AzTrials
AzTrials

Metastatic Colon AdenocarcinomaPhase 2NCT05308446

Testing the Addition of Nivolumab to Standard Treatment for Patients With Metastatic or Unresectable Colorectal Cancer That Have a BRAF Mutation

A Phase 2 study testing Cetuximab, Encorafenib and Nivolumab in people with Metastatic Colon Adenocarcinoma and Metastatic Rectal Adenocarcinoma, run by National Cancer Institute (NCI) at 286 sites in 2 countries.

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 trial tests whether adding nivolumab to the usual treatment (encorafenib and cetuximab) works better than the usual treatment alone to shrink tumors in patients with colorectal cancer that has spread to other places in the body (metastatic) or that cannot be removed by surgery (unresectable) and whose… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cetuximab, Encorafenib and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
86 participants
Where
286 sitesin 2 countries
Study dates
19 Jul 2022to 1 Jun 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Participants must have a histologically or cytologically confirmed diagnosis of adenocarcinoma of the colon or rectum. The date of diagnosis will be determined according to the pathologic date of diagnosis
  • Participants must have measurable disease according to RECIST1.1 criteria. Computed tomography (CT) scans or magnetic resonance imaging (MRIs) used to assess measurable disease must have been completed within 28 days prior to registration. CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form
  • Participants must have documented unresectable and/or metastatic disease on CT or MRI imaging. All disease must be assessed and documented on the Baseline Tumor Assessment Form
  • Participants must have BRAF^V600E mutated colorectal cancer as tested in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
  • Participants must have proficient mismatch repair (pMMR) or microsatellite stable (MSS) status as tested in a CLIA-certified laboratory and documented by the treating clinician. Proficient mismatch repair status can be determined by intact expression by immunohistochemistry of all 4 mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2). Microsatellite instability can be determined by polymerase chain reaction (PCR)
  • Participants with brain metastases must have completed surgery or radiation therapy >= 28 days prior to registration. These participants must have a CT or MRI of the brain showing no new or enlarging lesions within 42 days prior to registration. These participants must also be neurologically asymptomatic and without corticosteroid treatment for at least 7 days prior to registration. Metastatic brain parenchymal disease must have been treated and participant must be off steroids for 7 days prior to registration. The presence of leptomeningeal disease (LMD) is not considered stable disease, and participants with LMD are not eligible for this study
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  • Participants with known evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to registration
  • Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to registration
  • Participants must have had one or two prior regimens of systemic chemotherapy for metastatic or locally advanced, unresectable disease. (A maintenance regimen of 5-fluorouracil or capecitabine, with or without bevacizumab, should not be counted as a separate line of treatment. The re-introduction of an initially successful induction regimen will not be counted as one additional line of treatment). Prior treatment for metastatic disease is not required for patients who experienced disease recurrence during or within 6 months of completion of adjuvant chemotherapy
  • Participants must be of age >= 18 years at the time of informed consent
  • Participants must have a Zubrod performance status of 0 or 1
  • Participants must have a complete medical history and physical exam within 28 days prior to registration
  • Absolute neutrophil count >= 1.0 x 10^3/uL (within 28 days prior to registration)
  • Hemoglobin >= 9 g/dL (within 28 days prior to registration)
  • Platelets >= 75 x 10^3/uL (within 28 days prior to registration)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to registration)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to registration)
  • If liver metastases are present, then it is acceptable for AST level =< 5.0 x ULN, and/or an ALT level =< 5.0 x ULN (within 28 days prior to registration)
  • Participants must have serum creatinine =< the IULN OR measured OR calculated creatinine clearance >= 50 mL/min using the Cockroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
  • Participants must be able to swallow and retain pills
  • Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2 or better
  • Participants with a known significant risk of corrected QT interval (QTc) prolongation must have an electrocardiogram (ECG) performed within 28 days prior to prior to registration
  • Note: Per package insert for encorafenib, participants already at risk for development of QTc prolongation include those who "already have or who are at significant risk of developing QTc prolongation, including participants with known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure and those taking other medicinal products associated with QT prolongation."
  • Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
  • Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.
  • Note: As a part of the OPEN registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Who cannot join

  • Participants must not have a known positive serology for human immunodeficiency virus (HIV). Encorafenib is contraindicated with concomitant use of non-nucleoside analog reverse transcriptase inhibitors like efavirenz and etravirine. In addition, it is recommended in the investigator brochure of encorafenib to avoid using encorafenib with protease inhibitors. Therefore, because all participants on this study would receive encorafenib for either randomized arm of treatment, participants with HIV who receive these components of highly active antiretroviral therapy (HAART) would be at high risk for complications of drug-drug interaction
  • Participants must not have had prior treatment with a BRAF inhibitor (including, but not limited to, encorafenib, dabrafenib, or vemurafenib), MEK inhibitor (including, but not limited to, trametinib, selumetinib, or binimetinib), or ERK inhibitor (of note, regorafenib is not considered a BRAF inhibitor for the context of eligibility criteria)
  • Participants must not have had prior treatment with anti-EGFR therapies
  • Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
  • Participants must not have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if < 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted, as long as there has been a washout period for corticosteroids of >= 7 days prior to registration
  • Participants must not have received a live vaccine within 30 days prior to study registration. Seasonal flu and COVID vaccines that do not contain a live virus are permitted
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  • Participants must not be receiving any other investigational agents
  • Participants must not have impaired gastrointestinal function or disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption)
  • Participants must not have a history of inflammatory bowel disease, (including ulcerative colitis and Crohn's disease), symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and myasthenia gravis, multiple sclerosis).
  • Note: Participants with Graves' disease will be allowed
  • Participants must not have a history of pneumonitis that has required oral or intravenous (IV) steroids within the last 12 months
  • Participants must not have a history of a grade 3 or 4 allergic reaction attributed to humanized or human monoclonal antibody therapy
  • Participants must not have a history of a prior allogeneic tissue or solid organ transplant
  • Participants must not have a history of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) within 6 months prior to study registration
  • Participants must not have uncontrolled blood pressure and hypertension within 28 days prior to registration.
  • Uncontrolled blood pressure and hypertension is defined as systolic blood pressure (SBP) >= 160 mmHg or diastolic blood pressure (DBP) > 100 mmHg within 28 days prior to registration. Participants are permitted to be receiving multiple anti-hypertensive medications (unless otherwise indicated in the study). All blood pressure measurements within the 28 days prior to registration must be SBP < 160 and DBP =< 100. An exception can be made by a healthcare provider for a participant with a single blood pressure elevation who upon rechecking has a normal blood pressure
  • Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen or requires concurrent therapy
  • Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion and vasectomy with testing showing no sperm in the semen
  • Participants must not be planning treatment with other systemic anti-cancer agents (e.g., chemotherapy, hormonal therapy, immunotherapy) or other treatments not part of protocol-specified anti-cancer therapy including concurrent investigational agents of any type

Trial locations and contacts

286 sites in 2 countries.

286 sites in 2 countries

United States282 sites

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • The Don and Sybil Harrington Cancer Center

    Amarillo, Texas, 79106

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • Community Hospital of Anaconda

    Anaconda, Montana, 59711

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • ThedaCare Regional Cancer Center

    Appleton, Wisconsin, 54911

  • Duluth Clinic Ashland

    Ashland, Wisconsin, 54806

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • Advocate Good Shepherd Hospital

    Barrington, Illinois, 60010

  • LSU Health Baton Rouge-North Clinic

    Baton Rouge, Louisiana, 70805

  • Our Lady of the Lake Physician Group

    Baton Rouge, Louisiana, 70808

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • Strecker Cancer Center-Belpre

    Belpre, Ohio, 45714

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • Prisma Health Cancer Institute - Spartanburg

    Boiling Springs, South Carolina, 29316

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • McFarland Clinic - Boone

    Boone, Iowa, 50036

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • United Hospital Center

    Bridgeport, West Virginia, 26330

  • Trinity Health IHA Medical Group Hematology Oncology - Brighton

    Brighton, Michigan, 48114

  • Trinity Health Medical Center - Brighton

    Brighton, Michigan, 48114

  • 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

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • 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

  • Mercy Cancer Center - Carmichael

    Carmichael, California, 95608

  • Mercy San Juan Medical Center

    Carmichael, California, 95608

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Chelsea Hospital

    Chelsea, Michigan, 48118

  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

    Chelsea, Michigan, 48118

  • University of Illinois

    Chicago, Illinois, 60612

  • Advocate Illinois Masonic Medical Center

    Chicago, Illinois, 60657

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

  • Southeastern Medical Oncology Center-Clinton

    Clinton, North Carolina, 28328

  • Kootenai Health - Coeur d'Alene

    Coeur d'Alene, Idaho, 83814

  • Rocky Mountain Cancer Centers-Penrose

    Colorado Springs, Colorado, 80907

  • UCHealth Memorial Hospital Central

    Colorado Springs, Colorado, 80909

  • Memorial Hospital North

    Colorado Springs, Colorado, 80920

  • Mount Carmel East Hospital

    Columbus, Ohio, 43213

  • Columbus Oncology and Hematology Associates Inc

    Columbus, Ohio, 43214

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Grant Medical Center

    Columbus, Ohio, 43215

  • The Mark H Zangmeister Center

    Columbus, Ohio, 43219

  • Doctors Hospital

    Columbus, Ohio, 43228

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Ochsner Hematology Oncology North Shore - Covington (West Region)

    Covington, Louisiana, 70433

  • Northwest Cancer Center - Crown Point

    Crown Point, Indiana, 46307

  • AMG Crystal Lake - Oncology

    Crystal Lake, Illinois, 60014

  • Aurora Saint Luke's South Shore

    Cudahy, Wisconsin, 53110

  • UT Southwestern Simmons Cancer Center - RedBird

    Dallas, Texas, 75237

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • 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

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Essentia Health - Deer River Clinic

    Deer River, Minnesota, 56636

  • Delaware Health Center-Grady Cancer Center

    Delaware, Ohio, 43015

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Henry Ford Health Saint John Hospital

    Detroit, Michigan, 48236

  • Illinois CancerCare-Dixon

    Dixon, Illinois, 61021

  • Advocate Good Samaritan Hospital

    Downers Grove, Illinois, 60515

  • Kaiser Permanente Dublin

    Dublin, California, 94568

  • Columbus Oncology and Hematology Associates

    Dublin, Ohio, 43016

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Northwest Oncology LLC

    Dyer, Indiana, 46311

  • Prisma Health Cancer Institute - Easley

    Easley, South Carolina, 29640

  • Henry Ford River District Hospital

    East China Township, Michigan, 48054

  • Marshfield Medical Center-EC Cancer Center

    Eau Claire, Wisconsin, 54701

  • 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

  • Mercy Cancer Center - Elk Grove

    Elk Grove, California, 95758

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • Hunterdon Medical Center

    Flemington, New Jersey, 08822

  • 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

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Cancer Care and Hematology-Fort Collins

    Fort Collins, Colorado, 80528

  • McFarland Clinic - Trinity Cancer Center

    Fort Dodge, Iowa, 50501

  • UT Southwestern/Simmons Cancer Center-Fort Worth

    Fort Worth, Texas, 76104

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Dayton Physicians LLC-Atrium

    Franklin, Ohio, 45005

  • Kaiser Permanente-Fremont

    Fremont, California, 94538

  • Kaiser Permanente-Fresno

    Fresno, California, 93720

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Southeastern Medical Oncology Center-Goldsboro

    Goldsboro, North Carolina, 27534

  • CTCA at Western Regional Medical Center

    Goodyear, Arizona, 85338

  • Aurora Cancer Care-Grafton

    Grafton, Wisconsin, 53024

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • UCHealth Greeley Hospital

    Greeley, Colorado, 80631

  • Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311

  • Miami Valley Cancer Care and Infusion

    Greenville, Ohio, 45331

  • Prisma Health Cancer Institute - Butternut

    Greenville, South Carolina, 29605

  • Prisma Health Cancer Institute - Faris

    Greenville, South Carolina, 29605

  • Prisma Health Greenville Memorial Hospital

    Greenville, South Carolina, 29605

  • Prisma Health Cancer Institute - Eastside

    Greenville, South Carolina, 29615

  • Prisma Health Cancer Institute - Greer

    Greer, South Carolina, 29650

  • Henry Ford Saint John Hospital - Academic

    Grosse Pointe Woods, Michigan, 48236

  • Henry Ford Saint John Hospital - Van Elslander

    Grosse Pointe Woods, Michigan, 48236

  • Mount Carmel Grove City Hospital

    Grove City, Ohio, 43123

  • Advocate South Suburban Hospital

    Hazel Crest, Illinois, 60429

  • Essentia Health Hibbing Clinic

    Hibbing, Minnesota, 55746

  • UCHealth Highlands Ranch Hospital

    Highlands Ranch, Colorado, 80129

  • Northwest Cancer Center - Hobart

    Hobart, Indiana, 46342

  • Saint Mary Medical Center

    Hobart, Indiana, 46342

  • Kaiser Permanente Moanalua Medical Center

    Honolulu, Hawaii, 96819

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • Franciscan Health Indianapolis

    Indianapolis, Indiana, 46237

  • Saint Catherine Hospital

    Indianapolis, Indiana, 46312

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

    Irvine, California, 92612

  • Swedish Cancer Institute-Issaquah

    Issaquah, Washington, 98029

  • Southeastern Medical Oncology Center-Jacksonville

    Jacksonville, North Carolina, 28546

  • McFarland Clinic - Jefferson

    Jefferson, Iowa, 50129

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Beacon Kalamazoo Cancer Center

    Kalamazoo, Michigan, 49009

  • Logan Health Medical Center

    Kalispell, Montana, 59901

  • Aurora Cancer Care-Kenosha South

    Kenosha, Wisconsin, 53142

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Illinois CancerCare-Kewanee Clinic

    Kewanee, Illinois, 61443

  • Franciscan Saint Elizabeth Health - Lafayette East

    Lafayette, Indiana, 47905

  • Fairfield Medical Center

    Lancaster, Ohio, 43130

  • University of Michigan Health - Sparrow Lansing

    Lansing, Michigan, 48912

  • Cancer Centers of Southwest Oklahoma Research

    Lawton, Oklahoma, 73505

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • AMG Libertyville - Oncology

    Libertyville, Illinois, 60048

  • Condell Memorial Hospital

    Libertyville, Illinois, 60048

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

  • Medical Center of the Rockies

    Loveland, Colorado, 80538

  • Illinois CancerCare-Macomb

    Macomb, Illinois, 61455

  • Henry Ford Saint John Hospital - Macomb Medical

    Macomb, Michigan, 48044

  • OhioHealth Mansfield Hospital

    Mansfield, Ohio, 44903

  • Aurora Bay Area Medical Group-Marinette

    Marinette, Wisconsin, 54143

  • OhioHealth Marion General Hospital

    Marion, Ohio, 43302

  • McFarland Clinic - Marshalltown

    Marshalltown, Iowa, 50158

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Memorial Hospital

    Marysville, Ohio, 43040

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Saint Luke's Cancer Institute - Meridian

    Meridian, Idaho, 83642

  • Woodland Cancer Care Center

    Michigan City, Indiana, 46360

  • 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

  • Marshfield Medical Center - Minocqua

    Minocqua, Wisconsin, 54548

  • Community Medical Center

    Missoula, Montana, 59804

  • Kaiser Permanente-Modesto

    Modesto, California, 95356

  • Franciscan Health Mooresville

    Mooresville, Indiana, 46158

  • West Virginia University Healthcare

    Morgantown, West Virginia, 26506

  • Knox Community Hospital

    Mount Vernon, Ohio, 43050

  • ProHealth D N Greenwald Center

    Mukwonago, Wisconsin, 53149

  • The Community Hospital

    Munster, Indiana, 46321

  • Women's Diagnostic Center - Munster

    Munster, Indiana, 46321

  • Trinity Health Muskegon Hospital

    Muskegon, Michigan, 49444

  • Saint Alphonsus Cancer Care Center-Nampa

    Nampa, Idaho, 83687

  • Saint Luke's Cancer Institute - Nampa

    Nampa, Idaho, 83687

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • Cancer Center of Western Wisconsin

    New Richmond, Wisconsin, 54017

  • Licking Memorial Hospital

    Newark, Ohio, 43055

  • Providence Newberg Medical Center

    Newberg, Oregon, 97132

  • CTCA at Southeastern Regional Medical Center

    Newnan, Georgia, 30265

  • Corewell Health Lakeland Hospitals - Niles Hospital

    Niles, Michigan, 49120

  • Cancer and Hematology Centers of Western Michigan - Norton Shores

    Norton Shores, Michigan, 49444

  • Henry Ford Health Providence Novi Hospital

    Novi, Michigan, 48374

  • Henry Ford Medical Center-Columbus

    Novi, Michigan, 48377

  • Cancer Care Center of O'Fallon

    O'Fallon, Illinois, 62269

  • Advocate Christ Medical Center

    Oak Lawn, Illinois, 60453-2699

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • ProHealth Oconomowoc Memorial Hospital

    Oconomowoc, Wisconsin, 53066

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Mercy Hospital Oklahoma City

    Oklahoma City, Oklahoma, 73120

  • Saint Alphonsus Cancer Care Center-Ontario

    Ontario, Oregon, 97914

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • Providence Willamette Falls Medical Center

    Oregon City, Oregon, 97045

  • Vince Lombardi Cancer Clinic - Oshkosh

    Oshkosh, Wisconsin, 54904

  • Illinois CancerCare-Ottawa Clinic

    Ottawa, Illinois, 61350

  • Advocate Lutheran General Hospital

    Park Ridge, Illinois, 60068

  • Illinois CancerCare-Pekin

    Pekin, Illinois, 61554

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • Illinois CancerCare-Peru

    Peru, Illinois, 61354

  • University of Pennsylvania/Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • FirstHealth of the Carolinas-Moore Regional Hospital

    Pinehurst, North Carolina, 28374

  • 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

  • Illinois CancerCare-Princeton

    Princeton, Illinois, 61356

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Aurora Cancer Care-Racine

    Racine, Wisconsin, 53406

  • Corewell Health Reed City Hospital

    Reed City, Michigan, 49677

  • Marshfield Medical Center-Rice Lake

    Rice Lake, Wisconsin, 54868

  • UT Southwestern Clinical Center at Richardson/Plano

    Richardson, Texas, 75080

  • North Memorial Medical Health Center

    Robbinsdale, Minnesota, 55422

  • Mercy Cancer Center - Rocklin

    Rocklin, California, 95765

  • Kaiser Permanente-Roseville

    Roseville, California, 95661

  • Kaiser Permanente Downtown Commons

    Sacramento, California, 95814

  • Mercy Cancer Center - Sacramento

    Sacramento, California, 95816

  • Kaiser Permanente-South Sacramento

    Sacramento, California, 95823

  • MyMichigan Medical Center Saginaw

    Saginaw, Michigan, 48601

  • Oncology Hematology Associates of Saginaw Valley PC

    Saginaw, Michigan, 48604

  • Dartmouth Cancer Center - North

    Saint Johnsbury, Vermont, 05819

  • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

    Saint Joseph, Michigan, 49085

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Kaiser Permanente-San Francisco

    San Francisco, California, 94115

  • Kaiser Permanente-Santa Teresa-San Jose

    San Jose, California, 95119

  • Kaiser Permanente San Leandro

    San Leandro, California, 94577

  • Kootenai Clinic Cancer Services - Sandpoint

    Sandpoint, Idaho, 83864

  • Essentia Health Sandstone

    Sandstone, Minnesota, 55072

  • Kaiser Permanente Medical Center - Santa Clara

    Santa Clara, California, 95051

  • Kaiser Permanente-Santa Rosa

    Santa Rosa, California, 95403

  • Swedish Medical Center-First Hill

    Seattle, Washington, 98122

  • Prisma Health Cancer Institute - Seneca

    Seneca, South Carolina, 29672

  • Vince Lombardi Cancer Clinic-Sheboygan

    Sheboygan, Wisconsin, 53081

  • Kaiser Permanente-South San Francisco

    South San Francisco, California, 94080

  • Henry Ford Health Providence Southfield Hospital

    Southfield, Michigan, 48075

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

  • Springfield Clinic

    Springfield, Illinois, 62702

  • Springfield Memorial Hospital

    Springfield, Illinois, 62781

  • Springfield Regional Cancer Center

    Springfield, Ohio, 45504

  • Springfield Regional Medical Center

    Springfield, Ohio, 45504

  • Bhadresh Nayak MD PC-Sterling Heights

    Sterling Heights, Michigan, 48312

  • Marshfield Medical Center-River Region at Stevens Point

    Stevens Point, Wisconsin, 54482

  • Aurora Medical Center in Summit

    Summit, Wisconsin, 53066

  • MyMichigan Medical Center Tawas

    Tawas City, Michigan, 48764

  • Toledo Clinic Cancer Centers-Toledo

    Toledo, Ohio, 43623

  • Munson Medical Center

    Traverse City, Michigan, 49684

  • 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

  • Kaiser Permanente-Vallejo

    Vallejo, California, 94589

  • Northwest Cancer Center - Valparaiso

    Valparaiso, Indiana, 46383

  • Essentia Health Virginia Clinic

    Virginia, Minnesota, 55792

  • Kaiser Permanente-Walnut Creek

    Walnut Creek, California, 94596

  • Henry Ford Health Warren Hospital

    Warren, Michigan, 48093

  • Henry Ford Warren Hospital - GLCMS

    Warren, Michigan, 48093

  • Macomb Hematology Oncology PC

    Warren, Michigan, 48093

  • Illinois CancerCare - Washington

    Washington, Illinois, 61571

  • UW Cancer Center at ProHealth Care

    Waukesha, Wisconsin, 53188

  • Aurora Cancer Care-Milwaukee West

    Wauwatosa, Wisconsin, 53226

  • Aurora West Allis Medical Center

    West Allis, Wisconsin, 53227

  • Henry Ford West Bloomfield Hospital

    West Bloomfield, Michigan, 48322

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

    West Branch, Michigan, 48661

  • Reading Hospital

    West Reading, Pennsylvania, 19611

  • Saint Ann's Hospital

    Westerville, Ohio, 43081

  • Marshfield Medical Center - Weston

    Weston, Wisconsin, 54476

  • Woodland Memorial Hospital

    Woodland, California, 95695

  • University of Michigan Health - West

    Wyoming, Michigan, 49519

  • Rush-Copley Healthcare Center

    Yorkville, Illinois, 60560

  • 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

  • Centro Comprensivo de Cancer de UPR

    San Juan, 00927

  • PROncology

    San Juan, 00927

  • San Juan City Hospital

    San Juan, 00936

Other trials in Puerto Rico

About this study

Official title: Randomized Phase II Trial of Encorafenib and Cetuximab With or Without Nivolumab (NSC #748726) for Patients With Previously Treated, Microsatellite Stable, BRAFV600E Metastatic and/or Unresectable Colorectal Cancer

This phase II trial tests whether adding nivolumab to the usual treatment (encorafenib and cetuximab) works better than the usual treatment alone to shrink tumors in patients with colorectal cancer that has spread to other places in the body (metastatic) or that cannot be removed by surgery (unresectable) and whose tumor has a mutation in a gene called BRAF. Encorafenib is in a class of medications called kinase inhibitors. It is used in patients whose cancer has a certain mutation (change) in the BRAF gene. It works by blocking the action of mutated BRAF that signals cancer cells to multiply. This helps to stop or slow the spread of cancer cells. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of cancer cells. This may help keep cancer cells from growing. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab in combination with encorafenib and cetuximab may be more effective than encorafenib and cetuximab alone at stopping tumor growth and spreading in patients with metastatic or unresectable BRAF-mutant colorectal cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in patients with microsatellite stable (MSS), BRAF^V600E metastatic and/or unresectable colorectal cancer (CRC) randomized to treatment with nivolumab + encorafenib + cetuximab compared to encorafenib + cetuximab.

SECONDARY OBJECTIVES:

  1. To compare overall response rate (ORR), including confirmed and unconfirmed, complete and partial response, according to RECIST 1.1 criteria between the two arms.

II. To compare overall survival (OS) between the two arms. III. To compare duration of response between the two arms. IV. To compare safety and tolerability between the two arms. V. To assess immune-related PFS using modified response criteria adapted for immunotherapy (irRC-PFS) in patients treated with nivolumab + encorafenib + cetuximab.

BANKING OBJECTIVE:

  1. To bank tissue and blood specimens for future correlative studies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive encorafenib orally (PO) once daily (QD) on days 1-28, cetuximab intravenously (IV) on days 1 and 15, and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive encorafenib PO QD on days 1-28 and cetuximab IV on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed until death or 3 years after registration, whichever occurs first.

Being tested
Cetuximab, Encorafenib, Nivolumab
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms

What participants receive

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

  • CetuximabBiological

    Also called C 225, C-225, C225, Cetuxa

    Given IV

  • EncorafenibDrug

    Also called Braftovi, LGX 818, LGX-818, LGX818

    Given PO

  • NivolumabBiological

    Also called ABP 206, BCD-263, BMS 936558, BMS-936558

    Given IV

Study groups in NCT05308446
Study groupRoleWhat they receive
Arm I (encorafenib, cetuximab, nivolumab)ExperimentalPatients receive encorafenib PO QD on days 1-28, cetuximab IV on days 1 and 15, and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Cetuximab; Drug: Encorafenib; Biological: Nivolumab
Arm II (encorafenib, cetuximab)Active comparatorPatients receive encorafenib PO QD on days 1-28 and cetuximab IV on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Cetuximab; Drug: Encorafenib

What is being measured

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

  1. Progression-free survival (PFS)

    Conducted in all eligible participants according to the intent-to-treat principle using the stratified log rank test when a total of 66 PFS events have been observed. Estimated using the Kaplan-Meier method and compared using the stratified log rank test.

    Measured: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years

Secondary outcomes (5)

  1. Overall response rate (ORR)

    Evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (confirmed and unconfirmed, complete and partial response) and compared across treatment arms via Fisher's exact test.

    Measured: Up to 3 years

  2. Overall survival (OS)

    Estimated using the Kaplan-Meier method and compared using the stratified log rank test. The distribution of OS will be estimated using the method of Kaplan-Meier and compared using the stratified log rank test.

    Measured: From date of registration to date of death due to any cause, assessed up to 3 years

  3. Duration of response (DoR)

    Estimated using the Kaplan-Meier method and compared using the stratified log rank test. The distribution of DoR will be estimated using the method of Kaplan-Meier and compared using the stratified log rank test.

    Measured: From date of first documentation of confirmed response (complete response or partial response) to date of first documentation of progression or symptomatic deterioration or death due to any cause among participants who achieve a response, up to 3 years

  4. Immune related progression-free survival (irRC-PFS) in Arm I

    The distribution of irRC-PFS in Arm 1 (nivolumab + encorafenib + cetuximab) will be estimated using the method of Kaplan-Meier.

    Measured: From date of registration to date of initial documentation of irRC-progression that has subsequently been confirmed or symptomatic deterioration, or death due to any cause, assessed up to 3 years

  5. Incidence of adverse events

    At least 25 eligible participants in each arm are sufficient to estimate the probability of a particular toxicity within ±20% (95% confidence interval), and any toxicity occurring with at least 10% probability is likely (93% chance) to be seen at least once. At least 50 eligible participants are sufficient to estimate the probability of a particular toxicity within ±14% (95% confidence interval), and any toxicity occurring with at least 5% probability is likely (92% chance) to be seen at least once.

    Measured: Up to 3 years

Timeline

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

  1. First posted4 Apr 2022
  2. Study start19 Jul 2022
  3. Primary completion28 Feb 2026
  4. Study completion1 Jun 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
86 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05308446
Sponsor's protocol ID
NCI-2022-02494
Other IDs
NCI-2022-02494, S2107, S2107, U10CA180888
Status last verified
Jun 2026
First submitted
1 Apr 2022
Last updated
8 Jul 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."

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cetuximab, Encorafenib and Nivolumab in people with Metastatic Colon Adenocarcinoma and Metastatic Rectal Adenocarcinoma, run by National Cancer Institute (NCI) at 286 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 26 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 286 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?

This study is still under way. Results are not available in the source record yet.

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) (time frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years). 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 NCT05308446.

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 8 Jul 2026.

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Clinical Trial NCT05308446 | AzTrials