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Continuing cetuximab after first progression for metastatic colorectal cancer

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.

Phase 3 Interventional University of Campania Luigi Vanvitelli · NCT07389265

This study will test whether keeping cetuximab while switching the chemotherapy backbone helps adults with RAS/BRAF wild‑type metastatic colorectal cancer whose disease progressed after first‑line anti‑EGFR therapy.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment480 (estimated)
Ages18 Years and up
SexAll
SponsorUniversity of Campania Luigi Vanvitelli Academic / other
Drugs / interventionscetuximab, bevacizumab, chemotherapy, panitumumab
Locations41 sites (Ancona and 40 other locations)
Trial IDNCT07389265 on ClinicalTrials.gov

What this trial studies

This is a randomized, open‑label Phase 3 trial enrolling about 360 adults in Italy and Spain who previously responded to first‑line chemotherapy plus an anti‑EGFR antibody. All participants must have RAS and BRAF wild‑type tumors and additional molecular criteria confirmed by liquid‑biopsy NGS before randomization. Patients are assigned 1:1 to receive a standard chemotherapy doublet (FOLFOX or FOLFIRI) combined either with cetuximab or with bevacizumab and will undergo regular CT or MRI scans to monitor disease. Primary outcomes include tumor response, progression‑free survival, overall survival, and safety across the two arms.

Who should consider this trial

Good fit: Adults (≥18) with metastatic colorectal adenocarcinoma who had a major response or at least six months of stable disease on first‑line chemotherapy plus an anti‑EGFR antibody and whose tumors are RAS, BRAFV600E, PIK3CA, and EGFR ECD wild‑type with no HER2 amplification on liquid biopsy are ideal candidates.

Not a fit: Patients with RAS or BRAF mutations, HER2 amplification, poor performance status (ECOG ≥2), or those who did not derive prior benefit from anti‑EGFR first‑line therapy are unlikely to benefit from cetuximab continuation.

Why it matters

Potential benefit: If successful, continuing cetuximab beyond first progression could prolong tumor control and survival by maintaining EGFR blockade while changing the chemotherapy backbone.

How similar studies have performed: EGFR antibodies have proven benefit in RAS/BRAF wild‑type mCRC, but prior data on continuing EGFR blockade beyond progression are limited and have shown mixed results, so this approach remains unproven.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Histologically proven diagnosis of colorectal adenocarcinoma.
2. Diagnosis of metastatic disease.
3. 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.
4. Progression to first line therapy.
5. RAS and BRAF wild-type status of FFPE analysis of primary colorectal cancer and/or related metastasis.
6. 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).
7. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST criteria, vers.1.1).
8. Male or female patients ≥ 18 years of age.
9. ECOG Performance Status 0-1.
10. 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
11. 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.
12. 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.
13. Signed informed consent obtained before screening.

Exclusion Criteria:

1. Any contraindication to the use of cetuximab, bevacizumab, Irinotecan, 5-FU, oxaliplatin, folic acid.
2. Active uncontrolled infections, active disseminated intravascular coagulation or history of interstitial lung disease.
3. 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.
4. Pregnancy (exclusion to be ascertained by a beta hCG test).
5. Breastfeeding.
6. Fertile women (\<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.
7. 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).
8. Cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin.
9. Medical or psychological impairments associated with restricted ability to give consent or not allowing conduct of the study.
10. Participation in a clinical study or experimental drug treatment within 30 days prior to study inclusion or during participation in the study.
11. Known or clinically suspected brain metastases.
12. History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhea.
13. Severe, non-healing wounds, ulcers or bone fractures.
14. Marked proteinuria (nephrotic syndrome).
15. Known DPD deficiency (specific screening not required).
16. Known history of alcohol or drug abuse.
17. A significant concomitant disease which, in the investigating physician's opinion, rules out the patient's participation in the study.
18. Absent or restricted legal capacity.
19. 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.

Where this trial is running

Ancona and 40 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Colorectal Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.