Continuation of Cetuximab Beyond First-Line Progression in Metastatic Colorectal Cancer

Sponsor
University of Campania Luigi Vanvitelli
Study ID
NCT07389265
Phase
PHASE3
Status
Recruiting
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Conditions

  • Metastatic Colorectal Cancer (mCRC)

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • 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.
  • Bevacizumab — DRUG
    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 Details

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.

Key Dates

Start date
Oct 1, 2025
Status verified
May 2025
Primary completion
Oct 31, 2030
Completion
Oct 31, 2030

Study Design

Enrollment
480 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: ARM A Chemo-doublet (FOLFIRI or FOLFOX) + Cetuximab
    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.
  • Active Comparator: ARM B Chemo-doublet (FOLFIRI or FOLFOX) + Bevacizumab
    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.

Primary Outcome Measure

Overall Response Rate (ORR) [ 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. ]

Central Contacts

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