A Phase 3 interventional study of Erbitux (Cetuximab) and Bevacizumab in Metastatic Colorectal Cancer (mCRC), sponsored by University of Campania Luigi Vanvitelli. Recruiting at 41 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-05.
Sponsored by University of Campania Luigi Vanvitelli · Phase 3, Interventional, and Treatment
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.
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.
6,541 studies on the registry are indexed under Colorectal Neoplasms; 1,667 are open to participants now.
This study's planned enrollment of 480 is above the median of 76 across 4,800 interventional studies indexed under Colorectal Neoplasms.
Browse Colorectal Neoplasms studies →University of Campania Luigi Vanvitelli is the lead sponsor of 174 studies on the registry; 28 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Adequate bone marrow, liver and renal function assessed within 14 days before starting study treatment as defined by the following parameters:
Bone marrow:
Liver function:
Renal function:
If female and of *, 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 unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Erbitux (Cetuximab) · Drug: FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin) · Drug: FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)
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.
Drug: Bevacizumab · Drug: FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin) · Drug: FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)
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
Drug page: Folfox protocol
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.
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.
Time frame: 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.
Overall Survival (OS)
Time from randomization until death due to any cause. Patients alive at last follow-up will be censored at that date.
Time frame: 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.
Time frame: 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.
Time frame: From first treatment administration until 30 days after the last dose.
Started Oct 2025 (actual). Primary completion is estimated for Oct 2030, 60 months after the start.
Of 106 non-industry phase 3 interventional studies under Colorectal Neoplasms, half reached primary completion within 65 months of starting (the median), counting those still running; a quarter within 42 and three quarters within 116. This study's planned 60 months is close to that.
Counting every sponsor, half of 175 studies reached it within 50 months; a quarter within 35 and three quarters within 79.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
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Studies of the drug tested here: Cetuximab
University of Campania Luigi Vanvitelli →