitor of KRAS
  • Patients who only received radio-sensitizing chemotherapy with fluorouracil (5-FU) or capecitabine are eligible, but need to have received and failed first-line systemic chemotherapy upon recurrence. Peri-operative systemic 5-FU/capecitabine and/or oxaliplatin, is allowed if it's been more than 12 months of registration to EAY191-A6
  • No major surgery within 4 weeks (excluding placement of vascular access) of registration to EAY191-A6
  • No minor surgery within 2 weeks of registration to EAY191-A6
  • No palliative radiotherapy within 1 week of registration to EAY191-A6
  • Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
  • Therefore, for women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
  • Adequate contraception is needed for at least 30 days after the last dose of binimetinib and breastfeeding should be discontinued for at least 3 days after the last dose of binimetinib. For FOLFOX regimen, 9 months is recommended for contraception after last dose of oxaliplatin for females of childbearing potential and 6 months for males
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Absolute neutrophil count (ANC) >= 1,000/mm^3, no growth factor within 14 days of 1st dose
  • Platelet count >= 75,000/mm^3
  • Creatinine < 1.6 x upper limit of normal (ULN) OR
  • Calculated (Calc.) creatinine clearance >= 50 mL/min, as calculated by the Cockcroft-Gault formula
  • Total bilirubin =< 2.0 x upper limit of normal (ULN); Patients with Gilbert syndrome may enroll if < 3.0 x ULN
  • Aspartate aminotransferase (AST) /alanine aminotransferase (ALT) =< 5.0 x upper limit of normal (ULN)
  • Hemoglobin >= 8 g/dL, no transfusion within 7 days of 1st dose
  • Creatine phosphokinase =< 2.5 x ULN
  • High blood pressure more than 160/90 despite treatment are ineligible
  • No history of interstitial lung disease. No history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Patients should not have history of bowel perforation or intestinal fistulas in the last 6 months
  • Patients with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease are ineligible
  • Must have adequate cardiac function with left ventricular ejection fraction >= 50% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan. Patients with congenital long QT syndrome are not permitted
  • No history of prolonged QTc or at risk for prolonged QTc due to any reason (for example, concomitant medications during or before chemotherapy that may increase the risk of prolonged QTc), uncontrolled congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]), myocardial infarction within the last 6 months, unstable arrhythmias, unstable angina or severe obstructive pulmonary disease
  • No active skin disorder that has required systemic therapy within the past 1 year
  • No history of rhabdomyolysis
  • No concurrent ocular disorders, including:
  • Patients with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including but not limited to uncontrolled hypertension, uncontrolled diabetes
  • Patients with history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, intraocular pressure > 21 mm Hg as measured by tonometry, or other significant ocular pathology, such as anatomical abnormalities that increase the risk for RVO
  • Patients with a history of corneal erosion (instability of corneal epithelium), corneal degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions
  • Patients with known or at risk for retinopathies, uveitis or retinal vein occlusion
  • No patients with a history of hypersensitivity to any of the inactive ingredients in binimetinib, nor known severe allergic reactions or hypersensitivity of 5-FU, leucovorin (LV) or oxaliplatin will be allowed to participate in this study for safety concerns
  • No other medical condition (e.g. cardiac, gastrointestinal, pulmonary, psychiatric, neurological, genetic, etc.) that in the opinion of the investigator would places the subject at unacceptably high risk for toxicity
  • No prior allogeneic stem cell or solid organ transplantation
  • Central nervous system (CNS) metastases must have been treated with local therapy (surgery, radiation, ablation) with systemic steroids tapered to a physiologic dose (10 mg or prednisone equivalent or less)
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients must not have grade 2 neuropathy or greater, within 14 days prior to registration

Who cannot join

None listed.

Trial locations and contacts

207 sites in 1 country.

207 sites in 1 country

United States207 sites

  • Hawaii Cancer Care - Westridge

    ‘Aiea, Hawaii, 96701

  • The Queen's Medical Center - West Oahu

    ‘Ewa Beach, Hawaii, 96706

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • 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

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

  • ThedaCare Regional Cancer Center

    Appleton, Wisconsin, 54911

  • 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

  • Nebraska Medicine-Bellevue

    Bellevue, Nebraska, 68123

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • ThedaCare Cancer Care - Berlin

    Berlin, Wisconsin, 54923

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • 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

  • 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

  • University of Michigan - Brighton Center for Specialty Care

    Brighton, Michigan, 48116

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • 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

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • 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

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Advocate Illinois Masonic Medical Center

    Chicago, Illinois, 60657

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Kootenai Health - Coeur d'Alene

    Coeur d'Alene, Idaho, 83814

  • Baptist Memorial Hospital and Cancer Center-Collierville

    Collierville, Tennessee, 38017

  • Baptist Memorial Hospital and Cancer Center-Golden Triangle

    Columbus, Mississippi, 39705

  • UT MD Anderson - The Woodlands

    Conroe, Texas, 77384

  • 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

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • 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

  • Advocate Good Samaritan Hospital

    Downers Grove, Illinois, 60515

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Pocono Medical Center

    East Stroudsburg, Pennsylvania, 18301

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Swedish Cancer Institute-Edmonds

    Edmonds, Washington, 98026

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Advocate Sherman Hospital

    Elgin, Illinois, 60123

  • UPMC Hillman Cancer Center Erie

    Erie, Pennsylvania, 16505

  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Parkland Health Center - Farmington

    Farmington, Missouri, 63640

  • 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

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Northwestern Medicine Glenview Outpatient Center

    Glenview, Illinois, 60026

  • Aurora Cancer Care-Grafton

    Grafton, Wisconsin, 53024

  • Northwestern Medicine Grayslake Outpatient Center

    Grayslake, Illinois, 60030

  • 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

  • Baptist Cancer Center-Grenada

    Grenada, Mississippi, 38901

  • Advocate South Suburban Hospital

    Hazel Crest, Illinois, 60429

  • Lehigh Valley Hospital-Hazleton

    Hazleton, Pennsylvania, 18201

  • Essentia Health Hibbing Clinic

    Hibbing, Minnesota, 55746

  • Hawaii Cancer Care Inc - Waterfront Plaza

    Honolulu, Hawaii, 96813

  • Queen's Cancer Cenrer - POB I

    Honolulu, Hawaii, 96813

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Queen's Cancer Center - Kuakini

    Honolulu, Hawaii, 96817

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • UT MD Anderson - West Houston

    Houston, Texas, 77079

  • Swedish Cancer Institute-Issaquah

    Issaquah, Washington, 98029

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro

    Jonesboro, Arkansas, 72401

  • Logan Health Medical Center

    Kalispell, Montana, 59901

  • Aurora Cancer Care-Kenosha South

    Kenosha, Wisconsin, 53142

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Northwestern Medicine Lake Forest Hospital

    Lake Forest, Illinois, 60045

  • 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, 89183

  • UT MD Anderson - League City

    League City, Texas, 77573

  • 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

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Henry Ford Saint John Hospital - Macomb Medical

    Macomb, Michigan, 48044

  • Saint John's Hospital - Healtheast

    Maplewood, Minnesota, 55109

  • Aurora Bay Area Medical Group-Marinette

    Marinette, Wisconsin, 54143

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

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

    Mechanicsburg, Pennsylvania, 17050

  • Baptist Memorial Hospital and Cancer Center-Memphis

    Memphis, Tennessee, 38120

  • 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

  • University of South Alabama Mitchell Cancer Institute

    Mobile, Alabama, 36688

  • UPMC Hillman Cancer Center - Monroeville

    Monroeville, Pennsylvania, 15146

  • West Virginia University Healthcare

    Morgantown, West Virginia, 26506

  • Saint Alphonsus Cancer Care Center-Nampa

    Nampa, Idaho, 83687

  • Saint Luke's Cancer Institute - Nampa

    Nampa, Idaho, 83687

  • ThedaCare Regional Medical Center - Neenah

    Neenah, Wisconsin, 54956

  • Baptist Memorial Hospital and Cancer Center-Union County

    New Albany, Mississippi, 38652

  • UC Comprehensive Cancer Center at Silver Cross

    New Lenox, Illinois, 60451

  • Cancer Care Center of O'Fallon

    O'Fallon, Illinois, 62269

  • Advocate Christ Medical Center

    Oak Lawn, Illinois, 60453-2699

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Nebraska Medicine-Village Pointe

    Omaha, Nebraska, 68118

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Saint Alphonsus Cancer Care Center-Ontario

    Ontario, Oregon, 97914

  • Northwestern Medicine Orland Park

    Orland Park, Illinois, 60462

  • University of Chicago Medicine-Orland Park

    Orland Park, Illinois, 60462

  • Vince Lombardi Cancer Clinic - Oshkosh

    Oshkosh, Wisconsin, 54904

  • Baptist Memorial Hospital and Cancer Center-Oxford

    Oxford, Mississippi, 38655

  • Advocate Lutheran General Hospital

    Park Ridge, Illinois, 60068

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UPMC-Passavant Hospital

    Pittsburgh, Pennsylvania, 15237

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

  • Trinity Health Saint Joseph Mercy Oakland Hospital

    Pontiac, Michigan, 48341

  • Kootenai Clinic Cancer Services - Post Falls

    Post Falls, Idaho, 83854

  • Aurora Cancer Care-Racine

    Racine, Wisconsin, 53406

  • Renown Regional Medical Center

    Reno, Nevada, 89502

  • Valley Medical Center

    Renton, Washington, 98055

  • Virginia Cancer Institute

    Richmond, Virginia, 23229

  • VCU Massey Cancer Center at Stony Point

    Richmond, Virginia, 23235

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Corewell Health William Beaumont University Hospital

    Royal Oak, Michigan, 48073

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Sainte Genevieve County Memorial Hospital

    Sainte Genevieve, Missouri, 63670

  • Kootenai Clinic Cancer Services - Sandpoint

    Sandpoint, Idaho, 83864

  • Essentia Health Sandstone

    Sandstone, Minnesota, 55072

  • Swedish Medical Center-First Hill

    Seattle, Washington, 98122

  • 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

  • Baptist Memorial Hospital and Cancer Center-Desoto

    Southhaven, Mississippi, 38671

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

  • Springfield Clinic

    Springfield, Illinois, 62702

  • Springfield Memorial Hospital

    Springfield, Illinois, 62781

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Missouri Baptist Medical Center

    St Louis, Missouri, 63131

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • UT MD Anderson - Sugar Land

    Sugar Land, Texas, 77478

  • Missouri Baptist Sullivan Hospital

    Sullivan, Missouri, 63080

  • Aurora Medical Center in Summit

    Summit, Wisconsin, 53066

  • Corewell Health Beaumont Troy Hospital

    Troy, Michigan, 48085

  • Upper Valley Medical Center

    Troy, Ohio, 45373

  • Vince Lombardi Cancer Clinic-Two Rivers

    Two Rivers, Wisconsin, 54241

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • Essentia Health Virginia Clinic

    Virginia, Minnesota, 55792

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

  • UI Health Care Mission Cancer and Blood - Waukee Clinic

    Waukee, Iowa, 50263

  • Aurora Cancer Care-Milwaukee West

    Wauwatosa, Wisconsin, 53226

  • Aurora West Allis Medical Center

    West Allis, Wisconsin, 53227

  • Presbyterian Intercommunity Hospital

    Whittier, California, 90602

  • Huron Gastroenterology PC

    Ypsilanti, Michigan, 48106

  • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

    Ypsilanti, Michigan, 48197

Other trials in United States

About this study

Official title: FOLFOX in Combination With Binimetinib as 2nd Line Therapy for Patients With Advanced Biliary Tract Cancers With MAPK Pathway Alterations: A ComboMATCH Treatment Trial

This phase II ComboMATCH treatment trial compares the usual treatment of modified leucovorin, fluorouracil and oxaliplatin (mFOLFOX6) chemotherapy to using binimetinib plus mFOLFOX6 chemotherapy to shrink tumors in patients with biliary tract cancers that have spread to other places in the body (advanced) and had progression of cancer after previous treatments (2nd line setting). Fluorouracil is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It works by killing tumor cells. Leucovorin may help the other drugs in the mFOLFOX6 chemotherapy regimen work better by making tumor cells more sensitive to the drugs. Binimetinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals tumor cells to multiply. This helps to stop or slow the spread of tumor cells. Giving binimetinib in combination with mFOLFOX6 chemotherapy may be effective in shrinking or stabilizing advanced biliary tract cancers in the 2nd line setting.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine whether binimetinib and mFOLFOX6 combination therapy improves overall survival (OS) compared to mFOLFOX6 alone in patients with advanced/recurrent biliary tract cancer (BTC) and with alterations in RAS/RAF/MEK/ERK pathway, who have progressed on one prior line of therapy.

SECONDARY OBJECTIVES:

  1. To determine whether binimetinib and mFOLFOX6 combination therapy improves objective response rate (ORR) compared to FOLFOX alone.

II. To determine if clinical outcomes including progression free survival (PFS), duration of response (DOR), and disease control rate (DCR) are improved with combination treatment of binimetinib and mFOLFOX6 compared to FOLFOX alone in patients with advanced/recurrent BTC and with alterations in RAS/RAF/MEK/ERK pathway who have progression on one prior line of therapy.

III. Toxicity and tolerability will be evaluated within and between the two treatment arms, where frequency, type, and severity of adverse events will be assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v)5.0.

IV. 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 (ctDNA) mutation profile from plasma, as described in ComboMATCH Registration Protocol.

EXPLORATORY OBJECTIVES:

  1. Generate a prognostic model of MAPK mutations for this patient population using clinical, laboratory and molecular features of their disease and clinical outcome to validate on future samples.

II. Correlation of outcome with albumin. III. Assess the correlation between the presence of MAPK pathway mutations and activity of addition of binimetinib therapy to standard 2nd line chemotherapy.

IV. Conduct whole-exome sequencing and ribonucleic acid (RNA)-sequencing at baseline, and on optional biopsy upon progression to assess determinants of response and resistance.

  1. Explore changes in plasma MAPK mutations allelic burden and other molecular findings at baseline and upon progression using ctDNA and correlate changes with clinical activity, disease course as well as response/resistance to therapy.

VI. Evaluate if our machine learning algorithm for RAS/RAF/MEK/ERK pathway mutations correlates with detection of mutations as well as prediction of outcomes from samples obtained in this study.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients receive leucovorin intravenously (IV) over 2 hours and oxaliplatin IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-2. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood during screening and on study, and undergo computed tomography (CT) with contrast, magnetic resonance imaging (MRI), or fludeoxyglucose F-18 positron emission tomography (FDG-PET) throughout the trial as clinically indicated. Patients may also undergo bone scans on study and may undergo biopsies throughout the study as clinically indicated.

ARM 2: Patients receive binimetinib orally (PO) on days 1-14, and leucovorin IV, oxaliplatin IV, and fluorouracil IV as in Arm 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiogram (ECHO) or multigated acquisition scan (MUGA) and collection of blood during screening and on study, and undergo CT with contrast, MRI, or FDG-PET throughout the trial as clinically indicated. Patients may also undergo bone scans on study and may undergo biopsies throughout the study as clinically indicated.

After completion of study treatment, patients are followed up every 8 weeks until disease progression, thereafter patients are followed for survival every 4 months for up to 5 years following registration.

Being tested
Binimetinib, Biopsy Procedure, Biospecimen Collection, Bone Scan, Computed Tomography
Medical subject headings
Gallbladder Neoplasms, Cholangiocarcinoma, Klatskin Tumor

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 biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood

  • 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

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Given IV

  • Leucovorin CalciumDrug

    Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate

    Given IV

  • 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

  • OxaliplatinDrug

    Also called 1-OHP, Ai Heng, Aiheng, Dacotin

    Given IV

Study groups in NCT05564403
Study groupRoleWhat they receive
Arm 1 (mFOLFOX6)Active comparatorPatients receive leucovorin IV over 2 hours and oxaliplatin IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-2. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood during screening and on study, and undergo CT with contrast, MRI, or FDG-PET throughout the trial as clinically indicated. Patients may also undergo bone scans on study and may undergo biopsies throughout the study as clinically indicated.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Leucovorin Calcium; Procedure: Magnetic Resonance Imaging; Drug: Oxaliplatin
Arm 2 (binimetinib, mFOLFOX6)ExperimentalPatients receive binimetinib PO on days 1-14, and leucovorin IV, oxaliplatin IV, and fluorouracil IV as in Arm 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA and collection of blood during screening and on study, and undergo CT with contrast, MRI, or FDG-PET throughout the trial as clinically indicated. Patients may also undergo bone scans on study and may undergo biopsies throughout the study as clinically indicated.
Receives: Drug: Binimetinib; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Echocardiography Test; Drug: Fluorouracil; Drug: Leucovorin Calcium; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Drug: Oxaliplatin

What is being measured

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

  1. Overall survival (OS)

    The primary efficacy analysis will be to compare the OS distributions between those treated with modified leucovorin, fluorouracil and oxaliplatin (mFOLFOX6) and binimetinib versus (vs.) mFOLFOX6. Despite being a randomized phase II trial, we will utilize an intent to treat approach such that patients will be analyzed based on the treatment arm to which they were randomized. As defined above, OS will be compared between the two treatment arms using Kaplan-Meier methods. The hazard ratio, median OS, and estimated OS rates at 6, 12, 18, 24, and 30 months will be estimated along with corresponding 95% confidence intervals. Anticipating that the treatment arms will be balanced in terms of the potential confounders reflect in the stratification factors, a log-rank test will be used to compare the OS distributions between the two treatment arms in this cohort.

    Measured: From randomization to the time of death due to any cause, assessed up to 30 months

Secondary outcomes (5)

  1. Objective response

    Objective response by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria will be estimated using objective response rate (ORR) where ORR is defined as the number of evaluable patients achieving a response (partial response [PR] or complete response [CR] per RECIST v1.1) during treatment with study therapy divided by the total number of evaluable patients. Rates of response will be compared across arms using a Chi-Square Test for Proportion. Point estimates will be generated for objective response rates within each arm along with 95% confidence intervals using the Clopper-Pearson method.

    Measured: Up to 5 years

  2. Progression free survival (PFS)

    Disease progression will be determined based on RECIST 1.1 criteria. PFS will be estimated using the Kaplan-Meier method. The median PFS and 95% confidence interval will be reported. Patients will be censored at the last disease assessment date.

    Measured: From study entry to the first of either disease progression or death from any cause, assessed up to 5 years

  3. Duration of response (DoR)

    Defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented, or death if no prior evidence of disease progression. The distribution of DoR will be estimated using the method of Kaplan-Meier.

    Measured: Up to 5 years

  4. Clinical benefit

    Defined as achieving CR, PR, or stable disease (SD) for at least 4 months while on treatment. Disease status will be assessed using RECIST v. 1.1 criteria. Clinical benefit rate (CBR) will be calculated as the proportion of evaluable patients who achieve clinical benefit. The final CBR point estimate and corresponding 95% confidence interval calculated using Clopper-Pearson method.

    Measured: Up to 5 years

  5. Incidence of adverse events

    Patients will be evaluated for adverse events using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events version 5.0. Summary statistics (e.g., mean, median, standard deviation) and frequency tables will be used to describe the distributions of adverse events. Rates of adverse events occurring in the treatment arm will be compared to the control arm with chi-squared tests (or suitable alternative) used for comparisons where applicable. Tolerability will also be evaluated, summarizing rates of dose delays or modifications, reasons patients end treatment, and time to end of active treatment.

    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 posted3 Oct 2022
  2. Study start9 Feb 2024
  3. Primary completion8 Aug 2026
  4. Study completion15 Oct 2027 (estimated)

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
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05564403
Sponsor's protocol ID
NCI-2022-07833
Other IDs
NCI-2022-07833, EAY191-A6, EAY191-A6, U10CA180821
Status last verified
Oct 2026
First submitted
27 Sep 2022
Last updated
19 Oct 2026
Results posted
No
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.

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