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A Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer

RecruitingPhase 3

A Randomized, Open-label Phase 3 Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
Inclusion Criteria:

* Have histologically or cytologically confirmed adenocarcinoma of the left-sided colorectal cancer. Participants must have unresectable or metastatic disease
* Determined to have Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (WT) tumor by local and/or central testing (if available)
* Must agree to the submission of fresh tumor tissue
* Have measurable disease according to RECIST v1.1
* Has not received any prior systemic therapy for unresectable or metastatic colorectal cancer (CRC). Prior adjuvant/neoadjuvant therapy in the non-metastatic disease is permitted. However, the last course of adjuvant or neoadjuvant chemotherapy must have concluded greater than (\>) 12 months prior to CRC recurrence/metastases
* Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1

Exclusion Criteria:

* Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
* Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: (a) amivantamab or cetuximab, (b) any component of mFOLFOX6 and, (c) any component of FOLFIRI
* Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
* Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status and human epidermal growth factor receptor 2 (HER2)-positive/amplified tumor
* Has prior exposure to any agents that target epidermal growth factor receptor (EGFR), mesenchymal epithelial transition (MET) or vascular endothelial growth factor (VEGF)

About the study

The purpose of this study is to compare how long the participants are disease-free (progression-free survival) when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, oxaliplatin (mFOLFOX6) or 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus cetuximab and mFOLFOX6 or FOLFIRI in adult participants with Kirsten rat sarcoma viral oncogene homolog (KRAS)/ Neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) wild type (WT) unresectable or metastatic left-sided colorectal cancer.

What is being tested

Sponsor: Janssen Research & Development, LLC · Participants: 1,000 · Started: Oct 18, 2024

Contact the study team

Official record on ClinicalTrials.gov — NCT06662786

Locations in the U.S.

ArizonaBanner MD Anderson Cancer Center, Gilbert
ArkansasSt. Bernard's Medical Center, Jonesboro
Highlands Oncology Group, Springdale
CaliforniaCBCC Global Research, Bakersfield
Los Angeles Cancer Network, Glendale
Cancer and Blood Specialty Clinic, Los Alamitos
USC Norris Comprehensive Cancer Center, Los Angeles
UCLA, Santa Monica
Providence Medical Foundation, Santa Rosa
Torrance Memorial Physicians Network, Torrance
ColoradoRocky Mountain Cancer Centers, Denver
ConnecticutYale University School Of Medicine, New Haven
District of ColumbiaGeorgetown Univ Medical Center Lombardi Cancer Center, Washington D.C.
FloridaFlorida Cancer Specialists South, Fort Myers
AdventHealth Medical Group Oncology and Hematology at Orlando, Orlando
Florida Cancer Specialists North Region, St. Petersburg
Florida Cancer Specialists East, West Palm Beach
GeorgiaGrady Memorial Hospital, Atlanta
Winship Cancer Institute Emory University, Atlanta
IllinoisIllinois Cancer Specialists, Arlington Heights
Illinois CancerCare, Peoria
IndianaFort Wayne Medical Oncology & Hematology, Fort Wayne
IowaUniversity of Iowa Hospital, Iowa City
Mission Cancer Blood, Waukee
KansasCancer Center of Kansas, Wichita
LouisianaOchsner Clinic Foundation, New Orleans
MarylandMedStar Franklin Square Medical Center, Baltimore
Frederick Health Hospital - James M Stockman Cancer Institute, Frederick
MichiganUniversity of Michigan, Ann Arbor
VA Ann Arbor Healthcare System, Ann Arbor
Henry Ford Hospital, Detroit
Start Midwest, Grand Rapids
MississippiHattiesburg Clinic, Hattiesburg
MissouriWashington University School Of Medicine, St Louis
NebraskaNebraska Cancer Specialists Midwest Cancer Center, Omaha
NevadaComprehensive Cancer Centers of Nevada, Las Vegas
New JerseyAstera Cancer Care, East Brunswick
Rutgers Cancer Institute, New Brunswick
New MexicoUniversity of New Mexico Cancer Center, Albuquerque
New YorkPerlmutter Cancer Center at NYU Long Island, Mineola
Herbert Irving Comprehensive Cancer Center Columbia University Medical Center, New York
Mount Sinai, New York
Mount Sinai West, New York
NYU Langone Medical Center NYU Hematology Associates, New York
New York Cancer and Blood Specialists, Shirley
Montefiore Einstein Comprehensive Cancer Center, The Bronx
University of Buffalo Kaleida Health Cancer Care, Williamsville
North CarolinaUniversity of North Carolina at Chapel Hill, Chapel Hill
OhioGabrail Cancer Center, Canton
Cleveland Clinic Cancer Center Fairview Hospital Moll Pavilion, Cleveland
Taussig Cancer Insititute Cleveland Clinic, Cleveland
University Hospitals Cleveland Medical Center, Cleveland
Cleveland Clinic Cancer Center Independence Family Health Center, Independence
Cleveland Clinic Cancer Center Mansfield, Mansfield
Cleveland Clinic Cancer Center Hillcrest Hospital, Mayfield Heights
Cleveland Clinic Cancer Centers Sandusky, Sandusky
Cleveland Clinic Cancer Center Strongsville, Strongsville
Cleveland Clinic Cancer Center South Pointe Hospital, Warrensville Heights
Wooster Milltown Specialty and Surgery Center, Wooster
OregonSt Charles Medical Center, Bend
Oregon Health And Science University, Portland
PennsylvaniaFox Chase Cancer Center, Philadelphia
Thomas Jefferson University, Philadelphia
University Of Pittsburgh Medical Center UPMC Hillman Cancer Center, Pittsburgh
TennesseeSCRI Oncology Partners, Nashville
TexasTexas Oncology West Texas, Abilene
Texas Oncology DFW, Dallas
UT Southwestern, Dallas
MD Anderson Cancer Center, Houston
Baylor Scott and White Health 1, Round Rock
Texas Oncology - San Antonio, San Antonio
Baylor Scott and White Health, Temple
VirginiaVirginia Cancer Specialists, Arlington
Inova Schar Cancer Institute Dept of Fairfax Hospital, Fairfax
Richmond VA Medical Center, Richmond
VCU Massey Comprehensive Cancer Center, Richmond
WashingtonSwedish Cancer Institute Edmonds, Edmonds
Swedish Cancer Institute Issaquah, Issaquah
Fred Hutchinson Cancer Research Center, Seattle
Swedish Cancer Institute, Seattle
WisconsinWilliam S. Middleton Memorial VA, Madison

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.