A Phase 4 interventional study of Cetuximab (EGFR inhibitor) and Bevacizumab in Colorectal Cancer, sponsored by Gruppo Oncologico del Nord-Ovest. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-24.
Sponsored by Gruppo Oncologico del Nord-Ovest · Phase 4, Interventional, and Treatment
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.
ARIEL-ENGIC is a multi-centre, phase IV, open label, randomised controlled biomarker enrichment trial with an internal pilot phase in which participants with wild-type RAS, right-PTL and EREG/AREG high aCRC will be randomized in a 1:1 ratio to receive chemotherapy (doublet) plus cetuximab versus chemotherapy (doublet or triplet) alone or with bevacizumab.
ARIEL-ENGIC is an international trial in which the UK (recruitment ongoing) and EU (Italy, Germany and Spain) are participating. ARIEL-ENGIC aims to randomize 280 participants at a global level. In Europe 60 centers will be involved and 120 participants (40 pts per Member State involved) will be randomized.
Given the biomarker prevalence, 660 participants will be registered to identify sufficient RAS-wt participants with high tumour EREG/AREG expression.
The ARIEL-ENGIC study has 2 phases, registration and randomization (the main trial). Participants meeting all of the inclusion criteria and none of the exclusion criteria for registration will be considered for trial eligibility and biomarker analysis. Tumour samples will be sent for centralized biomarker (EREG/AREG) assessment. Participants with high tumour EREG/AREG will be eligible for randomisation. Participants eligible for the randomisation phase will be allocated 1:1 to chemotherapy alone or with bevacizumab or chemotherapy plus anti-EGFR agent.
Stratification factors will be:
5,599 studies on the registry are indexed under Colorectal Neoplasms; 1,459 are open to participants now.
This study's planned enrollment of 280 is above the median of 77 across 4,123 interventional studies indexed under Colorectal Neoplasms.
Browse Colorectal Neoplasms studies →Gruppo Oncologico del Nord-Ovest is the lead sponsor of 38 studies on the registry; 11 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria for Registration:
Exclusion Criteria for Registration
Inclusion Criteria for Randomisation:
Serum bilirubin ≤ 1.25 x upper limit of normal (ULN), alkaline phosphatase
Exclusion Criteria for Randomisation:
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
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
Administration according to the labels of each IMP.
Administration according to the labels of each IMP.
Administration according to the labels of each IMP.
Administration according to the labels of each IMP.
Administration according to the labels of each IMP.
Administration according to the labels of each IMP.
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.
Time frame: 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).
Time frame: 50 months
Depth of response (DpR)
Depth of response (DpR) is defined as the maximum tumour shrinkage of RECIST target lesions at the nadir, in the absence of new lesions or progression of non-target lesions, when compared with baseline, assessed at 16 weeks from start of treatment.
Time frame: 24 months
Objective Response Rate (ORR)
Objective Response Rate (ORR) is defined as the percentage of participants, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria, during the study treatment. The determination of clinical response will be based on investigator reported measurements. Responses will be evaluated every 8 weeks.
Time frame: 24 months
Progression-free survival (PFS)
Progression-free survival (PFS) is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first. PFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of progressive disease for participants who are alive, on study and progression free at the time of the analysis. Alive participants who have no tumor assessments after baseline will have time to event censored on the date of randomization.
Time frame: 24 months
Overall Toxicity Rate
Overall Toxicity Rate is defined as the percentage of participants, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during the treatment.
Time frame: 24 months
Toxicity Rate
Toxicity Rate is defined as the percentage of participants, relative to the total of enrolled subjects, experiencing a specific adverse event of grade 3 - 4, according to National Cancer Institute Common Toxicity Criteria (version 5.0)3, during the treatment.
Time frame: 24 months
Quality of Life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
The EORTC QLQ-C30 contains functional scales, symptom scales, single items scale and a global health status/QoL scale. Raw scores are standardized and converted into scale scores ranging from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales.
Time frame: Questionnaires will be administered at baseline, 8 weeks, 16 weeks, 12- and 24-months post-randomisation.
Quality of Life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Module for Colorectal cancer 29 (EORTC QLQ-CR29).
The EORTC QLQ-CR29 includes 29 items that evaluate symptoms (gastrointestinal, urinary, pain and others) and functional areas (sexual, body image and others) that are associated with CRC and its treatments. There are separate items for patients with and without a stoma and separate items to evaluate the sexual function of men and women. Raw scores are standardized and converted into scale scores ranging from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales.
Time frame: Questionnaires will be administered at baseline, 8 weeks, 16 weeks, 12- and 24- months post-randomisation.
Quality of Life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life - Additional items to cover anti-EGFR (IL126)
The EORTC IL126 includes 20 items that evaluate additional items to cover anti-EGFR symptomatic toxicity. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales.
Time frame: Questionnaires will be administered at baseline, 8 weeks, 16 weeks, 12- and 24- months post-randomisation.
Quality of Life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life EQ-5D-3L (3-level version of EQ-5D by the EuroQol Group)
The EQ-5D-3L consists of: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'.
Time frame: Questionnaires will be administered at baseline, 8 weeks, 16 weeks, 12- and 24- months post-randomisation.
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Plan to share: No
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