Anti-EGFR Agents in Patients With Right-sided Advanced Colorectal Cancer With Wild-type RAS and AREG/EREG High Status

NCT07094893 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: ARIEL-ENGIC
• Study Type: interventional
• Target: 280
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of this trial is to assess the feasibility of EREG/AREG assessment as a clinical diagnostic standard, used to guide clinical decision making in right-PTL, RAS-wt aCRC. Further to this, the aim is to determine whether EREG/AREG status identifies right-PTL participants who will benefit from the addition of anti-EGFR therapy to first-line chemotherapy.

Conditions

Colorectal Cancer

Keywords

metastatic colorectal cancer; first-line; right primary tumour location; AREG; EREG; RAS wild-type; anti-EGFR

Outcome Measures

Primary Outcomes (2)

• Early tumour shrinkage (ETS)

  To determine whether first-line chemotherapy (doublet) with cetuximab is more effective than chemotherapy (doublet or triplet) with or without bevacizumab in achieving early tumour shrinkage (ETS) after 8 weeks of treatment in randomised patients.

  8 weeks after treatment start

• Overall survival (OS)

  To assess whether the effectiveness of first-line chemotherapy (doublet) with cetuximab is more effective than chemotherapy (doublet or triplet) with or without bevacizumab in terms of overall survival (OS).

  50 months

Secondary Outcomes (9)

• Depth of response (DpR)

  24 months

• Objective Response Rate (ORR)

  24 months

• Progression-free survival (PFS)

  24 months

• Overall Toxicity Rate

  24 months

• Toxicity Rate

  24 months

Study Arms (2)

Doublet or Triplet +/- Bevacizumab

ACTIVE COMPARATOR

FOLFOX or CAPOX or FOLFIRI or FOLFOXIRI +/- bevacizumab. Treatment regimen and the dosage of each product in both arms will be at Investigators' discretion and in accordance with European guidelines (ESMO). Chemotherapy backbone is at investigators' choice as per clinical practice and guidelines according to the labels of each IMP. Choice of regimen will depend upon individual patient characteristics and choices, as judged by their oncologist. The choice of adding or not bevacizumab will be at investigators' evaluation according to its label and after evaluating any contraindication to its administration. The study treatment consists of the first 16 weeks of 1st line induction chemotherapy, followed by continuation of chemotherapy +/- bevacizumab, maintenance treatment or treatment break as per investigator and patient preference.

Drug: Bevacizumab; Drug: Irinotecan (CPT-11); Drug: Oxaliplatin; Drug: Leucovorin and 5-FU; Drug: Capecitabine

Doublet + Cetuximab

EXPERIMENTAL

FOLFOX or FOLFIRI + Cetuximab. Treatment regimen and the dosage of each product in both arms will be at Investigators' discretion and in accordance with European guidelines (ESMO). Chemotherapy backbone is at investigators' choice as per clinical practice and guidelines according to the labels of each IMP. The study treatment consists of the first 16 weeks of 1st line induction chemotherapy, followed by continuation of chemotherapy + cetuximab, maintenance treatment or treatment break as per investigator and patient preference.

Drug: Cetuximab (EGFR inhibitor); Drug: Irinotecan (CPT-11); Drug: Oxaliplatin; Drug: Leucovorin and 5-FU

Interventions

Cetuximab (EGFR inhibitor) DRUG

Administration according to the labels of each IMP.

Doublet + Cetuximab

Bevacizumab DRUG

Administration according to the labels of each IMP.

Doublet or Triplet +/- Bevacizumab

Irinotecan (CPT-11) DRUG

Administration according to the labels of each IMP.

Doublet + Cetuximab; Doublet or Triplet +/- Bevacizumab

Oxaliplatin DRUG

Administration according to the labels of each IMP.

Doublet + Cetuximab; Doublet or Triplet +/- Bevacizumab

Leucovorin and 5-FU DRUG

Administration according to the labels of each IMP.

Doublet + Cetuximab; Doublet or Triplet +/- Bevacizumab

Capecitabine DRUG

Administration according to the labels of each IMP.

Doublet or Triplet +/- Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Biopsy-confirmed adenocarcinoma of the colon with a right primary tumour location
• aCRC defined as either M1 or locally inoperable disease
• Tumour RAS status either wild-type (by local testing) or unknown
• Fit for combination chemotherapy plus anti-EGFR agent
• Sufficient tumour material for EREG/AREG analysis
• Written informed consent for registration

You may not qualify if:

• Tumour RAS-mutation present
• Prior chemotherapy for aCRC
• Prior anti-EGFR agent therapy
• Registered in ARIEL-ENGIC
• Local testing confirms tumour RAS-wt status
• ARIEL-ENGIC central testing confirms tumour EREG/AREG high
• Tumour measurable by RECIST v1.1 criteria on CT scan
• Participants have had CT scan within the timeframes stipulated (If there is a contrast reaction, then non-contrast CT with MRI is acceptable, assuming at least one of these modalities shows measurable disease at baseline for ETS evaluation and both modalities are repeated at the trial timepoints at week 8 and 16 and every 8 weeks until disease progression.)
• Pre-randomisation laboratory tests :
• Neutrophils ≥1.5 x109/l and platelet count ≥100 x109/l
• Serum bilirubin ≤ 1.25 x upper limit of normal (ULN), alkaline phosphatase
• x ULN, and serum transaminase (either AST or ALT) ≤ 2.5 x ULN
• Estimated creatinine clearance ≥50ml/min (creatinine clearance estimated as per local practice)
• WHO performance status (PS) 0, 1 or 2
• Fit for combination chemotherapy plus anti-EGFR agent

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead
• Merck Serono International SA: collaborator

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Bevacizumab; Irinotecan; Oxaliplatin; Leucovorin; Fluorouracil; Capecitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Chiara Cremolini, MD, PhD

  Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa

  STUDY CHAIR

Central Study Contacts

Laura Delliponti

CONTACT

+39050992192; laura.delliponti@gmail.com

Ariel Engic

CONTACT

+39050992192; ariel.engic.eu@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2025
• First Posted: July 31, 2025
• Study Start: April 15, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2030
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share