Clinical trial • Phase III • Oncology

CETUXIMAB for Metastatic colorectal cancer

Phase III trial of CETUXIMAB for Metastatic colorectal cancer.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Metastatic colorectal cancer
Trial Stage
Phase III
Drug Modality
Monoclonal antibody|Small molecule

Key dates

Initial CTIS Submission Date
19-02-2025
First CTIS Authorization Date
12-06-2025

Trial design

Randomised, chemotherapy doublet plus bevacizumab (bevacizumab listed as comparator; bevacizumab route: infusion; dose metadata: maxdailydoseamount 5 mg/kg, doseuomtotal mg/kg). auxiliary chemotherapy agents listed include oxaliplatin, fluorouracil, calcium levofolinate, irinotecan (all infusion routes).-controlled Phase III trial in Spain, Italy.

Randomised
Yes
Comparator
Chemotherapy doublet plus bevacizumab (BEVACIZUMAB listed as comparator; BEVACIZUMAB route: INFUSION; dose metadata: maxDailyDoseAmount 5 mg/kg, doseUomTotal mg/Kg). Auxiliary chemotherapy agents listed include OXALIPLATIN, FLUOROURACIL, CALCIUM LEVOFOLINATE, IRINOTECAN (all infusion routes).
Biomarker Stratified
True, biomarkers: RAS (NRAS and KRAS exon 2,3 and 4), BRAFV600E, PIK3CA, EGFR ECD, HER2 (not amplified); selection: wild-type
Target Sample Size
360
Trial Duration For Participant
1826

Eligibility

Recruits 360 The trial marks vulnerable population selection as true. Exclusion criterion includes: "Absent or restricted legal capacity." Informed consent requirement: "Signed informed consent obtained before screening." Subject information and informed consent forms are provided (documents titled 'Subject information and informed consent form' available in Spanish, Italian and English)..

Pregnancy Exclusion
Pregnancy (exclusion to be ascertained by a beta hCG test).
Vulnerable Population
The trial marks vulnerable population selection as true. Exclusion criterion includes: "Absent or restricted legal capacity." Informed consent requirement: "Signed informed consent obtained before screening." Subject information and informed consent forms are provided (documents titled 'Subject information and informed consent form' available in Spanish, Italian and English).

Inclusion criteria

  • {"criterion_text":"- Histologically proven diagnosis of colorectal adenocarcinoma.\n- Adequate bone marrow, liver and renal function assessed within 14 days before starting study treatment as defined by the following parameters: Bone marrow: • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L • Hemoglobin (Hgb) ≥ 9 g/dL • Platelets ≥ 100 x 109/L Liver function: • Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and ALT (SGPT) ≤ 2.5 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT ≤ 5 x ULN Renal function: • Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min\n- If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment.\n- If female and of childbearing potential, or if male, agreement to use adequate contraception (e.g., abstinence, intrauterine device, oral contraceptive, or double-barrier method), during the study and until at least 3 months after last dose of study treatment administration, based on the judgment of the Investigator or a designated associate.\n- Signed informed consent obtained before screening.\n- Diagnosis of metastatic disease.\n- Efficacy of a first line therapy containing anti-EGFR drug with a major response achieved (i.e. complete or partial response according to RECIST criteria v1.1) or a prolonged (at least 6 months) stable disease.\n- Progression to first line therapy.\n- RAS and BRAF wild-type status of FFPE analysis of primary colorectal cancer and/or related metastasis.\n- RAS (NRAS and KRAS exon 2,3 and 4), BRAFV600E, PIK3CA, EGFR ECD wild-type and HER2 not amplified in liquid biopsy at the time of screening (according to NGS, Foundation/Roche).\n- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST criteria, vers.1.1).\n- Male or female patients ≥ 18 years of age.\n- ECOG Performance Status 0-1."}

Exclusion criteria

  • {"criterion_text":"- Any contraindication to the use of cetuximab, bevacizumab, Irinotecan, 5-FU, oxaliplatin, folic acid.\n- Participation in a clinical study or experimental drug treatment within 30 days prior to study inclusion or during participation in the study.\n- Known or clinically suspected brain metastases\n- History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhea.\n- Severe, non-healing wounds, ulcers or bone fractures\n- Marked proteinuria (nephrotic syndrome).\n- Known DPD deficiency (specific screening not required).\n- Known history of alcohol or drug abuse.\n- A significant concomitant disease which, in the investigating physician's opinion, rules out the patient's participation in the study.\n- Absent or restricted legal capacity.\n- Active uncontrolled infections, active disseminated intravascular coagulation or history of interstitial lung disease.\n- Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix.\n- Pregnancy (exclusion to be ascertained by a beta hCG test).\n- Breastfeeding.\n- Fertile women (<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.\n- Myocardial infarction, unstable angina pectoris, balloon angioplasty (PTCA) with or without stenting within the past 12 months before inclusion in the study, Grade III or IV heart failure (NYHA classification).\n- Cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin.\n- Medical or psychological impairments associated with restricted ability to give consent or not allowing conduct of the study."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The Overall Response Rate (ORR) according to RECIST 1.1 defined as the proportion of patients who have a partial or complete response to therapy. An external radiology department will receive the images of radiological re-evaluations from the participating sites. The imaging will be assessed by a blind operator.","definition_or_measurement_approach":"ORR according to RECIST 1.1 defined as the proportion of patients with partial or complete response; imaging from sites will be sent to an external radiology department and assessed by a blind operator."}

Secondary endpoints

  • {"endpoint_text":"- Progression Free Survival (PFS) according to RECIST 1.1 defined as the time from random assignment in the clinical trial to disease progression or death from any cause.","definition_or_measurement_approach":"PFS per RECIST 1.1 defined as time from random assignment to disease progression or death from any cause."}
  • {"endpoint_text":"- The Overall Survival (OS) defined as the interval from enrollment to death for every cause.","definition_or_measurement_approach":"OS defined as interval from enrollment to death from any cause."}
  • {"endpoint_text":"- The safety profile of the trial drugs as measured by the incidence of AEs, SAEs, clinical laboratory assessments, vital signs, physical examination, ECG parameters, and ECOG PS.","definition_or_measurement_approach":"Safety measured by incidence of adverse events (AEs), serious adverse events (SAEs), clinical labs, vital signs, physical exam, ECG parameters, and ECOG performance status."}

Recruitment

Planned Sample Size
360
Recruitment Window Months
60
Consent Approach
Signed informed consent obtained before screening. Subject information and informed consent forms available (documents titled 'Subject information and informed consent form' present in Spanish, Italian and English). Participants with absent or restricted legal capacity are excluded.

Geography

Total Number Of Sites
38
Total Number Of Participants
360

Spain

Earliest CTIS Part Ii Submission Date
06-05-2025
Latest Decision Or Authorization Date
12-06-2025
Processing Time Days
37
Number Of Sites
11
Number Of Participants
135

Sites

Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncologia Medica
Principal Investigator Name
Cristina Gràvalos Castro
Principal Investigator Email
cgravalos@telefonica.net
Contact Person Name
Cristina Gràvalos Castro
Contact Person Email
cgravalos@telefonica.net
Site Name
Hospital Universitari Vall d’Hebron
Department Name
Oncologia Medica
Principal Investigator Name
Francesc Salvà Bellabrera
Principal Investigator Email
fsalva@vhio.net
Contact Person Name
Francesc Salvà Bellabrera
Contact Person Email
fsalva@vhio.net
Site Name
Hospital General Universitario Santa Lucia
Department Name
Oncologia Medica
Principal Investigator Name
Paola Pimentel Caceres
Principal Investigator Email
paopimentel@yahoo.com
Contact Person Name
Paola Pimentel Caceres
Contact Person Email
paopimentel@yahoo.com
Site Name
Hospital Universitario Virgen De Las Nieves
Department Name
Oncologia Medica
Principal Investigator Name
Encarnacion González Flores
Principal Investigator Email
encarnagonzalezflores@gmail.com
Contact Person Name
Encarnacion González Flores
Site Name
Hospital Universitario Marqués de Valdecilla
Department Name
Oncologia Medica
Principal Investigator Name
Fernando Rivera Herrero
Principal Investigator Email
fernando.rivera@scsalud.es
Contact Person Name
Fernando Rivera Herrero
Contact Person Email
fernando.rivera@scsalud.es
Site Name
Hospìtal General Universitario Gregorio Marañón
Department Name
Oncologia Medica
Principal Investigator Name
Pilar Garcia Alfonso
Principal Investigator Email
pgarcaalfonso@gmail.com
Contact Person Name
Pilar Garcia Alfonso
Contact Person Email
pgarcaalfonso@gmail.com
Site Name
Hospital Regional Universitario de Málaga
Department Name
Oncologia Medica
Principal Investigator Name
Julia Alcaide Garcìa
Principal Investigator Email
drayulia@hotmail.com
Contact Person Name
Julia Alcaide Garcìa
Contact Person Email
drayulia@hotmail.com
Site Name
Hospital Universitario De Navarra
Department Name
Oncologia Medica
Principal Investigator Name
Ruth Vera Garcìa
Principal Investigator Email
ruth.vera.garcia@navarra.es
Contact Person Name
Ruth Vera Garcìa
Contact Person Email
ruth.vera.garcia@navarra.es
Site Name
Hospital Universitario Reina Sofia
Department Name
Oncologia Medica
Principal Investigator Name
Jose Ortiz Morales
Principal Investigator Email
emejota11@hotmail.com
Contact Person Name
Jose Ortiz Morales
Contact Person Email
emejota11@hotmail.com
Site Name
Hospital Del Mar
Department Name
Oncologia Medica
Principal Investigator Name
Clara Montagut Viladot
Principal Investigator Email
cmontagut@psmar.cat
Contact Person Name
Clara Montagut Viladot
Contact Person Email
cmontagut@psmar.cat
Site Name
ICO L'HOSPITALET HOSPITAL DURAN I REYNALS
Department Name
Oncologia Medica
Principal Investigator Name
Cristina Santos Vivas,
Principal Investigator Email
csantos@iconcologia.net
Contact Person Name
Cristina Santos Vivas,
Contact Person Email
csantos@iconcologia.net

Italy

Earliest CTIS Part Ii Submission Date
09-05-2025
Latest Decision Or Authorization Date
19-01-2026
Processing Time Days
255
Number Of Sites
27
Number Of Participants
225

Sites

Site Name
Ospedale Vito Fazzi Lecce
Department Name
U.O. Oncologia Medica
Principal Investigator Name
Silvana Leo
Principal Investigator Email
silvileo59@gmail.com
Contact Person Name
Silvana Leo
Contact Person Email
silvileo59@gmail.com
Site Name
Istituto Tumori Bari Giovanni Paolo II
Department Name
SC Oncologia Medica
Principal Investigator Name
Nicola Silvestris
Principal Investigator Email
nicola.silvestris@unime.it
Contact Person Name
Nicola Silvestris
Contact Person Email
nicola.silvestris@unime.it
Site Name
Casa Di Cura Macchiarella S.p.A.
Department Name
Oncologia Medica
Principal Investigator Name
Alfredo Colombo
Principal Investigator Email
alfredo.colombo@tin.it
Contact Person Name
Alfredo Colombo
Contact Person Email
alfredo.colombo@tin.it
Site Name
ASST Grande Ospedale Metropolitano Niguarda
Department Name
Oncologia Medica Falck
Principal Investigator Name
Andrea Sartore Bianchi
Principal Investigator Email
andrea.sartorebianchi@unimi.it
Contact Person Name
Andrea Sartore Bianchi
Contact Person Email
andrea.sartorebianchi@unimi.it
Site Name
Azienda Ospedaliera Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
U.O.C. Oncoematologia
Principal Investigator Name
Fortunato Ciardiello
Principal Investigator Email
fortunato.ciardiello@unicampania.it
Contact Person Name
Fortunato Ciardiello
Site Name
Casa Sollievo Della Sofferenza
Department Name
U.O.C. Oncoogia
Principal Investigator Name
Tiziana Pia Latiano
Principal Investigator Email
latiano.tiziana@gmail.com
Contact Person Name
Tiziana Pia Latiano
Contact Person Email
latiano.tiziana@gmail.com
Site Name
Istituto Europeo Di Oncologia S.r.l.
Department Name
Divisione di Oncologia Medica Gastrointestinale e Tumori
Principal Investigator Name
Maria Zampino
Principal Investigator Email
maria.zampino@ieo.it
Contact Person Name
Maria Zampino
Contact Person Email
maria.zampino@ieo.it
Site Name
Ospedale S G Moscati
Department Name
Oncologia Medica
Principal Investigator Name
Salvatore Pisconti
Principal Investigator Email
salvatore.pisconti@asl.taranto.it
Contact Person Name
Salvatore Pisconti
Site Name
Azienda Ospedaliero Universitaria Careggi
Department Name
Oncologia Medica
Principal Investigator Name
Lorenzo Antonuzzo
Principal Investigator Email
lorenzo.antonuzzo@unifi.it
Contact Person Name
Lorenzo Antonuzzo
Contact Person Email
lorenzo.antonuzzo@unifi.it
Site Name
Azienda USL IRCCS Di Reggio Emilia
Department Name
S.C. Oncologia Provinciale
Principal Investigator Name
Maria Banzi
Principal Investigator Email
maria.banzi@ausl.re.it
Contact Person Name
Maria Banzi
Contact Person Email
maria.banzi@ausl.re.it
Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
S.C. Oncologia Clinica Sperimentale Addome
Principal Investigator Name
Antonio Avallone
Principal Investigator Email
a.avallone@istitutotumori.na.it
Contact Person Name
Antonio Avallone
Site Name
Centro Di Riferimento Oncologico Di Aviano
Department Name
S.O.C. Oncologia Medica e Prevenzione Oncologica
Principal Investigator Name
Michela Guardascione
Principal Investigator Email
michela.guardascione@cro.it
Contact Person Name
Michela Guardascione
Contact Person Email
michela.guardascione@cro.it
Site Name
IRCCS Ospedale Sacro Cuore Don Calabria
Department Name
Oncologia medica
Principal Investigator Name
Stefania Gori
Principal Investigator Email
stefania.gori@sacrocuore.it
Contact Person Name
Stefania Gori
Contact Person Email
stefania.gori@sacrocuore.it
Site Name
ARNAS Garibaldi Di Catania
Department Name
U.O.C. Oncologia Medica
Principal Investigator Name
Roberto Bordonaro
Principal Investigator Email
sconcologiamedicagaribaldi@outlook.it
Contact Person Name
Roberto Bordonaro
Site Name
Fondazione Poliambulanza
Department Name
Fondazione Poliambulanza Istituto Ospedaliero
Principal Investigator Name
Michela Libertini
Principal Investigator Email
michela.libertini@poliambulanza.it
Contact Person Name
Michela Libertini
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
U.O.C. Oncoogia Medica
Principal Investigator Name
Giampaolo Tortora
Principal Investigator Email
giampaolo.tortora@policlinicogemelli.it
Contact Person Name
Giampaolo Tortora
Site Name
Pia Fondazione Di Culto E Religione Card G Panico
Department Name
U.O. Oncologia
Principal Investigator Name
Emiliano Tamburini
Principal Investigator Email
emilianotamburini@icloud.com
Contact Person Name
Emiliano Tamburini
Contact Person Email
emilianotamburini@icloud.com
Site Name
Azienda Ospedaliero Universitaria Di Sassari
Department Name
U.O. Oncologia
Principal Investigator Name
Alessio Cogoni
Principal Investigator Email
alessio.cogoni@aouss.it
Contact Person Name
Alessio Cogoni
Contact Person Email
alessio.cogoni@aouss.it
Site Name
Azienda Ospedaliero Universitaria Renato Dulbecco
Department Name
U.O.C. Oncologia Medica
Principal Investigator Name
Pierosandro Tagliaferri
Principal Investigator Email
tagliaferri@unicz.it
Contact Person Name
Pierosandro Tagliaferri
Contact Person Email
tagliaferri@unicz.it
Site Name
Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I G M Lancisi G Salesi
Department Name
S.O.D. Clinica Oncologica
Principal Investigator Name
Rossana Berardi
Principal Investigator Email
rossana.berardi@ospedaliriuniti.marche.it
Contact Person Name
Rossana Berardi
Site Name
ARNAS Civico Di Cristina Benfratelli
Department Name
U.O. Oncologia Medica
Principal Investigator Name
Marco Messina
Principal Investigator Email
marco.messina@arnascivico.it
Contact Person Name
Marco Messina
Contact Person Email
marco.messina@arnascivico.it
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
S.C. Oncologia Medica
Principal Investigator Name
Alessandro Passardi
Principal Investigator Email
alessandro.passardi@irst.emr.it
Contact Person Name
Alessandro Passardi
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
OM1 - Oncologia Medica 1
Principal Investigator Name
Filippo Pietrantonio
Principal Investigator Email
filippo.pietrantonio@istitutotumori.mi.it
Contact Person Name
Filippo Pietrantonio
Site Name
National Institute Of Gastroenterology Saverio De Bellis Research Hospital
Department Name
U.O. Oncologia Medica
Principal Investigator Name
Claudio Lotesoriere
Principal Investigator Email
claudio.lotesoriere@irccsdebellis.it
Contact Person Name
Claudio Lotesoriere
Site Name
Humanitas Mirasole S.p.A.
Department Name
U.O. Oncologia medica ed ematologia
Principal Investigator Name
Alberto Puccini
Principal Investigator Email
alberto.puccini@cancercenter.humanitas.it
Contact Person Name
Alberto Puccini
Site Name
AORN San Giuseppe Moscati Avellino
Department Name
U.O.C. Oncologia Medica
Principal Investigator Name
Giuseppe Santabarbara
Principal Investigator Email
giuseppe.santabarbara@aornmoscati.it
Contact Person Name
Giuseppe Santabarbara
Site Name
Casa di Cura Villa Maria
Department Name
Oncologia
Principal Investigator Name
Antonio Febbraro
Principal Investigator Email
antoniofebbraro@virgilio.it
Contact Person Name
Antonio Febbraro
Contact Person Email
antoniofebbraro@virgilio.it

Sponsor

Primary sponsor

Full Name
Gruppo Oncologico Dell'Italia Meridionale
Organisation Type
Patient organisation/association
Country Of Registered Address
Italy

Investigational products

Investigational Product Name
CETUXIMAB
Active Substance
CETUXIMAB
Modality
Monoclonal antibody
Routes Of Administration
INFUSION
Route
INFUSION
Maximum Dose
maxDailyDoseAmount: 500 mg/m2; maxTotalDoseAmount: 12000 mg/m2
Investigational Product Name
BEVACIZUMAB
Active Substance
BEVACIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
INFUSION
Route
INFUSION
Maximum Dose
maxDailyDoseAmount: 5 mg/kg; maxTotalDoseAmount: 130 mg/Kg
Investigational Product Name
OXALIPLATIN
Active Substance
OXALIPLATIN
Modality
Small molecule
Routes Of Administration
INFUSION
Route
INFUSION
Maximum Dose
maxDailyDoseAmount: 85 mg/m2; maxTotalDoseAmount: 2125 mg/m2
Investigational Product Name
FLUOROURACIL
Active Substance
FLUOROURACIL
Modality
Small molecule
Routes Of Administration
INFUSION
Route
INFUSION
Maximum Dose
maxDailyDoseAmount: 2400 mg/m2; maxTotalDoseAmount: 60000 mg/m2
Investigational Product Name
CALCIUM LEVOFOLINATE
Active Substance
CALCIUM LEVOFOLINATE
Modality
Small molecule
Routes Of Administration
INFUSION/INJECTION
Route
SOLUTION FOR INJECTION/INFUSION
Maximum Dose
maxDailyDoseAmount: 200 mg/m2; maxTotalDoseAmount: 5000 mg/m2
Investigational Product Name
IRINOTECAN
Active Substance
IRINOTECAN
Modality
Small molecule
Routes Of Administration
INFUSION
Route
INFUSION
Maximum Dose
maxDailyDoseAmount: 180 mg/m2; maxTotalDoseAmount: 4500 mg/m2
Combination Treatment
Yes

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