NCT07389265

Continuation of Cetuximab Beyond First-Line Progression in 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.

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 480 (estimated)
• Sponsor: University of Campania Luigi Vanvitelli · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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)

Interventions

Type	Name	Description
DRUG	Erbitux (Cetuximab)	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.
DRUG	Bevacizumab	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	FOLFOX (Folinic acid + Fluorouracil + Oxaliplatin)	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.
DRUG	FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan)	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.

Timeline

• Start date: 2025-10-01
• Primary completion: 2030-10-01
• Completion: 2030-10-01
• First posted: 2026-02-05
• Last updated: 2026-02-05

Locations

41 sites across 2 countries: Italy, Spain