AzTrials
AzTrials

BRAF V600E-mutant Metastatic Colorectal CancerPhase 3BEACON CRCNCT02928224

Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer

A Phase 3 study testing Encorafenib, Binimetinib and Cetuximab in people with BRAF V600E-mutant Metastatic Colorectal Cancer, run by Pfizer at 418 sites in 27 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a multicenter, randomized, open-label, 3-arm Phase 3 study to evaluate encorafenib + cetuximab plus or minus binimetinib versus Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab, as controls, in patients with BRAFV600E mCRC whose disease has progressed after 1 or 2 prior regimens in the… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Encorafenib, Binimetinib and Cetuximab
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
702 participants
Where
418 sitesin 27 countries
Study dates
13 Oct 2016to 10 Nov 2022
Phase
Phase 3
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

  • Age ≥ 18 years at time of informed consent
  • Histologically- or cytologically-confirmed CRC that is metastatic
  • Presence of BRAFV600E in tumor tissue as previously determined by a local assay at any time prior to Screening or by the central laboratory
  • Progression of disease after 1 or 2 prior regimens in the metastatic setting
  • Evidence of measurable or evaluable non-measurable disease per RECIST, v1.1
  • Adequate bone marrow, cardiac, kidney and liver function
Show all 9Show fewer
  • Able to take oral medications
  • Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through follow-up if of childbearing potential
  • Males must agree to take appropriate precautions to avoid fathering a child from screening through follow-up

Who cannot join

  • Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab, panitumumab or other epidermal growth factor receptor (EGFR) inhibitors
  • Prior irinotecan hypersensitivity or toxicity that would suggest an inability to tolerate irinotecan 180 mg/m2 every 2 weeks
  • Symptomatic brain metastasis or leptomeningeal disease
  • History or current evidence of retinal vein occlusion or current risk factors for retinal vein occlusion (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
  • Known history of acute or chronic pancreatitis
  • History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization
Show all 16Show fewer
  • Uncontrolled blood pressure despite medical treatment
  • Impaired GI function or disease that may significantly alter the absorption of encorafenib or binimetinib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption)
  • Concurrent or previous other malignancy within 5 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy
  • History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli
  • Concurrent neuromuscular disorder that is associated with the potential of elevated creatine (phosphor)kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
  • Residual common terminology criteria for adverse events (CTCAE) ≥ Grade 2 toxicity from any prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2 neuropathy
  • Known history of HIV infection
  • Active hepatitis B or hepatitis C infection
  • Known history of Gilbert's syndrome
  • Known contraindication to receive cetuximab or irinotecan at the planned doses

Trial locations and contacts

418 sites in 27 countries.

418 sites in 27 countries

United States90 sites

  • Rocky Mountain Lions Eye Institute

    Aurora, Colorado, 80045

  • University of Colorado Cancer Center - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • University of Colorado Denver CTO (CTRC)

    Aurora, Colorado, 80045

  • University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)

    Aurora, Colorado, 80045

  • University of Colorado Hospital Inpatient Pavillion'

    Aurora, Colorado, 80045

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21287

  • The Investigational Drug Pharmacy (IDS) in the Sidney Kimmel Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21287

  • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21287

  • Memorial Sloan Kettering: Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Illinois CancerCare- Bloomington

    Bloomington, Illinois, 61704

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Ophthalmic Consultants of Boston Inc

    Boston, Massachusetts, 02114

  • Brigham & Women's Hospital

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute (DFCI)

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Gabrail Cancer Center Research

    Canton, Ohio, 44718

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Siteman Cancer Center - St Peters

    City of Saint Peters, Missouri, 63376

  • Cleveland Clinic Taussig Cancer Institute

    Cleveland, Ohio, 44195

  • Memorial Sloan Kettering: Commack

    Commack, New York, 11725

  • The Lennar Foundation Medical Center

    Coral Gables, Florida, 33146

  • Siteman Cancer Center - West County

    Creve Coeur, Missouri, 63141

  • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

    Duarte, California, 91010

  • The University of Kansas Clinical Research Center

    Fairway, Kansas, 66205

  • Broward Health Medical Center

    Fort Lauderdale, Florida, 33316

  • Dr. Clayton Berger (opthalmology)

    Fort Lauderdale, Florida, 33316

  • Mehmet F. Hepgur, MD - Broward Health Medical Center

    Fort Lauderdale, Florida, 33316

  • Compassionate Care Research Group, Inc. at Compassionate Cancer Care Medical Group, Inc.

    Fountain Valley, California, 92708

  • Illinois CancerCare- Galesburg

    Galesburg, Illinois, 61401

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030-4009

  • Indiana University Health Hospital

    Indianapolis, Indiana, 46202

  • Indiana University Health Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Investigational Drug Services IUHSCC

    Indianapolis, Indiana, 46202

  • Sidney &Lois Eskenazi Hospital

    Indianapolis, Indiana, 46202

  • IU Health Springmill

    Indianapolis, Indiana, 46290

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • The University of Kansas Hospital

    Kansas City, Kansas, 66160

  • Keck Hospital of USC - Norris Healthcare Center (HC3)

    Los Angeles, California, 90033

  • Keck Hospital of USC

    Los Angeles, California, 90033

  • LAC+USC Medical Center

    Los Angeles, California, 90033

  • Norris Healthcare Center 3 (HC3)

    Los Angeles, California, 90033

  • USC Eye Institute

    Los Angeles, California, 90033

  • USC/Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Wisconsin Clinical Science Center

    Madison, Wisconsin, 53792

  • Sylvester Comprehensive Cancer Center/UMHC

    Miami, Florida, 33136

  • Sylvester at Kendall

    Miami, Florida, 33176

  • Henry-Joyce Cancer Clinic

    Nashville, Tennessee, 37232

  • Vanderbilt Eye Institute

    Nashville, Tennessee, 37232

  • Baptist Health Floyd Cancer Center

    New Albany, Indiana, 47150

  • Smilow Cancer Hospital at Yale - New Haven

    New Haven, Connecticut, 06510

  • Temple Medical Center

    New Haven, Connecticut, 06510

  • Yale University, Yale Cancer Center

    New Haven, Connecticut, 06520

  • University of Chicago Comprehensive Cancer Center at Silver Cross Hospital

    New Lenox, Illinois, 60451

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Memorial Sloan Kettering: Rockefeller Outpatient Pavilion

    New York, New York, 10065

  • Hoag Memorial Hospital Presbyterian

    Newport Beach, California, 92663

  • Smilow Cancer Hospital Care Center at North Haven

    North Haven, Connecticut, 06473

  • Harvard Eye Associates

    Orange, California, 92868

  • The University of Chicago Medicine Center for Advanced Care Orland Park

    Orland Park, Illinois, 60462

  • Illinois CancerCare- Ottawa

    Ottawa, Illinois, 61350

  • Illinois Cancer Care, PC

    Peoria, Illinois, 61615

  • Illinois Eye Center

    Peoria, Illinois, 61615

  • Mayo Clinic Hospital

    Phoenix, Arizona, 85054

  • Mayo Clinic

    Phoenix, Arizona, 85054

  • Casey Eye Institute-South Waterfront

    Portland, Oregon, 97239

  • OHSU Center for Health and Healing

    Portland, Oregon, 97239

  • OHSU Research Pharmacy Services

    Portland, Oregon, 97239

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • KU Eye

    Prairie Village, Kansas, 66208

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Mayo Clinic

    Scottsdale, Arizona, 85259

  • Spokane Eye Clinic

    Spokane, Washington, 99204

  • Inland Imaging, LLC Holy Family Hospital

    Spokane, Washington, 99208

  • Medical Oncology Associates, PS DBA Summit Cancer Centers

    Spokane, Washington, 99208

  • Providence Holy Family Nuclear Medicine

    Spokane, Washington, 99208

  • Medical Oncology Associates, PS DBA Summit Cancer Centers

    Spokane Valley, Washington, 99216

  • SSM Health Saint Louis University Hospital

    St Louis, Missouri, 63104

  • Barnes Jewish Hospital

    St Louis, Missouri, 63110

  • Saint Louis University

    St Louis, Missouri, 63110

  • SSM Health Saint Louis University Hospital

    St Louis, Missouri, 63110

  • Washington University Infusion Center Pharmacy

    St Louis, Missouri, 63110

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center - South County

    St Louis, Missouri, 63129

  • Scott & White Clinic - Temple Pavilion

    Temple, Texas, 76504

  • Scott & White Medical Center - Temple

    Temple, Texas, 76508

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • The University of Kansas Cancer Center and Medical Pavilion

    Westwood, Kansas, 66205

  • The University of Kansas Cancer Center, Investigational Drug Services

    Westwood, Kansas, 66205

Other trials in United States

Brazil41 sites

  • Clinica Toller

    Barretos, São Paulo, 14780-110

  • Olhos Centro Diagnostico e Laser LTDA

    Barretos, São Paulo, 14780-300

  • Fundacao Pio XII

    Barretos, São Paulo, 14784-400

  • Instituto Vizibelli

    Belo Horizonte, Minas Gerais, 30110-921

  • CENANTRON - Centro Avancado de Tratamento Oncologic

    Belo Horizonte, Minas Gerais, 30130-090

  • CEMES Centro Medico Especializado em Oftalmologia

    Cachoeiro de Itapemirim, Espírito Santo, 29300-045

  • Centro de Pesquisas Clínicas em Oncologia

    Cachoeiro de Itapemirim, Espírito Santo, 29308-014

  • Hospital Evangelico de Cachoeiro de Itapemirim

    Cachoeiro de Itapemirim, Espírito Santo, 29308-055

  • Fundação Universidade de Caxias do Sul

    Caxias do Sul, Rio Grande do Sul, 95070-560

  • Giuliano Santos Borges - ME / Clinica de Neoplasias Litoral - Centro de Novos Tratamentos Itajai

    Itajaí, Santa Catarina, 88301-220

  • Daniel Lubisco Pandolfi

    Lajeado, Rio Grande do Sul, 95900-000

  • Sociedade Beneficencia e Cardade de Lajeado/Hospital Bruno Born

    Lajeado, Rio Grande do Sul, 95900-000

  • Sociedade Beneficencia e Cardade de Lajeado/Hospital Bruno Born

    Lajeado, Rio Grande do Sul, 95900-010

  • Associacao Hospitalar Beneficente Sao Vicente de Paulo / Hospital Sao Vicente de Paulo

    Passo Fundo, Rio Grande do Sul, 99010-080

  • Consultorio Medico de Oftalmologia - Dr. Ricardo Tres

    Passo Fundo, Rio Grande do Sul, 99010-080

  • Hospital Sao Vicente de Paulo

    Passo Fundo, Rio Grande do Sul, 99010-090

  • Thiago Vernetti Ferreira

    Pelotas, Rio Grande do Sul, 96010-140

  • Leandro Becker

    Pelotas, Rio Grande do Sul, 96015-280

  • Fernanda Mendes

    Pelotas, Rio Grande do Sul, 96020-080

  • UPCO - Unidade de Pesquisas Clinicas em Oncologia

    Pelotas, Rio Grande do Sul, 96020-080

  • Fernanda Lauermann

    Pelotas, Rio Grande do Sul, 96020-260

  • Diogo Duarte Torre

    Porto Alegre, Rio Grande do Sul, 90020-013

  • Farmacia Central da Irmandade da Santa Casa de Misericordia de Porto Alegre

    Porto Alegre, Rio Grande do Sul, 90020-090

  • Irmandade da Santa Casa de Misericordia de Porto Alegre

    Porto Alegre, Rio Grande do Sul, 90020-090

  • Nucleo de Novos Tratamentos em Cancer

    Porto Alegre, Rio Grande do Sul, 90050-170

  • Centro de Pesquisa Clínica de Oncologia e Hematologia - Hospital Mãe de Deus/AESC

    Porto Alegre, Rio Grande do Sul, 90110-270

  • Clinica de Oftalmologia Lavinsky

    Porto Alegre, Rio Grande do Sul, 90470-340

  • Hospital Mãe de Deus

    Porto Alegre, Rio Grande do Sul, 90880-480

  • Hospital do Olho

    Salvador, Estado de Bahia, 41820-020

  • CENOB - Centro de Oncologia da Bahia SS Ltda / Oncovida

    Salvador, Estado de Bahia, 41820-021

  • FUNDAÇÃO DO ABC - Faculdade de Medicina do ABC

    Santo André, São Paulo, 09060-650

  • FUNDAÇÃO DO ABC - Faculdade de Medicina do ABC

    Santo André, São Paulo, 09060-870

  • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto

    São José do Rio Preto, São Paulo, 15090-000

  • Instituto de Ensino e Pesquisa São Lucas

    São Paulo, 01236-030

  • Instituto de Ensino e Pesquisa São Lucas - Pharmacy

    São Paulo, 01242-020

  • Hospital Leforte

    São Paulo, 01507-000

  • IPEPO - Instituto da Visao

    São Paulo, 04038-020

  • CEPOS - Centro de Estudos e Pesquisas Oncologicas de Sorocaba

    Sorocaba, São Paulo, 18030-075

  • Instituto de Oncologia de Sorocaba "Dr. Gilson Delgado"

    Sorocaba, São Paulo, 18030-200

  • Karen Miyuki Kubokawa Shorer

    Sorocaba, São Paulo, 18040-425

  • Oftalmologia Diagnostica de Sorocaba (ODS)

    Sorocaba, São Paulo, 18047-620

Other trials in Brazil

Italy41 sites

  • Oculistica, ASST Papa Giovanni XXIII

    Bergamo, BG, 24127

  • Oncologia, ASST Papa Giovanni XXIII

    Bergamo, BG, 24127

  • Policlinico S.Orsola Malpighi, AOU di Bologna - Oncologia Medica

    Bologna, 40138

  • Divisione Anatomia Patologica Presidio San Giovanni di Dio

    Cagliari, 09124

  • Oculistica AOU di Cagliari Presidio San Giovanni di Dio

    Cagliari, 09124

  • Oculistica - ASST Cremona, Ospedale di Cremona

    Cremona, CR, 26100

  • SC Farmacia Aziendale - ASST Cremona, Ospedale di Cremona

    Cremona, CR, 26100

  • SC Oncologia - ASST Cremona, Ospedale di Cremona

    Cremona, CR, 26100

  • Dipartimento Neuromuscoloscheletrico e Organi di Senso, "Oncologia Oculare Unit"

    Florence, 50134

  • SC oncologia Medica I - Azienda Ospedaliero Universitaria Careggi

    Florence, 50134

  • IRCCS Ospedale San Raffaele - U.O. di Medicina Oncologica

    Milan, MI, 20132

  • Servizio di Farmacia - IRCCS Ospedale San Raffaele

    Milan, MI, 20132

  • S.C. Radiologia diagnostica e interventistica - Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, MI, 20133

  • SC Oncologia Medica 1, SS Oncologia Medica Gastroenterologica

    Milan, MI, 20133

  • Radiologia

    Milan, 20141

  • Unita di Oncologia Medica Gastrointestinale e Tumori Neuroendocrini

    Milan, 20141

  • Grande Ospedale Metropolitano Niguarda

    Milan, 20162

  • Dipartimento Interaziendale Farmaceutico - AOU Policlinico di Modena

    Modena, 41124

  • SC di Oftalmologia - AOU Policlinico di Modena

    Modena, 41124

  • SC di Radiologia, Dipartimento Interaziendale integrato Diagnostica per Immagini

    Modena, 41124

  • SSD Day Hospital Oncologico - Dipartimento ad attivita integrata di Oncologia, Ematologia

    Modena, 41124

  • Clinica di Oncologia Medica AOU di Cagliari Presidio Duilio Casula Monserrato

    Monserrato, Cagliari, 09042

  • Farmacia AOU di Cagliari Presidio Duilio Casula Monserrato

    Monserrato, Cagliari, 09042

  • Radiologia AOU di Cagliari Presidio Duilio Casula Monserrato

    Monserrato, Cagliari, 09042

  • AOU Universita degli Studi della Campania L. Vanvitelli - DAI di Medicina Interna e Specialistica

    Naples, 80131

  • AOU Universita degli Studi della Campania L. Vanvitelli - U. Ma.Ca.

    Naples, 80131

  • AOU Universita degli Studi della Campania L. Vanvitelli

    Naples, 80131

  • AOU Universita degli Studi della Campania L. Vanvitelli

    Naples, 80138

  • Cardiologia per i pazienti oncologici - Istituto Oncologico Veneto I.R.C.C.S

    Padova, PD, 35128

  • Clinica Oculistica - Azienda Ospedaliera di Padova

    Padova, PD, 35128

  • U.O. Oncologia Medica 1 - Istituto Oncologico Veneto I.R.C.C.S

    Padova, PD, 35128

  • UO Oculistica - AOU Pisana, Stabilimento Ospedaliero di Cisanello

    Pisa, 56124

  • SOD Radiodiagnostica 3 - AOU Pisana, Stabilimento Ospedaliero di Santa Chiara

    Pisa, 56126

  • UO Farmaceutica, Gestione del Farmaco - AOU Pisana, Stabilimento Ospedaliero di Santa Chiara

    Pisa, 56126

  • UO Oncologia Medica 2 - AOU Pisana, Stabilimento Ospedaliero di Santa Chiara

    Pisa, 56126

  • U.O.S.D. Oncologia Medica, Dipartimento di Medicina - Fondazione PTV Policlinico Tor Vergata

    Roma, 00133

  • U.O.S.D. Patologie Retiniche - Fondazione PTV Policlinico Tor Vergata

    Roma, 00133

  • U.O. Oculistica, Istituto Clinico HUMANITAS

    Rozzano, Milano, 20089

  • U.O. di Oncologia ed Ematologia, Istituto Clinico HUMANITAS

    Rozzano (MI), Milan, 20089

  • Ospedali Riuniti Umberto I

    Torrette Di Ancona, Ancona, 60020

  • ASST Bergamo Ovest, Ospedale Treviglio Caravaggio di Trevigl

    Treviglio, Bergamo, 24047

Other trials in Italy

Germany34 sites

  • Evangelisches Waldkrankenhaus Spandau

    Berlin, 13589

  • Institut f. Pathologie - Ruhr-Universitaet Bochum, Prof. Dr. med. Andrea Tannapfel

    Bochum, North Rhine Westfalia, 44789

  • Universitaetsklinikum Carl Gustav Carus der Technischen Universitaet Dresden

    Dresden, 01307

  • Kliniken Essen Mitte / Knappschaftskrankenhaus

    Essen, North Rhine-Westphalia, 35136

  • Praxis fuer Augenheilkunde Dr. Edmund Meyer-Schwickerath

    Essen, North Rhine-Westphalia, 45131

  • Kliniken Essen-Mitte

    Essen, North Rhine-Westphalia, 45136

  • Universitaetsklinikum Essen (AoeR), Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum

    Essen, North Rhine-Westphalia, 45147

  • Universitaetsklinikum Essen; Diagnostischeu. Interventionelle Radiologie u. Neuroradiologie

    Essen, North Rhine-Westphalia, 45147

  • Universitaetsklinikum Essen; Nuklearmedizin

    Essen, North Rhine-Westphalia, 45147

  • Universitaetsklinikum Essen; Zentralapotheke

    Essen, North Rhine-Westphalia, 45147

  • Evang. Krankenhaus Essen - Werden; Klinik fuer Augenheilkunde

    Essen, North Rhine-Westphalia, 45239

  • Kliniken Essen Mitte / Knappschaftskrankenhaus

    Essen, North Rhine-Westphalia, 45276

  • Augenarzt-Gemeinschaftspraxis Dr.med.Andreas Kind & Dr.med. Ute Kariger-Schweigert

    Falkensee, Brandenburg, 14612

  • Universitaetsklinikum Hamburg Eppendorf, Klinik fuer Augenheilkunde

    Hamburg, 20246

  • Facharztzentrum Eppendorf

    Hamburg, 20249

  • Universitaetsklinikum Hamburg Eppendorf, Zentrum fuer Radiologie und Endoskopie

    Hamburg, 20251

  • ZytoService Deutschland GmbH, Standort-Hamburg-Jenfeld

    Hamburg, 22045

  • HKS Kardiologische Praxis am Israelitischen Krankenhaus

    Hamburg, 22297

  • Radiologie im Israelitischen Krankenhaus

    Hamburg, 22297

  • Medizinische Hochschule Hannover (MHH)

    Hanover, Lower Saxony, 30625

  • Medizinische Hochschule Hannover

    Hanover, Lower Saxony, 30625

  • Augentagesklinik Maria-Hilf Krankenhaus

    Mönchengladbach, North Rhine-Westphalia, 41063

  • Kliniken Maria Hilf GmbH - Franziskuskrankenhaus

    Mönchengladbach, North Rhine-Westphalia, 41063

  • Kliniken Maria Hilf GmbH; Klinik fuer Radiologie

    Mönchengladbach, North Rhine-Westphalia, 41063

  • Augenklinik der Universitaet Muenchen

    Munich, Bavaria, 80336

  • LMU Klinikum der Universitaet Muenchen, Campus Grosshadern

    Munich, Bavaria, 81377

  • Lukaskrankenhaus Neuss; Zentrale Apotheke

    Neuss, North Rhine-Westphalia, 41464

  • Universitaetsklinikum Tuebingen

    Tübingen, Baden-Wurttemberg, 72076

  • Universitaetsklinikum Ulm

    Ulm, Baden-Wurttemberg, 89081

  • Augenarzt Praxis Dr. med. Petra Huelsmann

    Worms, Rhineland-Palatinate, 67547

  • Gemeinschaftspraxis fuer Radiologie und Nuklearmedizin, Standort Worms

    Worms, Rhineland-Palatinate, 67547

  • Martin Apotheke

    Worms, Rhineland-Palatinate, 67547

  • Onkologische Schwerpunktpraxis Worms

    Worms, Rhineland-Palatinate, 67547

  • Praxisgemeinschaft Kruse + Hofstaetter

    Worms, Rhineland-Palatinate, 67547

Other trials in Germany

Spain30 sites

  • Hospital del Mar

    Barcelona, 08003

  • Clinica Corachan

    Barcelona, 08017

  • Hospital Quiron Salud Barcelona

    Barcelona, 08023

  • Cetir Centre Medic S.L.

    Barcelona, 08029

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Hospital Universitario de Burgos

    Burgos, 09006

  • Hospital Universitario Reina Sofía

    Córdoba, Cordona, 14004

  • Consulta Dr. Juan Carlos Castillo Dominguez

    Córdoba, 14008

  • Complejo Hospitalario de Jaen

    Jaén, Andalusia, 23007

  • Sercosa - Clinica de las Nieves

    Jaén, Andalusia, 23007

  • Institut Catala d'Oncologia

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Hospital Nuestra Señora del Rosario

    Madrid, Madrid, Communidad Delaware, 28006

  • Gabinete Radiologico Dr. Pita

    Madrid, 28006

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28007

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034

  • Hospital Clinico San Carlos

    Madrid, 28040

  • Hospital Universitario Fundacion Jimenez Diaz

    Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital HM Universitario Sanchinarro

    Madrid, 28050

  • Hospital Universitario Son Espases

    Palma de Mallorca, Balearic Islands, 07010

  • Hospital Universitari Sant Joan de Reus

    Reus, Tarragona, 43204

  • Hospital Universitari Parc Tauli

    Sabadell, Barcelona, 08208

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

  • Clinica Oftalvist

    Valencia, 46004

  • Fundacion Instituto Valenciano de Oncologia

    Valencia, 46009

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

  • Hospital General Universitario de Valencia

    Valencia, 46014

  • Hospital Quiron Salud Zaragoza

    Zaragoza, 50006

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

France15 sites

  • Hopital Jean Minjoz

    Besançon, 25030

  • CHU Morvan

    Brest, 29609

  • Centre Ophtalmologique - Pole Vision - Clinique Val d'Ouest

    Écully, 69130

  • Centre Leon Berard

    Lyon, 69373

  • ICM Val d'Aurelle

    Montpellier, 34298

  • CHU HOTEL-Dieu

    Nantes, 44093

  • Hopital Georges Pompidou

    Paris, 75015

  • Centre hospitalier national d'ophtalmologie des Quinze-Vingts

    Paris, 75571

  • Centre Hospitalier National d'Opthalmologie des Quinze-Vingts (CHNO des XV-XX)

    Paris, 75571

  • CHU Robert Debre

    Reims, 51092

  • SCM Centre d'ophtalmologie

    Saint Jeand de Vedas, 34430

  • CHU Toulouse - Purpan, hopital Pierre-Paul Riquet

    Toulouse, 31057

  • CHU Toulouse-Institut Inuversitaire du Cancer Toulouse

    Toulouse, 31059

  • CHU Toulouse-Rangueil

    Toulouse, 31059

  • Gustave Roussy

    Villejuif, 94805

Other trials in France

Israel13 sites

  • The Barzilai Medical Center - Oncology Institute

    Ashkelon, 7830604

  • Soroka University Medical Center

    Beersheba, 8410101

  • MOR Institute

    Bnei Brak, 5126413

  • Ein-Karem Department of Medical Imaging of Hadassah Medical Organization, Hadassah Medical Center,

    Jerusalem, 9112001

  • Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem

    Jerusalem, 9112001

  • Pharmacy of Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem

    Jerusalem, 9112001

  • Mt. Scopus Department of Medical Imaging of Hadassah Medical Organization,

    Jerusalem, 91240

  • Imaging Department of Meir Medical Center

    Kfar Saba, 4428164

  • Meir Medical Center

    Kfar Saba, 4428164

  • Pharmacy of Rabin Medical Center, Beilinson Hospital

    Petah Tikva, 4941492

  • Rabin Medical Center, Beilinson Hospital

    Petah Tikva, 4941492

  • Tel Aviv Sourasky Medical Center - Oncology

    Tel Aviv, NAP, 6423906

  • The Chaim Sheba Medical Center

    Tel HaShomer, 5262100

Other trials in Israel

Japan13 sites

  • National Cancer Center Hospital

    Chuo-ku, Tokyo, 104-0045

  • National Hospital Organization Kyushu Cancer Center

    Fukuoka, 811-1395

  • Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers

    Fukuoka, 815-8588

  • Kanazawa University Hospital

    Kanazawa, Ishikawa-ken, 920-8641

  • National Cancer Center Hospital East

    Kashiwa-shi, Chiba, 277-8577

  • St. Marianna University School of Medicine Hospital

    Kawasaki, Kanagawa, 216-8511

  • Chayagasaka Eye Clinic

    Nagoya, Aichi-ken, 464-0092

  • Aichi Cancer Center Hospital

    Nagoya, Aichi-ken, 464-8681

  • National Hospital Organization Osaka National Hospital

    Osaka, 540-0006

  • Hokkaido University Hospital

    Sapporo, Hokkaido, 060-8648

  • Osaka University Hospital Laboratory for Clinical Investigation

    Suita, Osaka, 565-0871

  • Tsukahara Eye Clinic

    Yokohama, Kanagawa, 241-0821

  • Kanagawa Cancer Center

    Yokohama, Kanagawa, 241-8515

Other trials in Japan

South Korea13 sites

  • Hallym University Sacred Heart Hospital

    Anyang, Gyeonggido, 14068

  • Dong-A University Hospital

    Busan, 49201

  • Chonnam National University Hwasun Hospital

    Hwasun-gun, Jeollanam-do, 58128

  • Gachon University Gil Medical Center

    Incheon, 21565

  • Seoul National University Bundang Hospital

    Seongnam-si, Gyeonggi-do, 13620

  • Korea University Guro Hospital

    Seoul, Seoul Teugbyeolsi, 08308

  • Korea University Anam Hospital IRB

    Seoul, 02841

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital, Yonsei University Health System

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

  • The Catholic University of Korea, Seoul St. Mary's Hospital

    Seoul, 06591

  • Ajou University Hospital

    Suwon, Gyeonggi-do, 16499

Other trials in South Korea

Ukraine13 sites

  • Oftalmolohycheskyi tsentr "Vzghliad" MTs

    Dnipropetrovsk, Dnipropetrovsk Oblast, 41100

  • Oftalmolohycheskyi tsentr "Vzghliad" MTs

    Dnipropetrovsk, Dnipropetrovsk Oblast, 49027

  • Derzhavnyi zaklad, Dnipropetrovska medychna akademiia Ministerstva okhorony zdorovia Ukrainy

    Dnipropetrovsk, Dnipropetrovsk Oblast, 49102

  • Komumalnyi zaklad, Dnipropetrovska miska bahatoprofilna klinichna likarnia Nº4

    Dnipropetrovsk, Dnipropetrovsk Oblast, 49102

  • Kyivska klinichna likarnia na zaliznychnomu transporti No3 filii Tsentr okhorony zdorov'ia PAT

    Kyiv, Kyivska Oblast', 02096

  • Natsionalnyi medychnyi universytet imeni O.O Bohomltsia, kafedra onkolohii

    Kyiv, Kyivska Oblast', 02096

  • Natsionalnyi medychnyi universytet imeni O.O Bohomltsia, kafedra oftalmolohii

    Kyiv, Kyivska Oblast, 01601

  • Oleksandrivska klinichna likarnia mista Kyieva

    Kyiv, Kyivska Oblast, 01601

  • Kyivskyi miskyi klinichnyi onkotsentr

    Kyiv, Kyivska Oblast, 03115

  • DVNZ "Uzhhorodskyi natsionalnyi universytet"

    Uzhhorod, Zakarpattia Oblast, 88000

  • TOV "Zakarpatskyi Tsentr Mikrokhirurhii Oka"

    Uzhhorod, Zakarpattia Oblast, 88000

  • Tsentralna miska klinichna likarnia, Miskyi onkolohichnyi tsentr

    Uzhhorod, Zakarpattia Oblast, 88000

  • Vinnytskyi oblasnyi klinichnyi onkolohichnyi dyspanser, viddilennia khimioterapii

    Vinnytsia, Vinnytsia Oblast, 21029

Other trials in Ukraine

Czechia12 sites

  • Ocni ordinace Oftalpro s.r.o.

    Brno, 603 00

  • Masarykuv onkologicky ustav

    Brno, 656 53

  • Fakultni nemocnice Hradec Kralove

    Hradec Králové, 500 05

  • Fingerlanduv ustav patologie

    Hradec Králové, 500 05

  • I. interni kardioangiologicka klinika

    Hradec Králové, 500 05

  • Klinika nemoci koznich a pohlavnich

    Hradec Králové, 500 05

  • Nemocnicni lekarna - Usek klinickych studii

    Hradec Králové, 500 05

  • Ocni klinika

    Hradec Králové, 500 05

  • Radiologicka klinika

    Hradec Králové, 500 05

  • Fakultni nemocnice Olomouc, I. interni klinika - kardiologicka

    Olomouc, 779 00

  • Fakultni nemocnice Olomouc, Lekarna

    Olomouc, 779 00

  • Fakultni nemocnice Olomouc

    Olomouc, 779 00

Other trials in Czechia

Australia11 sites

  • Central Adelaide Local Health Network Inc. operating as Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Flinders Medical Centre

    Bedford Park, South Australia, 5042

  • Monash Health Translation Precinct - Monash Health

    Clayton, Victoria, 3168

  • St Vincent's Clinic

    Darlinghurst, NEW South Wales (nsw), 2010

  • St Vincent's Hospital Sydney

    Darlinghurst, NEW South Wales (nsw), 2010

  • Austin Health

    Heidelberg, Victoria, 3084

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

  • Marsden Eye Specialists

    Parramatta, NEW South Wales (nsw), 2150

  • Mater Misericordiae Limited

    South Brisbane, Queensland, 4101

  • Newcastle Eye Centre

    Sydney, NEW South Wales (nsw), 2300

  • Central Adelaide Local Health Network Inc. operating as The Queen Elizabeth Hospital

    Woodville South, South Australia, 5011

Other trials in Australia

Belgium11 sites

  • Imelda Ziekenhuis

    Bonheiden, 2820

  • AZ Sint-Jan Brugge - Oostende AV - Campus Sint-Jan - Oncology

    Bruges, WEST Vlaanderen, 8000

  • Grand Hopital de Charleroi (GHdC)

    Charleroi, 6000

  • UZ Antwerpen

    Edegem, 2650

  • AZ Maria Middelares

    Ghent, 9000

  • University Hospital Gasthuisberg (UZ Leuven)

    Leuven, 3000

  • Centre Hospitalier de l'Ardenne - Site de Libramont

    Libramont-Chevigny, Luxembourg, 6800

  • Centre Hospitalier Universitaire (CHU) de Liege

    Liège, 4000

  • CHC Saint Joseph

    Liège, 4000

  • AZ Delta Roeselaere-Menen

    Roeselaere, 8800

  • Centre Hospitalier Regional (CHR) - Verviers

    Verviers, 4800

Other trials in Belgium

Austria9 sites

  • DZU, Diagnose Zentrum Urania GmbH

    Vienna, 1010

  • AKH Wien

    Vienna, 1090

  • Medizinische Universitaet Wien/AKH Wien

    Vienna, 1090

  • Medizinische Universität Wien/AKH Wien

    Vienna, 1090

  • Klinikum Wels - Grieskirchen GmbH, Abteilung fuer Innere Medizin IV

    Wels, Upper Austria, 4600

  • Klinikum Wels-Grieskirchen GmbH, Abteilung fuer Augenheilkunde und Optometrie

    Wels, Upper Austria, 4600

  • Klinikum Wels-Grieskirchen GmbH, Abteilung fuer Innere Medizin II

    Wels, Upper Austria, 4600

  • Klinikum Wels-Grieskirchen GmbH, Institut fuer Nuklearmedizin

    Wels, Upper Austria, 4600

  • Klinikum Wels-Grieskirchen GmbH, Institut fuer Radiologie I

    Wels, Upper Austria, 4600

Other trials in Austria

Hungary9 sites

  • Szent Margit Kórház

    Budapest, 1032

  • Eszak-Pesti Centrumkorhaz-Honvedkorhaz

    Budapest, 1062

  • Magyar Honvedseg Egeszsegugyi Kozpont

    Budapest, 1062

  • Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet

    Budapest, 1097

  • Uzsoki Utcai Korhaz

    Budapest, 1145

  • Debreceni Egyetem Klinikai Kozpont

    Debrecen, 4032

  • Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar

    Pécs, 7624

  • Pecsi Tudomanyegyetem Klinikai Kozpont

    Pécs, 7624

  • Zala Megyei Szent Rafael Korhaz - Onkologiai Osztaly

    Zalaegerszeg, Zala County, H-8900

Other trials in Hungary

United Kingdom9 sites

  • NHS Grampian - Aberdeen Royal Infirmary

    Aberdeen, Aberdeenshire Scotland, AB25 2ZN

  • University Hospitals Birmingham NHS Foundation Trust Queen Elizabeth Hospital

    Birmingham, WEST Midlands, B15 2TH

  • Beatson West of Scotland Cancer Centre

    Glasglow, Glasglow City, Scotland, G12 0YH

  • Hammersmith Hospital, Imperial College Healthcare NHS Trust

    London, W12 0HS

  • Imperial College Healthcare NHS Trust, Hammersmith Hospital

    London, W12 0HS

  • Sarah Cannon Research Institute UK

    London, W1G 6AD

  • Imperial College Healthcare NHS Trust, Charing Cross Hospital

    London, W6 8RF

  • The Christie NHS Foundation Trust - Christie Hospital

    Manchester, M20 4BX

  • King Edward V11 Hospital

    Windsor, Berkshire, SL4 3DP

Other trials in United Kingdom

Netherlands8 sites

  • The Netherlands Cancer Institute

    Amsterdam, North Holland, 1066 CX

  • Onze Lieve Vrouwen Gasthuis

    Amsterdam, North Holland, 1091 AC

  • Rijnstate Hospital Arnhem

    Arnhem, Gelderland, 6815 AD

  • Maastricht University Medical Center (MUMC)

    Maastricht, Limburg, 6229HX

  • Haga Ziekenhuis

    The Hague, South Holland, 2545 AA

  • Universitair Medisch Centrum Utrecht

    Utrecht, 3584 CX

  • Universitair Medisch Centrum Utrecht

    Utrecht, 3584CX

  • Rijnstate Hospital Velp

    Velp, Gelderland, 6883 AZ

Other trials in Netherlands

Poland7 sites

  • Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza

    Brzozów, 36-200

  • Wojewodzki Szpital Zespolony, Oddzial Onkologiczny

    Elblag, 82-300

  • Szpital Specjalistyczny im. L. Rydygiera w Krakowie Sp.z.o.o.

    Krakow, 31-826

  • Europejskie Centrum Zdrowia Otwock, Szpital im. F. Chopina

    Otwock, 05-400

  • NZOZ Centrum Medyczne HCP

    Poznan, 61-485

  • NZOZ Przychodnia Specjalistyczna GUTMED

    Poznan, 61495

  • MAGODENT Sp. z o.o. Szpital Elblaska

    Warsaw, 01-748

Other trials in Poland

Turkey (Türkiye)7 sites

  • Hacettepe University Medical Faculty

    Ankara, 06230

  • Uludag University Hospital

    Bursa, 16059

  • Trakya Universitesi Tip Fakultesi

    Edirne, 22030

  • Medeniyet University Goztepe Training and Research Hospital

    Istanbul, Kadikoy, 34722

  • Ege University Medical Faculty

    Izmir, Bornova, 35040

  • Izmir Medical Park Hospital - Medical Oncology

    Izmir, Izmir, Karsiyaka, 35575

  • Inonu Universitesi Turgut Ozal Medical Center

    Malatya, 44280

Other trials in Turkey (Türkiye)

Canada6 sites

  • Centre integre universitaire de sante et de services sociaux de l'Ouest-de-l'Ile-de-Montreal

    Montreal, Quebec, H3T 1M5

  • The Ottawa Hospital Cancer Centre

    Ottawa, Ontario, K1H 8L6

  • Sunnybrook Research Institute

    Toronto, Ontario, M4N 3M5

  • Mount Sinai Hospital

    Toronto, Ontario, M5G 1X5

  • Eye Care Centre, Vancouver General Hospital

    Vancouver, British Columbia, V5Z 3N9

  • BC Cancer, Vancouver Center

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Russia6 sites

  • Evimed Llc

    Chelyabinsk, 454048

  • Regional Budgetary Healthcare Institution Kursk Regional Clinical

    Kursk, Kursk Oblast, 305524

  • Federal State Budget Institution "N.N. Blokhin Russian Cancer Research Center" of the

    Moscow, 115478

  • Federal State Budget Institution "N.N. Blokhin Russian Cancer Research Center"

    Moscow, 115478

  • A. Tsyb Medical Radiological Research Center - branch of the

    Obninsk, 249036

  • State Budgetary Educational Institution of Higher Professional Education First Saint Petersburg

    Saint Petersburg, 197022

Other trials in Russia

Taiwan6 sites

  • Changhua Christian Hospital

    Changhua, Changhua County, 500

  • Kaohsiung Medical University Chung-Ho Memorial Hospital

    Kaohsiung City, 807

  • China Medical University Hospital

    Taichung, 40447

  • National Cheng Kung University Hospital

    Tainan, 704

  • National Taiwan University Hospital

    Taipei, 10002

  • Chang Gung Memorial Hospital, Linkou

    Taoyuan City, 333

Other trials in Taiwan

Argentina5 sites

  • Clinica Universitaria Reina Fabiola

    Córdoba, X5004FHP

  • Centro Oncologico Riojano Integral - CORI

    La Rioja, 5300

  • CLINICA PERGAMINO S.A. (Centro de Investigacion Pergamino S.A.)

    Pergamino, Buenos Aires, 2700

  • Centro Medico CAIPO (Centro para la Atención del paciente Oncológico)

    San Miguel de Tucumán, Tucumán Province, T4000GTB

  • Centro Medico INFINITO

    Santa Rosa, La Pampa Province, L6300EAN

Other trials in Argentina

Norway4 sites

  • Colosseum Øyelegesenter C/O LB Holdings AS

    Lommedalen, 1350

  • Colosseum Øyelegesenter C/O LB Holdings AS

    Oslo, 0369

  • Oslo universitetssykehus, Radiumhospitalet

    Oslo, 0379

  • Sykehusapoteket Oslo, Radiumhospitalet

    Oslo, 0379

Other trials in Norway

Chile2 sites

  • Instituto Clinico Oncologico del Sur (ICOS)

    Temuco, Araucania, 4810469

  • Hospital Clinico Vina Del Mar

    Viña del Mar, V Region Valparaiso, 2520612

Other trials in Chile

Mexico2 sites

  • Superare Centro de Infusion S.A. de C.V.

    Delegacion Cuauhtemoc, Mexico City, 06760

  • Consultorio dentro de la Torre Medica Dalinde (Oncologia Medica)

    Mexico City, Cuauhtemoc, 06760

Other trials in Mexico

Denmark1 site

  • Odense University Hospital (OUH)

    Odense C, DK-5000

Other trials in Denmark

About this study

Official title: A Multicenter, Randomized, Open-label, 3-Arm Phase 3 Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer

This is a multicenter, randomized, open-label, 3-arm Phase 3 study to evaluate encorafenib + cetuximab plus or minus binimetinib versus Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab, as controls, in patients with BRAFV600E mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting. The study contains a Safety Lead-in Phase in which the safety and tolerability of encorafenib + binimetinib + cetuximab will be assessed prior to the Phase 3 portion of the study.

Being tested
Encorafenib, Binimetinib, Cetuximab, Irinotecan, Folinic Acid
Keywords
Colorectal cancer, BRAF, BRAFV600E
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • EncorafenibDrug

    Orally, once daily.

  • BinimetinibDrug

    Orally, twice daily.

  • CetuximabDrug

    Standard of care.

  • IrinotecanDrug

    Standard of care.

  • Folinic AcidDrug

    Also called FA

    Standard of care.

  • 5-FluorouracilDrug

    Also called 5-FU

    Standard of care.

Study groups in NCT02928224
Study groupRoleWhat they receive
Safety Lead-in, Triplet ArmExperimentalEncorafenib + binimetinib + cetuximab.
Receives: Drug: Encorafenib; Drug: Binimetinib; Drug: Cetuximab
Doublet ArmExperimentalEncorafenib + cetuximab.
Receives: Drug: Encorafenib; Drug: Cetuximab
Control ArmActive comparatorInvestigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.
Receives: Drug: Cetuximab; Drug: Irinotecan; Drug: Folinic Acid; Drug: 5-Fluorouracil

What is being measured

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

  1. (Safety Lead-in) Number of Participants With Dose-Limiting Toxicities (DLTs)

    Measured: Cycle 1 (up to 28 days)

  2. (Safety Lead-in) Number of Participants With Adverse Events (AEs)

    An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants reporting AEs were reported in this outcome measure.

    Measured: Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)

  3. (Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) - Interim Analysis

    An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants with dose interruptions, dose modifications and dose discontinuations due to AEs were reported in this outcome measure.

    Measured: Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)

  4. (Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) - Final Analysis

    An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants according to incidence of dose interruptions, dose modifications and dose discontinuations due to AEs were reported in this outcome measure.

    Measured: From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks)

  5. (Phase 3) Overall Survival (OS) of Triplet Arm vs. Control Arm - Interim Analysis

    OS was defined as the time from randomization to death due to any cause.

    Measured: From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.1 weeks for triplet arm and 52.4 weeks for control arm)

  6. (Phase 3) Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 of Triplet Arm vs. Control Arm

    ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of complete response (CR) or partial response (PR), where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 millimeter [mm] short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits.

    Measured: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

Secondary outcomes (63)

  1. (Safety Lead-in) Objective Response Rate (ORR) by Investigator

    ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits.

    Measured: From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks)

  2. (Safety Lead-in) Objective Response Rate (ORR) by BICR

    ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits.

    Measured: From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks)

  3. (Safety Lead-in) Duration of Response (DOR) by Investigator

    DOR was defined as the time from first radiographic evidence of response to the earliest documented disease progression (PD) or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From time of response to the earliest documented PD or death due to underlying disease (maximum treatment exposure of 280 weeks)

  4. (Safety Lead-in) Duration of Response (DOR) by BICR

    DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From time of response to the earliest documented PD or death due to underlying disease (maximum treatment exposure of 280 weeks)

  5. (Safety Lead-in) Time to Response by Investigator

    Time to response was defined as the time from first dose to first radiographic evidence of response.

    Measured: From first dose to first radiographic evidence of response (maximum treatment exposure of 280 weeks)

  6. (Safety Lead-in) Time to Response by BICR

    Time to response was defined as the time from first dose to first radiographic evidence of response.

    Measured: From first dose to first radiographic evidence of response (maximum treatment exposure of 280 weeks)

  7. (Safety Lead-in) Progression-Free Survival (PFS) by Investigator

    PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 280 weeks)

  8. (Safety Lead-in) Progression-Free Survival (PFS) by BICR

    PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 280 weeks)

  9. (Phase 3) Overall Survival (OS) in Doublet Arm vs. Control Arm

    OS was defined as the time from randomization to death due to any cause.

    Measured: From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.7 weeks for doublet arm and 52.4 weeks for control arm)

  10. (Phase 3) Overall Survival (OS) in Triplet Arm vs. Doublet Arm

    OS was defined as the time from randomization to death due to any cause.

    Measured: From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.7 weeks for doublet arm and 89.1 weeks for triplet arm)

  11. (Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Control Arm Per BICR

    PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)

  12. (Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Control Arm Per Investigator

    PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)

  13. (Phase 3) Comparison of Progression-Free Survival (PFS) in Doublet Arm vs Control Arm Per BICR

    PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)

  14. (Phase 3) Comparison of Progression-Free Survival (PFS) in Doublet Arm vs Control Arm Per Investigator

    PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)

  15. (Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Doublet Arm Per BICR

    PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)

  16. (Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Doublet Arm Per Investigator

    PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)

  17. (Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Control Arm Per Investigator

    ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits.

    Measured: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

  18. (Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per BICR

    ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits.

    Measured: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

  19. (Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per Investigator

    ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits.

    Measured: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

  20. (Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per BICR

    ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits.

    Measured: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

  21. (Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per Investigator

    ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits.

    Measured: Duration of Phase 3, approximately 6 months (up to 28 days per cycle)

  22. (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per BICR

    DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)

  23. (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per Investigator

    DOR was defined as the time from first radiographic evidence of response to the earliest documented disease progression (PD) or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)

  24. (Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per BICR

    DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From time of response to PD or death due to underlying disease (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)

  25. (Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per Investigator

    DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From time of response to PD or death due to underlying disease (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)

  26. (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by BICR

    DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)

  27. (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by Investigator

    DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.

    Measured: From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)

  28. (Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per BICR

    Time to response was defined as the time from first dose to first radiographic evidence of response.

    Measured: From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)

  29. (Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per Investigator

    Time to response was defined as the time from first dose to first radiographic evidence of response.

    Measured: From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)

  30. (Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per BICR

    Time to response was defined as the time from first dose to first radiographic evidence of response.

    Measured: From first dose to first radiographic evidence of response (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)

  31. (Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per Investigator

    Time to response was defined as the time from first dose to first radiographic evidence of response.

    Measured: From first dose to first radiographic evidence of response (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)

  32. (Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per BICR

    Time to response was defined as the time from first dose to first radiographic evidence of response.

    Measured: From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)

  33. (Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per Investigator

    Time to response was defined as the time from first dose to first radiographic evidence of response.

    Measured: From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)

  34. (Phase 3) Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Participants (QLQ-C30) Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet

    The EORTC QLQ-C30 questionnaire consisted of 30 questions generating 5 functional scores (physical, role, cognitive, emotional, \& social); a global health (GH) status/global quality of life scale score; 3 symptom scale scores (fatigue, pain, \& nausea \& vomiting); \& 6 standalone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, \& diarrhea) \& perceived financial burden. All items were graded by severity experienced during previous week \& used 4-point-scale (1: not at all, 2: a little, 3: quite a bit, 4: very much). The scores were converted to health-related quality of life (HRQoL) scale ranging from 0-100. Higher scores indicating higher response levels (i.e., higher functioning, higher symptom severity).

    Measured: Baseline, Cycle(C)1 Day(D)1 , C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days)

  35. (Phase 3) Change From Baseline in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet

    FACT-C= Functional Assessment of Chronic Illness Therapy (FACIT), which assessed HRQoL of cancer participants \& participants with other chronic illnesses. It consists of total 36 items (27 items of general version of FACT-C and disease-specific subscale containing 9 CRC-specific items), summarized to 5 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items); all 3 subscales range:0-28, emotional well-being (6 items) range: 0-24, colorectal cancer subscale (9 items) range: 0-36; higher subscale score= better QoL. All single-item measures range: 0= 'Not at all' to 4= 'Very much'. Table summarizes functional well-being subscale, individual questions are linearly scaled \& combined to form functional well-being subscale score (range 0-28). High score represents better QoL.

    Measured: Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days)

  36. (Phase 3) Change From Baseline in the EuroQol-5D-5L Visual Analog Scale (EQ-5D-5L VAS) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet

    The EQ-5D-5L contains 1 item for each of 5 dimensions of health-related QoL (i.e., mobility, self-care, usual activities, pain or discomfort and anxiety or depression). Response options for each item varied from having no problems to moderate problems or extreme problems. The EQ-5D-5L (v4.0) is a standardized measure of health utility that provides a single index value for one's health status. The EQ-5D-5L is frequently used for economic evaluations of health care and has been recognized as a valid and reliable instrument for this purpose. The EQ visual analog scale (VAS) is a score that is directly reported by the participant and ranges from 0 to 100 (higher is better quality health).

    Measured: Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days)

  37. (Phase 3) Change From Baseline in the Participant Global Impression of Change (PGIC) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet

    The PGIC is a measure of participant's perceptions of change in their symptoms over time that can be used as an anchoring method to determine the minimal clinically important difference for other participant reported outcome (PROs). For this assessment, participants answered the following question: "Since starting treatment, my colorectal cancer symptoms are: (1) very much improved, (2) much improved, (3) minimally improved, (4) no change, (5) minimally worse, (6) much worse or (7) very much worse."

    Measured: Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days)

  38. (Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Cetuximab

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  39. (Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Encorafenib

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  40. (Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Binimetinib

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  41. (Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve From Zero to the Last Measurable Time Point (AUClast) for Metabolite of Binimetinib (AR00426032)

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  42. (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Cetuximab

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  43. (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Encorafenib

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  44. (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Binimetinib

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  45. (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Metabolite of Binimetinib (AR00426032)

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  46. (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Cetuximab

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  47. (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Encorafenib

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  48. (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Binimetinib

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  49. (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Metabolite of Binimetinib (AR00426032)

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  50. (Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Binimetinib

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  51. (Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Encorafenib

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  52. (Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Cetuximab

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  53. (Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for a Metabolite of Binimetinib

    Measured: Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)

  54. (Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Encorafenib

    The reported cross-arm CL/F value is a fixed-effect parameter determined from a population PK analysis. The analysis included pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register.

    Measured: 2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days)

  55. (Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Binimetinib

    The reported cross-arm CL/F value is a fixed-effect parameter determined from a population PK analysis. The analysis included pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register.

    Measured: 2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days)

  56. (Phase 3) Evaluation of the Model-Based Clearance (CL) for Cetuximab

    The reported cross-arm CL/F value is a fixed-effect parameter determined from a population PK analysis. The analysis included pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register.

    Measured: 2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days)

  57. Phase 3: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters

    Clinically notable shifts was defined as worsening by at least 2 grades or to more than or equal to (>=) Grade 3 based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life threatening and Grade 5: death.

    Measured: From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)

  58. Phase 3: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters

    Clinically notable shifts was defined as worsening by at least 2 grades or to >= Grade 3 based on CTCAE version 4.03 where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life threatening and Grade 5: death.

    Measured: From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)

  59. Phase 3: Number of Participants With Clinically Notable Shifts in Urinalysis Laboratory Parameters

    Clinically notable shifts was defined as worsening by at least 2 grades or to >= Grade 3 based on CTCAE version 4.03 where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life threatening and Grade 5: death.

    Measured: From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)

  60. Phase 3: Number of Participants With Newly Occurring Clinically Notable Vital Sign Abnormalities

    Newly occurring clinically notable changes was defined as participants not meeting the criterion at baseline and meeting criterion post-baseline. The criterion included: low/high systolic blood pressure (SBP): <= 90 millimeters of mercury (mmHg) with decrease from baseline of >= 20mmHg or >= 160mmHg with increase from baseline of >= 20mmHg, low or high diastolic blood pressure (DBP): <= 50mmHg with decrease from baseline of >= 15mmHg or >= 100mmHg with increase from baseline of >= 15mmHg, low or high pulse: <= 50 beats/min with decrease from baseline of >= 15 beats/min or >= 120 beats/min with increase from baseline of >= 15 beats/min, low or high temperature: <= 36 degree Celsius (deg C) or >= 37.5 deg C.

    Measured: From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)

  61. Phase 3: Number of Participants With Newly Occurring Clinically Notable Electrocardiogram (ECG) Values

    Newly occurring clinically notable changes was defined as participants not meeting the criterion at baseline and meeting criterion post-baseline. The criterion included: heart rate- decrease from baseline > 25% and to a value < 50 and increase from baseline > 25% and to a value > 100. QT interval- new > 450 (millisecond) msec, new > 480 msec, new > 500 msec, increase from baseline > 30 msec and increase from baseline > 60 msec. QTcF- new > 450 msec, new > 480 msec, new > 500 msec, increase from baseline > 30 msec and increase from baseline > 60 msec.

    Measured: From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)

  62. Phase 3: Number of Participants With Shift in Visual Acuity Logarithm of the Minimum Angle of Resolution (LogMAR) Score

    Visual acuity was measured using the Snellen visual acuity conversion chart. This was determined by establishing the smallest optotypes that could be identified correctly by the participant at a given observation distance. Snellen visual acuity was reported as a Snellen fraction (m/M) in which the numerator (m) indicated the test distance and the denominator (M) indicated the distance at which the gap of the equivalent Landolt ring subtends 1 minute of arc. The LogMAR score was calculated as - log(m/M). The maximum increase in score of <= 0, 0 to < 0.1, 0.1 to < 0.2, 0.2 to < 0.3 and >=0.3 relative to baseline in LogMAR were reported in this endpoint.

    Measured: From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)

  63. Phase 3: Number of Participants With Shifts in Left Ventricular Ejection Fraction (LVEF) From Baseline to Maximum Grade On-treatment

    Left ventricular ejection fraction (LVEF) abnormalities were defined according to CTCAE version 4.03 where Grade 0: Non-missing value below Grade 2, Grade 2: LVEF between 40% and 50% or absolute change from baseline between -10% and < -20%, Grade 3: LVEF between 20% and 39% or absolute change from baseline <= -20%, Grade 4: LVEF lower than 20%. Categories with at least 1 non-zero data values showing any shift in Grade from baseline to 1 day after dose 1 (post-baseline) were reported. Participants whose grade category was unchanged (e.g. Grade 0 to Grade 0) were not reported.

    Measured: From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)

Timeline

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

  1. First posted10 Oct 2016 (estimated)
  2. Study start13 Oct 2016
  3. Primary completion11 Feb 2019
  4. Study completion10 Nov 2022

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
702 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02928224
Sponsor's protocol ID
ARRAY-818-302
Other IDs
BEACON CRC, 2015-005805-35, C4221009, 2015
Acronym
BEACON CRC
Status last verified
Dec 2023
First submitted
16 Aug 2016
Last updated
21 Dec 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
Individual data sharing
Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Publications

  • Kopetz S, Murphy DA, Pu J, Ciardiello F, Desai J, Van Cutsem E, Wasan HS, Yoshino T, Saffari H, Zhang X, Hamilton P, Xie T, Yaeger R, Tabernero J. Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial. Nat Med. 2024 Nov;30(11):3261-3271. doi: 10.1038/s41591-024-03235-9. Epub 2024 Sep 23.

    PubMed 39313594

  • Taieb J, Lonardi S, Desai J, Folprecht G, Gallois C, Marques EP, Khan S, Castagne C, Wasan H. Adverse Events Associated with Encorafenib Plus Cetuximab in Patients with BRAFV600E-mutant Metastatic Colorectal Cancer: An in-depth Analysis of the BEACON CRC Study. Clin Colorectal Cancer. 2023 Mar;22(1):59-66. doi: 10.1016/j.clcc.2022.12.003. Epub 2022 Dec 24.

    PubMed 36653241

  • Stintzing S, Seufferlein T, Rose C, Reichenbach F, Luftner D. Encorafenib in Combination With Cetuximab After Systemic Therapy in Patients With BRAFV600E Mutant Metastatic Colorectal Cancer: German Health Technology Assessment-Driven Analyses From the BEACON CRC Study. Clin Colorectal Cancer. 2022 Sep;21(3):244-251. doi: 10.1016/j.clcc.2022.04.002. Epub 2022 May 5.

    PubMed 35654691

  • Kopetz S, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Belani A, Zhang X, Tabernero J. Quality of life with encorafenib plus cetuximab with or without binimetinib treatment in patients with BRAF V600E-mutant metastatic colorectal cancer: patient-reported outcomes from BEACON CRC. ESMO Open. 2022 Jun;7(3):100477. doi: 10.1016/j.esmoop.2022.100477. Epub 2022 May 30.

    PubMed 35653981

  • Tabernero J, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Elez E, Gollerkeri A, Maharry K, Christy-Bittel J, Kopetz S. Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study. J Clin Oncol. 2021 Feb 1;39(4):273-284. doi: 10.1200/JCO.20.02088.

    PubMed 33503393

  • Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Tarpgaard LS, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N Engl J Med. 2019 Oct 24;381(17):1632-1643. doi: 10.1056/NEJMoa1908075. Epub 2019 Sep 30.

    PubMed 31566309

  • Van Cutsem E, Huijberts S, Grothey A, Yaeger R, Cuyle PJ, Elez E, Fakih M, Montagut C, Peeters M, Yoshino T, Wasan H, Desai J, Ciardiello F, Gollerkeri A, Christy-Bittel J, Maharry K, Sandor V, Schellens JHM, Kopetz S, Tabernero J. Binimetinib, Encorafenib, and Cetuximab Triplet Therapy for Patients With BRAF V600E-Mutant Metastatic Colorectal Cancer: Safety Lead-In Results From the Phase III BEACON Colorectal Cancer Study. J Clin Oncol. 2019 Jun 10;37(17):1460-1469. doi: 10.1200/JCO.18.02459. Epub 2019 Mar 20.

    PubMed 30892987

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Encorafenib, Binimetinib and Cetuximab in people with BRAF V600E-mutant Metastatic Colorectal Cancer, run by Pfizer at 418 sites in 27 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 9 inclusion and 16 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: finished, as of the sponsor's last update on 21 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 418 sites in United States, Brazil, Italy, Germany, Spain and 22 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 14 Jul 2020). 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?

(Safety Lead-in) Number of Participants With Dose-Limiting Toxicities (DLTs) (time frame: Cycle 1 (up to 28 days)). The study lists 6 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 NCT02928224, which also lists 7 linked publications.

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 21 Dec 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in