Metastatic Colorectal Cancer (mCRC)Phase 3CAPRI-3 GOIMNCT07389265
Continuation of Cetuximab Beyond First-Line Progression in Metastatic Colorectal Cancer
A Phase 3 study testing Erbitux (Cetuximab), Bevacizumab and FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin) in people with Metastatic Colorectal Cancer (mCRC), run by University of Campania Luigi Vanvitelli at 41 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer (mCRC)
- What is being tested?
- Erbitux (Cetuximab), Bevacizumab and FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 480 participants
- Where
- 41 sitesin 2 countries
- Study dates
- 1 Oct 2025to Oct 2030
- Phase
- Phase 3
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
- 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).
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- 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:
- 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
- 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.
- A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
- 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 6 months after last dose of study treatment administration, based on the judgment of the Investigator or a designated associate.
- Signed informed consent obtained before screening.
Who cannot join
- 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.
- Pregnancy (exclusion to be ascertained by a beta hCG test).
- Breastfeeding.
- Fertile women (<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.
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- 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).
- 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.
- Participation in a clinical study or experimental drug treatment within 30 days prior to study inclusion or during participation in 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.
- Patients with known dMMR or MSI-H tumors who are eligible for approved immune checkpoint inhibitor therapy will be excluded from the trial, unless ICI therapy is contraindicated or declined by the patient. This ensures alignment with current standard of care.
Trial locations and contacts
41 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
Stefania Napolitano contact
41 sites in 2 countries
Italy30 sites, 30 recruiting
- Not yet recruiting
A.O.U. Ospedali Riuniti
Ancona
Rossana Berardi
- Not yet recruiting
AORN S. Giuseppe Moscati
Avellino
Giuseppe Santabarbara
- Not yet recruiting
Centro di Riferimento Oncologico (C.R.O.) IRCCS
Aviano
Michela Guardascione
- Not yet recruiting
IRCCS Istituto Tumori "Giovanni Paolo II"
Bari
Nicola Silvestris
- Not yet recruiting
Fondazione Poliambulanza Istituto Ospedaliero
Brescia
Michela Libertini
- Not yet recruiting
Ospedale IRCCS 'Saverio de Bellis'
Castellana Grotte
Claudio Lotesoriere
- Not yet recruiting
Nome EnteA.R.N.A.S. Garibaldi - P.O. Garibaldi-Nesima
Catania
Roberto Bordonaro
- Not yet recruiting
Azienda Ospedaliero-Universitaria Renato Dulbecco
Catanzaro
Pierosandro Tagliaferri
- Not yet recruiting
A.O.U. Careggi
Florence
Lorenzo Antonuzzo
- Not yet recruiting
P.O. 'Vito Fazzi'
Lecce
Silvana Leo
- Not yet recruiting
Istituto Romagnolo per lo Studio dei Tumori 'Dino Amadori'
Meldola
Alessandro Passardi
- Not yet recruiting
ASST Grande Ospedale Metropolitano Niguarda
Milan
Andrea Sartore Bianchi
- Not yet recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan
Filippo Pietrantonio
- Not yet recruiting
Istituto Europeo di Oncologia
Milan
Maria Giulia Zampino
- Not yet recruiting
Casa di Cura Villa Maria
Mirabella Eclano
Antonio Febbraro
- Recruiting
A.O.U. dell'Università degli studi della Campania 'Luigi Vanvitelli'
Naples
Fortunato Ciardiello
- Not yet recruiting
A.O.U. Federico II
Naples
Chiara Carlomagno
- Not yet recruiting
IRCCS I.N.T. 'Fondazione G. Pascale'
Naples
Antonio Avallone
- Not yet recruiting
Istituto Oncologico Veneto IRCCS
Padova
Francesca Bergamo
- Not yet recruiting
ARNAS Civico - Di Cristina-Benfratelli - P. O. 'Civico e Benfratelli'
Palermo
Marco Messina
- Not yet recruiting
Casa di cura Macchiarella
Palermo
Alfredo Colombo
- Not yet recruiting
A.O.U. Pisana
Pisa
Chiara Cremolini
- Not yet recruiting
Azienda USL IRCCS di Reggio Emilia
Reggio Emilia
Maria Banzi
- Not yet recruiting
Fondazione Policlinico Universitario 'Agostino Gemelli' IRCCS
Roma
Giampaolo Tortora
- Not yet recruiting
IRCCS Istituto clinico Humanitas
Rozzano
Alberto Puccini
- Not yet recruiting
Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo
Tiziana Pia Latiano
- Not yet recruiting
A.O.U. Sassari
Sassari
Alessio Cogoni
- Not yet recruiting
Ospedale San Giuseppe Moscati
Statte
Salvatore Pisconti
- Not yet recruiting
A.O. 'Pia Fondazione Cardinale G.Panico'
Tricase
Emiliano Tamburini
- Not yet recruiting
IRCCS Ospedale Sacro Cuore Don Calabria
Veneto
Stefania Gori
Spain11 sites, 11 recruiting
- Not yet recruiting
Hospital del Mar
Barcelona
Clara Montagut Viladot
- Not yet recruiting
Hospital Universitari Vall d´Hebron
Barcelona
Francesc Salvà Ballabrera
- Not yet recruiting
Hospital General Universitario Santa Lucía
Cartagena
Paola Pimentel Càceres
- Not yet recruiting
Hospital Universitario Reina Sofía
Córdoba
Maria Jose Ortiz Morales
- Not yet recruiting
Hospital Universitario Virgen de las Nieves
Granada
Encarnaciòn Gonzàles Flores
- Not yet recruiting
Instituto Catalán de Oncología. Hospital Duran i Reynals
L'Hospitalet de Llobregat
Cristina Santos Vivas
- Not yet recruiting
Hospital Universitario 12 de Octubre
Madrid
Cristina Grávalos Castro
- Not yet recruiting
Hospital Universitario Gregorio Marañón
Madrid
Pilar Garcìa Alfonso
- Not yet recruiting
Hospital Universitario Regional de Málaga
Málaga
Julia Alcaide Garcìa
- Not yet recruiting
Hospital Universitario de Navarra
Pamplona
Ruth Vera Garcìa
- Not yet recruiting
Hospital Universitario Marqués de Valdecilla
Santander
Fernando Rivera Herrero
About this study
Official title: 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.
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.
Read the detailed description
Metastatic colorectal cancer (mCRC) is one of the most common and lethal cancers worldwide. Despite progress with chemotherapy and targeted therapies, many patients experience disease progression after first-line treatment. In recent years, drugs targeting the Epidermal Growth Factor Receptor (EGFR), such as cetuximab, have shown significant benefit in patients with RAS and BRAF wild-type tumors. However, it remains unclear whether continuing cetuximab beyond progression, while changing the chemotherapy backbone, can provide additional benefit compared to switching to an alternative targeted treatment.
The CAPRI-3 study is a randomized, multicenter, open-label Phase 3 clinical trial designed to address this question. The study will enroll approximately 360 adult patients with metastatic colorectal cancer in Italy and Spain. All participants must have tumors that are RAS and BRAF wild-type, as well as PIK3CA and EGFR extracellular domain wild-type and HER2 non-amplified, as determined by next-generation sequencing on liquid biopsy at the time of screening. Eligible patients will have previously received a first-line regimen with chemotherapy plus an anti-EGFR antibody (cetuximab or panitumumab) and achieved either a complete or partial response, or prolonged stable disease, before disease progression.
Patients will be randomized in a 1:1 ratio to receive a standard chemotherapy doublet (FOLFOX or FOLFIRI, depending on the regimen used in the first line) combined either with cetuximab (experimental arm) or with bevacizumab (control arm). Treatment will be continued until disease progression, unacceptable toxicity, or withdrawal of consent. Tumor response will be assessed according to RECIST 1.1 criteria by independent central review.
The primary endpoint of the study is objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), and safety profile assessed according to NCI CTCAE version 5.0. Exploratory objectives include biomarker and translational research, involving the collection and analysis of tumor tissue, blood, and stool samples to better understand resistance mechanisms and the role of the gut microbiome in treatment response.
This study builds on promising results from the earlier CAPRI and CAPRI-2 trials, which suggested that continuing cetuximab in second-line therapy may improve patient outcomes. If successful, CAPRI-3 could establish cetuximab continuation beyond first-line progression as a new treatment option for a large proportion of molecularly selected patients with metastatic colorectal cancer.
- Conditions
- Metastatic Colorectal Cancer (mCRC)
- Being tested
- Erbitux (Cetuximab), Bevacizumab, FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin), FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Erbitux (Cetuximab)Drug
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.
BevacizumabDrug
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
FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin)Drug
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.
FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| ARM A Chemo-doublet (FOLFIRI or FOLFOX) + Cetuximab | Experimental | This 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. Receives: Drug: Erbitux (Cetuximab); Drug: FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin); Drug: FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan) |
| ARM B Chemo-doublet (FOLFIRI or FOLFOX) + Bevacizumab | Active comparator | This 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. Receives: Drug: Bevacizumab; Drug: FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin); Drug: FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Time from randomization until death due to any cause. Patients alive at last follow-up will be censored at that date.
Measured: 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)
Time from randomization until the date of first documented disease progression, as assessed by central independent review according to RECIST 1.1 criteria, or death from any cause, whichever occurs first.
Measured: 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)
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.
Measured: From first treatment administration until 30 days after the last dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2026
- Study start1 Oct 2025
- Primary completionOct 2030 (estimated)
- Study completionOct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal Cancer (mCRC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Parallel groups
- Model description
- Patients will be randomized (1:1) into two arms: * Arm A: FOLFOX/FOLFIRI plus cetuximab * Arm B: FOLFOX/FOLFIRI plus bevacizumab
- Masking
- None (open label)
- Enrolment
- 480 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Campania Luigi Vanvitelli
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fortunato Ciardiello, University of Campania Luigi Vanvitelli
- Investigators
- Fortunato Ciardiello, Principal investigator, A.O.U. dell'Università degli studi della Campania "Luigi Vanvitelli"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07389265
- Sponsor's protocol ID
- CAPRI-3- GOIM Study
- Acronym
- CAPRI-3 GOIM
- Status last verified
- May 2025
- First submitted
- 30 Sep 2025
- Last updated
- 5 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No