Continuation of Cetuximab Beyond First-Line Progression in Metastatic Colorectal Cancer
CAPRI-3 GOIM
CAPRI-3 GOIM Study: Phase 3 Clinical Study to Evaluate the Use of Continuing Cetuximab Treatment Beyond First Line Progression in Molecular Selected Metastatic Colorectal Cancer Patients.
1 other identifier
interventional
480
2 countries
41
Brief Summary
The goal of this Phase 3 clinical trial is to evaluate whether continuing cetuximab treatment beyond first-line progression can improve outcomes in patients with metastatic colorectal cancer whose tumors are RAS and BRAF wild-type. The study will compare the effectiveness of chemotherapy given together with cetuximab versus chemotherapy given together with bevacizumab. Researchers aim to determine whether cetuximab continuation improves tumor response, progression-free survival, overall survival, and safety in this patient population. Eligible participants are adults with metastatic colorectal cancer who have previously responded to first-line treatment with chemotherapy combined with an anti-EGFR antibody. Before starting therapy, patients will undergo molecular testing using liquid biopsy to confirm tumor characteristics. They will then receive chemotherapy with either cetuximab or bevacizumab every two weeks, and their disease will be monitored regularly with CT or MRI scans, laboratory tests, and clinical evaluations. During the study, patients will also provide biological samples for translational research. This trial will enroll about 360 patients across sites in Italy and Spain and is designed to provide new evidence on whether cetuximab continuation beyond first-line treatment can offer a meaningful clinical benefit compared with standard therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Oct 2025
Longer than P75 for phase_3
41 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 30, 2025
CompletedStudy Start
First participant enrolled
October 1, 2025
CompletedFirst Posted
Study publicly available on registry
February 5, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2030
February 5, 2026
May 1, 2025
5 years
September 30, 2025
February 4, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Response Rate (ORR)
The primary outcome is the Objective Response Rate, which will be evaluated according to the RECIST criteria 1.1. The study aims to determine if the continuous use of cetuximab in the experimental arm results in a superior Response Rate compared to the control arm with bevacizumab.
From date of randomization until the date of first documented progression or date of death from any cause, or study completion whichever came first, assessed until 48 months.
Secondary Outcomes (3)
Overall Survival (OS)
From randomization (Day 0) until death from any cause, assessed through study completion (up to 36 months of survival follow-up)
Progression-Free Survival (PFS)
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months from last patient randomized.
Safety Profile: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
From first treatment administration until 30 days after the last dose.
Study Arms (2)
ARM A Chemo-doublet (FOLFIRI or FOLFOX) + Cetuximab
EXPERIMENTALThis arm is for participants with RAS/BRAF wild-type metastatic colorectal cancer who have progressed after first-line anti-EGFR therapy. They will receive a second-line chemotherapy regimen (either FOLFIRI or FOLFOX) in combination with cetuximab. The objective is to evaluate the efficacy of continuing cetuximab beyond progression.
ARM B Chemo-doublet (FOLFIRI or FOLFOX) + Bevacizumab
ACTIVE COMPARATORThis arm is for participants with RAS/BRAF wild-type metastatic colorectal cancer who have progressed after first-line anti-EGFR therapy. They will receive a second-line chemotherapy regimen (either FOLFIRI or FOLFOX) in combination with bevacizumab. This arm serves as the control group to compare the outcomes with the experimental arm.
Interventions
This is an anti-EGFR monoclonal antibody administered in combination with chemotherapy. The dose is 500 mg/m² administered every 14 days as a 120-minute intravenous infusion on cycle 1 day 1, infusion rate not faster than 5mg/min.
This is an anti-VEGF monoclonal antibody used as an active comparator in the control arm of the study. The dose is 5 mg/kg of body weight, administered every 14 days
This is a standard chemotherapy regimen containing irinotecan, fluorouracil, and folinic acid. It is used as the backbone chemotherapy in both study arms. The dose includes 200 mg/m2 L-folinic acid given concurrently with 85 mg/ m² oxaliplatin over 2 h IV, followed by a 400 mg/ m² IV bolus of fluorouracil followed by 2400 mg/ m² fluorouracil IV infusion every 14 days.
This is a standard chemotherapy regimen containing folinic acid, oxaliplatin, and fluorouracil. It is used as the backbone chemotherapy in both study arms. The dose includes 200 mg/m2 L-folinic acid given concurrently with 180 mg/ m² irinotecan over 1.30 h IV infusion, followed by a 400 mg/ m² IV bolus of fluorouracil followed by 2400 mg/ m² fluorouracil IV infusion over 46 h every 14 days.
Eligibility Criteria
You may qualify if:
- Histologically proven diagnosis of colorectal adenocarcinoma.
- Diagnosis of metastatic disease.
- 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.
- Progression to first line therapy.
- RAS and BRAF wild-type status of FFPE analysis of primary colorectal cancer and/or related metastasis.
- 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).
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST criteria, vers.1.1).
- Male or female patients ≥ 18 years of age.
- ECOG Performance Status 0-1.
- 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:
- +7 more criteria
You may not qualify if:
- Any contraindication to the use of cetuximab, bevacizumab, Irinotecan, 5-FU, oxaliplatin, folic acid.
- Active uncontrolled infections, active disseminated intravascular coagulation or history of interstitial lung disease.
- 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.
- Breastfeeding.
- Fertile women (\<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.
- Cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin.
- Medical or psychological impairments associated with restricted ability to give consent or not allowing conduct of the study.
- Known or clinically suspected brain metastases.
- History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhea.
- Severe, non-healing wounds, ulcers or bone fractures.
- Marked proteinuria (nephrotic syndrome).
- Known DPD deficiency (specific screening not required).
- Known history of alcohol or drug abuse.
- A significant concomitant disease which, in the investigating physician's opinion, rules out the patient's participation in the study.
- Absent or restricted legal capacity.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (41)
A.O.U. Ospedali Riuniti
Ancona, Italy
AORN S. Giuseppe Moscati
Avellino, Italy
Centro di Riferimento Oncologico (C.R.O.) IRCCS
Aviano, Italy
IRCCS Istituto Tumori "Giovanni Paolo II"
Bari, Italy
Fondazione Poliambulanza Istituto Ospedaliero
Brescia, Italy
Ospedale IRCCS 'Saverio de Bellis'
Castellana Grotte, Italy
Nome EnteA.R.N.A.S. Garibaldi - P.O. Garibaldi-Nesima
Catania, Italy
Azienda Ospedaliero-Universitaria Renato Dulbecco
Catanzaro, Italy
A.O.U. Careggi
Florence, Italy
P.O. 'Vito Fazzi'
Lecce, Italy
Istituto Romagnolo per lo Studio dei Tumori 'Dino Amadori'
Meldola, Italy
ASST Grande Ospedale Metropolitano Niguarda
Milan, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy
Istituto Europeo di Oncologia
Milan, Italy
Casa di Cura Villa Maria
Mirabella Eclano, Italy
A.O.U. dell'Università degli studi della Campania 'Luigi Vanvitelli'
Naples, Italy
A.O.U. Federico II
Naples, Italy
IRCCS I.N.T. 'Fondazione G. Pascale'
Naples, Italy
Istituto Oncologico Veneto IRCCS
Padua, Italy
ARNAS Civico - Di Cristina-Benfratelli - P. O. 'Civico e Benfratelli'
Palermo, Italy
Casa di cura Macchiarella
Palermo, Italy
A.O.U. Pisana
Pisa, Italy
Azienda USL IRCCS di Reggio Emilia
Reggio Emilia, Italy
Fondazione Policlinico Universitario 'Agostino Gemelli' IRCCS
Roma, Italy
IRCCS Istituto clinico Humanitas
Rozzano, Italy
Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo, Italy
A.O.U. Sassari
Sassari, Italy
Ospedale San Giuseppe Moscati
Statte, Italy
A.O. 'Pia Fondazione Cardinale G.Panico'
Tricase, Italy
IRCCS Ospedale Sacro Cuore Don Calabria
Veneto, Italy
Hospital del Mar
Barcelona, Spain
Hospital Universitari Vall d´Hebron
Barcelona, Spain
Hospital General Universitario Santa Lucía
Cartagena, Spain
Hospital Universitario Reina Sofía
Córdoba, Spain
Hospital Universitario Virgen de las Nieves
Granada, Spain
Instituto Catalán de Oncología. Hospital Duran i Reynals
L'Hospitalet de Llobregat, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital Universitario Gregorio Marañón
Madrid, Spain
Hospital Universitario Regional de Málaga
Málaga, Spain
Hospital Universitario de Navarra
Pamplona, Spain
Hospital Universitario Marqués de Valdecilla
Santander, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Fortunato Ciardiello
A.O.U. dell'Università degli studi della Campania "Luigi Vanvitelli"
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
September 30, 2025
First Posted
February 5, 2026
Study Start
October 1, 2025
Primary Completion (Estimated)
October 1, 2030
Study Completion (Estimated)
October 1, 2030
Last Updated
February 5, 2026
Record last verified: 2025-05