AzTrials
AzTrials

Colorectal CancerPhase 2MODULNCT02291289

A Study of Biomarker-Driven Therapy in Metastatic Colorectal Cancer (mCRC)

A Phase 2 study testing Cetuximab, FOLFOX induction regimen and Fluoropyrimidine (5-FU/LV or capecitabine) in people with Colorectal Cancer, run by Hoffmann-La Roche at 154 sites in 23 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 randomized, multi-center, active-controlled, open-label, parallel-group study will investigate the efficacy and safety of biomarker-driven maintenance treatment for first-line mCRC. Participants with mCRC are eligible for entry and cannot have received any prior chemotherapy in the metastatic setting. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
Cetuximab, FOLFOX induction regimen and Fluoropyrimidine (5-FU/LV or capecitabine)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,044 participants
Where
154 sitesin 23 countries
Study dates
17 Apr 2015to 24 Mar 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

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

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

Who may be able to join

  • ECOG PS of less than or equal to (<=) 2
  • At least 16 weeks of life expectancy at time of entry into the study
  • Histologically confirmed colorectal cancer (CRC) with mCRC confirmed radiologically
  • Measureable, unresectable disease according to RECIST 1.1
  • No prior chemotherapy for CRC in the metastatic setting
  • Archival tumor formalin-fixed paraffin-embedded tissue block from the primary tumor obtained at the time of the initial diagnosis is available
  • Adequate hematological, liver and renal function
  • Agreement to use highly effective measures of contraception

Who cannot join

  • Less than 6 months from completion of any prior neoadjuvant or adjuvant chemotherapy, radiotherapy
  • Prior or current treatment with bevacizumab or any other anti-angiogenic drug (vascular endothelial growth factor or vascular endothelial growth factor receptor therapies or tyrosine kinase inhibitors)
  • Current or recent (within 10 days of study enrollment) use of aspirin (more than [>] 325 milligrams per day [mg/day]), clopidogrel (> 75 mg/day), or current or recent (within 10 days prior to the start of study induction treatment) use of therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (prophylactic uses allowed)
  • Active infection requiring intravenous antibiotics at the start of study induction treatment
  • Previous or concurrent malignancy, except for adequately treated basal or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the participant has been disease-free for 5 years prior to study entry
  • Inadequately controlled hypertension; prior history of hypertensive crisis or hypertensive encephalopathy
Show all 65Show fewer
  • Clinically significant (active) cardiovascular disease, for example cerebrovascular accidents <= 6 months prior to start of study induction treatment, myocardial infarction <= 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Functional Classification Grade II or greater congestive heart failure, or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment
  • Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of start of study induction treatment
  • Active symptomatic or untreated central nervous system (CNS) metastases; CNS disease other than supratentorial or cerebellar metastases (in other words, patients with metastases to midbrain, pons, medulla or spinal cord are excluded); history of or known carcinomatous meningitis
  • Known hypersensitivity to any component of any of the study induction or maintenance treatment medications
  • Pregnancy or lactation
  • Inability to swallow pills
  • Refractory nausea and vomiting, malabsorption, external biliary shunt or significant bowel resection that would preclude adequate absorption
  • History or presence of clinically significant ventricular or atrial dysrhythmias
  • Corrected QT (QTc) interval >= 450 millisecond assessed within 3 weeks prior to randomization, long QT syndrome or, uncorrectable electrolyte abnormalities (including magnesium) or requirement for medicinal products known to prolong the QT interval
  • ECOG PS > 2
  • History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
  • Prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis at most recent chest imaging (computed tomography [CT] scan or magnetic resonance imaging [MRI])
  • Positive test for human immunodeficiency virus (HIV)
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) at Screening
  • Active tuberculosis
  • Severe infection within 4 weeks prior to start of maintenance treatment including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia; has signs or symptoms of significant infection or has received oral or IV antibiotics within 2 weeks prior to start of maintenance treatment
  • Administration of a live, attenuated vaccine within 4 weeks prior to start of maintenance treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study
  • Prior treatment with cluster of differentiation (CD) 137 agonists, anti-cytotoxic T-lymphocyte-associated antigen (CTLA) 4, anti-programmed death-1 (PD-1), or anti-programmed death-ligand 1 (PD-L1) therapeutic antibody or pathway-targeting agents
  • Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to start of maintenance treatment
  • Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to start of maintenance treatment, or anticipated requirement for systemic immunosuppressive medications during the remainder of the study
  • If receiving receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor (for example, denosumab) and unwilling to adopt alternative treatment such as bisphosphonates while receiving atezolizumab
  • Inability to swallow pills
  • Left ventricular ejection fraction (LVEF) less than (<) 50 percent (%) as assessed after completion of induction treatment by either 2-dimensional echocardiogram or multiple-gated acquisition
  • Clinically significant cardiovascular disease, including unstable angina, history of or active congestive heart failure of ≥ NYHA Grade 2, history of or ongoing serious cardiac arrhythmia requiring treatment (except for controlled atrial fibrillation and/or paroxysmal supraventricular tachycardia).
  • Current uncontrolled hypertension with or without medication
  • Current dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy
  • Insulin-dependent diabetes
  • Current known infection with HIV, HBV, or HCV (active infection or carriers)
  • Requirement for concurrent use of the antiviral agent sorivudine (antiviral) or chemically related analogues, such as brivudine
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis
  • Known hypersensitivity to murine proteins
  • Inability to swallow medications
  • History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on most recent chest imaging (CT scan or MRI)
  • Malabsorption condition that would alter the absorption of orally administered medications
  • Amylase or lipase ≥ 1.5 times the upper limit of normal within 14 days prior to maintenance treatment initiation
  • Serum albumin less than (<) 2.5 grams per deciliter (g/dL)
  • LVEF < institutional lower limit of normal or < 50%, whichever is lower
  • Poorly controlled hypertension
  • Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters are allowed
  • Unstable angina, new onset angina within last 3 months, myocardial infarction within last 6 months and current congestive heart failure ≥ NYHA Grade 2
  • History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to initiation of maintenance treatment
  • History or evidence of intracranial hemorrhage or spinal cord hemorrhage
  • Evidence of clinically significant vasogenic edema
  • Any hemorrhage or bleeding event ≥ National Cancer Institute Common Terminology Criteria for Adverse Events Grade 3 within 28 days prior to initiation of maintenance treatment
  • History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for central serous retinopathy, retinal vein occlusion, or neovascular macular degeneration
  • Positive HIV test
  • Active HBV or HCV
  • Active tuberculosis
  • Severe infection within 4 weeks prior to start of maintenance treatment including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia; has signs or symptoms of significant infection or has received oral or IV antibiotics within 2 weeks prior to start of maintenance treatment.
  • Prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • Administration of a live, attenuated vaccine within 4 weeks prior to start of study maintenance treatment or anticipation that such a live attenuated vaccine will be required during the study
  • Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
  • Prior treatment with a mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) or ERK inhibitor
  • Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to start of study maintenance treatment
  • Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to start of study maintenance treatment, or requirement for systemic immunosuppressive medications during the trial.
  • If receiving a RANKL inhibitor (for example, denosumab), unwilling to adopt alternative treatment such as (but not limited to) bisphosphonates, while receiving atezolizumab.
  • Consumption of foods, supplements or drugs that are potent cytochrome P450 3A4 (CYP3A4) enzyme inducers or inhibitors ≤ 7 days before initiation of study maintenance treatment or expected concomitant use during maintenance treatment. These include St. John's wort or hyperforin (potent CYP3A4 enzyme inducer) and grapefruit juice (potent CYP3A4 enzyme inhibitor)

Trial locations and contacts

154 sites in 23 countries.

154 sites in 23 countries

Germany27 sites

  • Hämatologie Onkologie im Zentrum MVZ GmbH

    Augsburg, 86150

  • Onkologische Schwerpunktpraxis Kurfürstendamm

    Berlin, 10707

  • DRK Kliniken Berlin Köpenick Darmzentrum

    Berlin, 12559

  • BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie

    Dresden, 01307

  • Krankenhaus Nordwest; Klinik f. Onkologie und Hämatologie

    Frankfurt, 60488

  • PIOH PD Dr. R. Schnell ? Dr. H. Schulz ? Dr. M. Hellmann

    Frechen, 50226

  • Klinik Fulda, Medizinisches Versorgungszentrum Osthessen GmbH

    Fulda, 36043

  • Universitätsklinikum Hamburg-Eppendorf, Onkologisches Zentrum, Studienzentrale der II. Med. Klinik

    Hamburg, 20246

  • Medizinische Hochschule Hannover; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie

    Hanover, 30625

  • SLK-Kliniken Heilbronn GmbH; Klinik für Innere Medizin III; Schwerpunkt Häma./Onko./Palliativm.

    Heilbronn, 74078

  • Klinik der Ruhr-Uni Bochum; Marien-Hospital Herne

    Herne, 44625

  • Gemeinschaftspraxis für Hämatologie und Onkologie, PD Dr. Bauer, Dr. Thiel

    Lebach, 66822

  • Onkologische Gemeinschaftspraxis

    Magdeburg, 39104

  • Klinikum Magdeburg gGmbH Klinik für Allgemein- und Viszeralchirurgie

    Magdeburg, 39130

  • Universitätsklinikum Magdeburg Klinik für Gastroenterologie und Hepatologie

    Mageburg, 39120

  • Kliniken Maria Hilf GmbH, Krankenhaus St. Franziskus

    Mönchengladbach, 41063

  • Städt. Klinikum München GmbH Klinikum Neuperlach Klinik f.Hämatologie u.Onkologie

    München, 81737

  • Gemeinschaftspraxis für Hämatologie und Onkologie

    Münster, 48153

  • Brüderkrankenhaus St. Josef

    Paderborn, 33098

  • Studienzentrum Onkologie Ravensburg GbR; Onkologie Ravensburg

    Ravensburg, 88212

  • Prosper-Hospital, Medizinische Klinik I

    Recklinghausen, 45659

  • Krankenhaus Barmherziger Brüder; Klinik für Internistische Onkologie / Hämatologie

    Regensburg, 93049

  • Klinikum am Steinenberg / Ermstalklinik

    Reutlingen, 72764

  • Praxis für Hämatologie & Onkologie

    Saarbrücken, 66113

  • MVZ für Hämatologie, Onkologie, Strahlentherapie und Palliativmedizin -; Klinik Dr. Hancken

    Stade, 21680

  • Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie

    Trier, 54290

  • Klinikum Wetzlar-Braunfels, Klinik für Hämatologie/Onkologie und Palliativmedizin

    Wetzlar, 35578

Other trials in Germany

Spain26 sites

  • Hospital General Univ. de Alicante; Servicio de Oncologia

    Alicante, 3010

  • Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia

    Badalona, Barcelona, 08916

  • Hospital Universitario Reina Sofia; Servicio de Oncologia

    Córdoba, Cordoba, 14004

  • Hospital de Donostia; Servicio de Oncologia Medica

    Donostia / San Sebastian, Guipuzcoa, 20080

  • Hospital General Universitario de Elche; Servicio de Oncologia

    Elche, Alicante, 03203

  • Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia

    Jaén, 23007

  • Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia

    Lleida, 25198

  • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

    Madrid, 28007

  • Hospital Ramon y Cajal; Servicio de Oncologia

    Madrid, 28034

  • Hospital Universitario 12 de Octubre; Servicio de Oncologia

    Madrid, 28041

  • Hospital Universitario La Paz; Servicio de Oncologia

    Madrid, 28046

  • Hospital Universitario Puerta de Hierro; Servicio de Oncologia

    Majadahonda, Madrid, 28222

  • Hospital Regional Universitario Carlos Haya; Servicio de Oncologia

    Málaga, 29011

  • Hospital de Navarra; Servicio de Oncologia

    Navarra, Navarre, 31008

  • Complejo Hospitalario de Orense; Servicio de Oncologia

    Ourense, 32005

  • Hospital Univ. Central de Asturias; Servicio de Oncologia

    Oviedo, Principality of Asturias, 33011

  • Hospital Universitario Son Espases

    Palma de Mallorca, Balearic Islands, 07014

  • Hospital Univ Vall d'Hebron; Servicio de Oncologia

    Sant Andreu de la Barca, Barcelona, 08740

  • Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Oncologia

    Santa Cruz de Tenerife, Tenerife, 38010

  • Hospital Universitario Marques de Valdecilla; Servicio de Oncologia

    Santander, Cantabria, 39008

  • Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia

    Santiago de Compostela, LA Coruña, 15706

  • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

    Valencia, 46010

  • Hospital General Universitario de Valencia; Servicio de oncologia

    Valencia, 46014

  • Hospital Universitario la Fe; Servicio de Oncologia

    Valencia, 46026

  • Hospital Clinico Universitario Lozano Blesa; Servicio de Oncologia

    Zaragoza, 50009

  • Hospital Universitario Miguel Servet; Servicio Oncologia

    Zaragoza, 50009

Other trials in Spain

France14 sites

  • Clinique Sainte Catherine

    Avignon, 84082

  • HOPITAL JEAN MINJOZ; Oncologie

    Besançon, 25030

  • Hopital Augustin Morvan; Federation De Cancerologie

    Brest, 29200

  • Chu Estaing; Chir Generale Digestive A Et B

    Clermont-Ferrand, 63003

  • Hôpital Franco-Britannique- Fondation Cognacq-Jay; Cancerologie

    Levallois-Perret, 92300

  • Hopital Claude Huriez; Medecine Interne Oncologie

    Lille, 59037

  • Ch De Montbeliard;Chir Generale Digestive

    Montbéliard, 25209

  • Hopital Caremeau; Gastro Enterologie

    Nîmes, 30029

  • Hopital Saint Antoine; Oncologie Medicale

    Paris, 75571

  • Hopital Haut Leveque

    Pessac, 33600

  • Chu La Miletrie; Gastro Enterologie Endoscopies

    Poitiers, 86021

  • ICANS

    Strasbourg, 67200

  • Hopital Rangueil; Gastro Enterologie Et Nutrition

    Toulouse, 31059

  • Institut Gustave Roussy; Departement Oncologie Medicale

    Villejuif, 94805

Other trials in France

Italy13 sites

  • Humanitas Gavazzeni;U.O. Oncologia Medica

    Bergamo, Lombardy, 24121

  • Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1

    Florence, Tuscany, 50139

  • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica

    Meldola, Emilia-Romagna, 47014

  • Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1

    Milan, Lombardy, 20133

  • Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica

    Milan, Lombardy, 20141

  • Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

    Milan, Lombardy, 20162

  • IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A

    Naples, Campania, 80131

  • IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima

    Padova, Veneto, 35128

  • A.O. Universitaria Di Parma; Oncologia Medica

    Parma, Emilia-Romagna, 43100

  • Istituto Regina Elena; Oncologia Medica A

    Rome, Lazio, 00168

  • Policlinico Universitario "Agostino Gemelli"; U.O.C. Oncologia Medica

    Rome, Lazio, 00168

  • IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia

    San Giovanni Rotondo, Apulia, 71013

  • A.O.U.I. VERONA-OSPEDALE POLICLINICO G.B. ROSSI BORGO ROMA;ONCOLOGIA MEDICA-d.U.

    Verona, Veneto, 37134

Other trials in Italy

United Kingdom11 sites

  • Aberdeen Royal Infirmary; Medical Oncology Dept

    Aberdeen, AB25 2ZN

  • Birmingham Heartlands Hospital

    Birmingham, B9 5SS

  • Broomfield Hospital; Oncology

    Chelsmford, CM1 7ET

  • Castle Hill Hospital; The Queens Centre for Oncology and Haematology

    Cottingham, HU16 5JG

  • Guys and St Thomas NHS Foundation Trust, Guys Hospital

    London, SE1 9RT

  • Royal Marsden Hospital; Dept of Med-Onc

    London, SW3 6JJ

  • Christie Hospital Nhs Trust; Medical Oncology

    Manchester, M2O 4BX

  • Mount Vernon Hospital

    Middlesex, HA6 2RN

  • Queen's Hospital

    Romford, RM7 0AG

  • Southampton General Hospital; Medical Oncology

    Southampton, SO16 6YD

  • Royal Marsden Hospital; Dept. of Medicine

    Sutton, SM2 5PT

Other trials in United Kingdom

Brazil7 sites

  • Hospital de Cancer de Barretos

    Barretos, São Paulo, 14784-400

  • Hospital Amaral Carvalho

    Jaú, São Paulo, 17210-120

  • Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia

    Passo Fundo, Rio Grande do Sul, 99010-260

  • Hospital das Clinicas - UFRGS

    Porto Alegre, Rio Grande do Sul, 90035-903

  • Hospital Nossa Senhora da Conceicao

    Porto Alegre, Rio Grande do Sul, 91350-200

  • Faculdade de Medicina de Sao Jose do Rio Preto - FAMERP*X*

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

  • Instituto de Ensino e Pesquisa Sao Lucas - IEP

    São Paulo, São Paulo, 01236-030

Other trials in Brazil

Greece7 sites

  • Agioi Anargyroi; 3Rd Dept. of Medical Oncology

    Athens, 145 64

  • Univ General Hosp Heraklion; Medical Oncology

    Heraklion, 711 10

  • Uni Hospital of Ioannina; Oncology Dept.

    Ioannina, 455 00

  • University Hospital of Patras Medical Oncology

    Pátrai, 265 04

  • Thermi Clinic; Oncology Clinic

    Thermi Thessalonikis, 570 01

  • Bioclinic Thessaloniki

    Thessaloniki, 546 22

  • Euromedical General Clinic of Thessaloniki; Oncology Department

    Thessaloniki, 546 45

Other trials in Greece

Netherlands7 sites

  • Antoni van Leeuwenhoek Ziekenhuis

    Amsterdam, 1066 CX

  • Ijsselland Ziekenhuis; Inwendige Geneeskunde

    Capelle aan den IJssel, NL 2900 AR

  • Deventer Ziekenhuis; Interne Geneeskunde

    Deventer, 7416 SE

  • Albert Schweitzer Ziekenhuis - loc Dordrecht

    Dordrecht, 3318 AT

  • Catharina ZKHS; Inwendige Geneeskunde Afd.

    Eindhoven, 5623 EJ

  • St. Antonius locatie Leidsche Rijn

    Utrecht, 3543 AZ

  • Isala Klinieken

    Zwolle, 8011 JW

Other trials in Netherlands

Turkey (Türkiye)6 sites

  • Acibadem University School of Medicine, Adana Hospital; General Surgery

    Adana, 01130

  • Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department

    Edirne, 22770

  • Istanbul Uni Capa Medical Faculty; Inst. of Oncology

    Istanbul, 34093

  • Marmara Uni Faculty of Medicine; Medical Oncology

    Istanbul, 34890

  • Ege Uni Medical Faculty Hospital; Oncology Dept

    Izmir, 35100

  • Hacettepe Uni Medical Faculty Hospital; Oncology Dept

    Sihhiye/Ankara, 06230

Other trials in Turkey (Türkiye)

Belgium5 sites

  • Institut Jules Bordet X

    Brussels, 1000

  • Hospital Erasme

    Brussels, 1070

  • UZ Leuven Gasthuisberg

    Leuven, 3000

  • CHC MontLégia

    Liège, 4000

  • AZ Delta (Campus Rumbeke)

    Roeselare, 8800

Other trials in Belgium

Denmark5 sites

  • Herlev Hospital; Afdeling for Kræftbehandling

    Herlev, 2730

  • Regionshospitalet Gødstrup; Kræftafdelingen

    Herning, 7400

  • Rigshospitalet; Onkologisk Klinik

    København Ø, 2100

  • Odense Universitetshospital, Onkologisk Afdeling R

    Odense C, 5000

  • Sygehus Syd Roskilde; Onkologisk/haematologisk ambulatorium

    Roskilde, 4000

Other trials in Denmark

Mexico4 sites

  • Fundacion Rodolfo Padilla Padilla A.C.

    León, Guanajuato, 37000

  • Instituto Nacional de Cancerologia; Oncology

    Mexico City, 14080

  • Oaxaca Site Management Organization

    Oaxaca City, Oaxaca, 68000

  • Cancerologia de Queretaro; Oncologia

    Queretaro, Queretaro, Querétaro, 76090

Other trials in Mexico

South Korea4 sites

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital, Yonsei University Health System

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

Argentina3 sites

  • Hospital de Gastroenterologia Dr. Bonorino Udaondo ; Servicio de Oncología

    Buenos Aires, C1264AAA

  • Centro Oncologico Riojano Integral (CORI)

    La Rioja, F5300COE

  • Clínica Viedma

    Viedma Rio Negro, R8500ACE

Other trials in Argentina

Egypt2 sites

  • National Cancer Institute

    Cairo, 11796

  • Ain Shams University Hospital; Oncology

    Cairo

Other trials in Egypt

Poland2 sites

  • Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii

    Krakow, 30-688

  • Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Klinika Onkologii i Radioterapii,

    Warsaw, 02-781

Other trials in Poland

Portugal2 sites

  • HUC; Servico de Oncologia Medica

    Coimbra, 3000-075

  • Hospital de Santa Maria; Servico de Oncologia Medica

    Lisbon, 1649-035

Other trials in Portugal

Russia2 sites

  • Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy

    Moscow, Moscow Oblast, 115478

  • Bashkirian Republican Clinical Oncology Dispensary

    Ufa, Bashkortostan Republic, 450054

Other trials in Russia

Slovakia2 sites

  • Narodny Onkologicky Ustav; Oddelenie klinickej onkologie E

    Bratislava, 833 10

  • POKO Poprad; Department of Oncology

    Poprad, 058 01

Other trials in Slovakia

Sweden2 sites

  • Skånes University Hospital, Skånes Department of Onclology

    Lund, 221 85

  • Karolinska Hospital; Oncology - Radiumhemmet

    Stockholm, 171 76

Other trials in Sweden

Bosnia and Herzegovina1 site

  • University Clinical Center of the Republic of Srpska

    Banja Luka, 78000

Other trials in Bosnia and Herzegovina

Serbia1 site

  • Institute for Oncology and Radiology of Serbia; Clinic for Medical Oncology

    Belgrade, 11000

Other trials in Serbia

Slovenia1 site

  • Institute of Oncology Ljubljana

    Ljubljana, 1000

Other trials in Slovenia

About this study

Official title: A Multi-Centre Randomised Clinical Trial of Biomarker-Driven Maintenance Treatment for First-Line Metastatic Colorectal Cancer (MODUL)

This randomized, multi-center, active-controlled, open-label, parallel-group study will investigate the efficacy and safety of biomarker-driven maintenance treatment for first-line mCRC. Participants with mCRC are eligible for entry and cannot have received any prior chemotherapy in the metastatic setting. The entire study duration is anticipated to be approximately 7.5 years.

Being tested
Cetuximab, FOLFOX induction regimen, Fluoropyrimidine (5-FU/LV or capecitabine), Atezolizumab, Vemurafenib
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • CetuximabDrug

    500 mg/m^2 via IV infusion on Day 1 of every 2-week cycle

  • FOLFOX induction regimenDrug

    Administered per the Investigator's discretion in accordance with locally approved prescribing information.

  • Fluoropyrimidine (5-FU/LV or capecitabine)Drug

    Per Investigator's discretion: 5-FU 1600-2400 mg/m^2 administered via 46-hour IV infusion on Day 1 of every 2-week cycle and LV 400 mg/m^2 administered via a 2-hour infusion on Day 1 every 2 weeks or 1000 mg/m^2 twice-daily capecitabine (BID) by mouth given days 1-14 every 2 weeks. The chosen fluoropyrimidine should be administered in accordance with local prescribing information.

  • AtezolizumabDrug

    Also called MPDL3280A, RO5541267

    800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle, or a fixed dose of 840 mg

  • VemurafenibDrug

    Also called RO5185426

    960 mg vermurafenib BID by mouth

  • BevacizumabDrug

    Also called RO4876646

    5 mg/kg bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle per local prescribing information

  • TrastuzumabDrug

    Also called RO0452317

    Initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses by IV infusion on Day 1 of every 3-week treatment cycle

  • PertuzumabDrug

    Also called RO4368451

    Initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses by IV infusion on Day 1 of each 3-week treatment cycle

  • CobimetinibDrug

    Also called RO5514041

    60 mg orally once daily for 3 weeks followed by a 1-week treatment break

  • 5-FU/LVDrug

    1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle until disease progression per the Investigator's assessment using modified Response Evaluation Criteria in Solid Tumors or death from any cause, whichever occurs first. The fluoropyrimidine should be administered in accordance with local prescribing information.

  • CapecitabineDrug

    1000 mg/m^2 twice-daily capecitabine (BID) by mouth given days 1-14 every 2 weeks. The fluoropyrimidine should be administered in accordance with local prescribing information.

Study groups in NCT02291289
Study groupRoleWhat they receive
Cohort 1: Induction Phase (IP)OtherIncludes participants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
Receives: Drug: FOLFOX induction regimen; Drug: Bevacizumab; Drug: 5-FU/LV
Cohort 2 (IP)OtherIncludes participants with BRAFwt. All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
Receives: Drug: FOLFOX induction regimen; Drug: Bevacizumab; Drug: 5-FU/LV
Cohort 3 (IP)OtherIncludes participants with human epidermal growth factor receptor 2 positive (HER2+). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
Receives: Drug: FOLFOX induction regimen; Drug: Bevacizumab; Drug: 5-FU/LV
Cohort 4 (IP)OtherIncludes participants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut). All participants will receive either eight 2-week cycles of 5-fluorouracil (5-FU)/ leucovorin calcium (LV) and oxaliplatin (FOLFOX) in combination with bevacizumab, or six 2-week cycles of FOLFOX in combination with bevacizumab, followed by two 2-week cycles of 5-FU/LV with bevacizumab.
Receives: Drug: FOLFOX induction regimen; Drug: Bevacizumab; Drug: 5-FU/LV
Cohort 1 (Maintenance Phase[MP]):5-FU/LV,cetuximab,vemurafenibExperimentalParticipants with v-raf murine sarcoma viral oncogene homolog B1 mutation positive (BRAFmut)/human epidermal growth factor receptor 2 negative (HER2-)/microsatellite stable (MSS)/rat sarcoma wild type (RASwt) will receive 1600-2400 milligrams per square meter (mg/m^2) 5-FU via 46-hour intravenous (IV) infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle with 500 mg/m^2 cetuximab via infusion on Day 1 of every 2-week cycle and 960 milligrams (mg) vemurafenib twice daily (BID) by mouth.
Receives: Drug: Cetuximab; Drug: Vemurafenib; Drug: 5-FU/LV
Cohort 1 Control (MP): 5-FU/LV or capecitabin, bevacizumabActive comparatorPer Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Receives: Drug: Fluoropyrimidine (5-FU/LV or capecitabine); Drug: Bevacizumab
Cohort 2 (MP):5-FU/LV or capecitabine,bevacizumab,atezolizumabExperimentalParticipants with BRAFwt will receive fluoropyrimidine (1600-2400 mg/m^2 5-FU via 46-hour IV infusion in combination with 400 mg/m^2 LV via 2-hour infusion on Day 1 of every 2-week cycle or 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break) with 5 milligrams per kilogram (mg/kg) bevacizumab via 15-30 minute IV infusion on Day 1 of every 2-week cycle and 800 mg atezolizumab via 60-minute IV infusion on Day 1 of every 2-week cycle.
Receives: Drug: Fluoropyrimidine (5-FU/LV or capecitabine); Drug: Atezolizumab; Drug: Bevacizumab
Cohort 2 Control (MP): 5-FU/LV or capecitabin, bevacizumabActive comparatorPer Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Receives: Drug: Fluoropyrimidine (5-FU/LV or capecitabine); Drug: Bevacizumab
Cohort 3 (MP): capecitabine,trastuzumab,pertuzumabExperimentalParticipants with human epidermal growth factor receptor 2 positive (HER2+) will receive 1000 mg/m^2 twice-daily capecitabine BID by mouth on Days 1-14 every 2 weeks followed by a 1-week break with trastuzumab by IV infusion on Day 1 of every 3-week treatment cycle at an initial loading dose of 8 mg/kg followed by 6 mg/kg for subsequent doses, and pertuzumab by IV infusion on Day 1 of each 3-week treatment cycle at an initial fixed loading dose of 840 mg followed by 420 mg for subsequent doses.
Receives: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Capecitabine
Cohort 3 Control (MP): 5-FU/LV or capecitabin, bevacizumabActive comparatorPer Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Receives: Drug: Fluoropyrimidine (5-FU/LV or capecitabine); Drug: Bevacizumab
Cohort 4 (MP): Cobimetinib,atezolizumabExperimentalParticipants with HER2-/high microsatellite instability (MSI-H); HER2-/MSS/v-raf murine sarcoma viral oncogene homolog B1 wild type (BRAFwt); HER2-/MSS/BRAFmut/rat sarcoma mutation positive (RASmut) will receive 60 mg cobimetinib orally for 3 weeks followed by a 1-week treatment break and atezolizumab at a fixed dose of 840 mg via 60-minute IV infusion on Day 1 of every 2-week cycle.
Receives: Drug: Atezolizumab; Drug: Cobimetinib
Cohort 4 Control (MP): 5-FU/LV or capecitabin, bevacizumabActive comparatorPer Investigator discretion, participants will receive fluoropyrimidine (5-FU/LV or capecitabine) at a dose and schedule per the Investigator's discretion in accordance with locally approved prescribing information and 5 mg/kg bevacizumab via 1-30 minute IV on Day 1 of every 2-week cycle.
Receives: Drug: Fluoropyrimidine (5-FU/LV or capecitabine); Drug: Bevacizumab
Early Progressing BRAFmut CohortOtherBRAFmut participants experiencing early disease progression during induction treatment will have the option of proceeding immediately to receive second-line treatment with 5-FU/LV, cetuximab and vemurafenib if their primary tumor is MSS, or with a fluoropyrimidine (5-FU/LV or capecitabine), bevacizumab, and atezolizumab if their primary tumor is MSI-H. This cohort will be followed for adverse events during the study, but is not part of the Maintenance Phase study objectives.
Receives: Drug: Cetuximab; Drug: Fluoropyrimidine (5-FU/LV or capecitabine); Drug: Atezolizumab; Drug: Vemurafenib; Drug: Bevacizumab; Drug: 5-FU/LV

What is being measured

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

  1. Progression-Free Survival (PFS)

    PFS is defined as the time from randomization to the first occurrence of disease progression according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.

    Measured: From randomization until disease progression or death from any cause, up to 5 years

Secondary outcomes (7)

  1. Overall Survival (OS)

    OS is defined as the time from randomization into the MTP to time of death from any cause.

    Measured: From randomization until death from any cause, up to 5 years

  2. Percentage of Participants With Adverse Events

    Measured: From baseline until end of study (up to 5 years)

  3. Overall Response

    Calculated as the number of participants with a best overall response of CR or PR according to RECIST 1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR= CR + PR.

    Measured: From randomization until disease progression, up to 5 years

  4. Disease Control Rate (DCR)

    DCR is defined as the percentage of participants with CR, PR, or stable disease (SD) at 16 weeks. Per RECIST v1.1, CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum on study. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions.

    Measured: From randomization until disease progression, up to 5 years

  5. Time to Treatment Response

    Calculated as the time from randomization to the first Occurrence of a documented Objective Response (CR or PR) determined according to RECIST 1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: From randomization until disease progression or death from any cause, up to 5 years

  6. Duration of Response

    Defined as the time from the first assessment of CR or PR until disease progression or death from any cause, whichever occurs first. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: From first objective response until disease progression or death from any cause, up to 5 years

  7. Percentage of Participants With Improvement and/or Stayed the Same on the Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score

    Measured: From baseline until end of study (up to 5 years)

Timeline

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

  1. First posted14 Nov 2014 (estimated)
  2. Study start17 Apr 2015
  3. Primary completion31 May 2019
  4. Study completion24 Mar 2021

Resources

More details

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

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,044 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02291289
Sponsor's protocol ID
MO29112
Other IDs
2014-001017-61, 2014
Acronym
MODUL
Status last verified
Oct 2023
First submitted
11 Nov 2014
Last updated
6 May 2024
Data monitoring committee
Yes

Publications

  • Ducreux M, Tabernero J, Grothey A, Arnold D, O'Dwyer PJ, Gilberg F, Abbas A, Thakur MD, Prizant H, Irahara N, Tahiri A, Schmoll HJ, Van Cutsem E, de Gramont A. Clinical and exploratory biomarker findings from the MODUL trial (Cohorts 1, 3 and 4) of biomarker-driven maintenance therapy for metastatic colorectal cancer. Eur J Cancer. 2023 May;184:137-150. doi: 10.1016/j.ejca.2023.01.023. Epub 2023 Feb 4.

    PubMed 36921494

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cetuximab, FOLFOX induction regimen and Fluoropyrimidine (5-FU/LV or capecitabine) in people with Colorectal Cancer, run by Hoffmann-La Roche at 154 sites in 23 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 8 inclusion and 65 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 6 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 154 sites in Germany, Spain, France, Italy, United Kingdom and 18 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 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?

Progression-Free Survival (PFS) (time frame: From randomization until disease progression or death from any cause, up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02291289, which also lists 1 linked publication.

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 6 May 2024.

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