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

ConditionMetastatic Colorectal Cancer (mCRC)
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Campania Luigi Vanvitelli

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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).

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

Treatment groups

480 Participants
are divided into 2 treatment groups
Group A: ARM A Chemo-doublet (FOLFIRI or FOLFOX) + CetuximabExperimental treatment 3 interventions
Group B: ARM B Chemo-doublet (FOLFIRI or FOLFOX) + BevacizumabActive comparator 3 interventions

Trial outcomes

Primary outcomes

1

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.

Secondary outcomes

1

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)
2

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.
3

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.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Campania Luigi Vanvitelli

Lead sponsor

Source ClinicalTrials.gov
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