Detection of the Emergence of RAS (Rat Sarcoma Viral Oncogene Homolog) Mutations in Circulating DNA (Deoxyribonucleic Acid) in Patients With mCRC (Metastatic Colorectal Cancer) During Treatment With Anti-EGFR (Epidermal Growth Factor Receptor) Therapy

Study Overview
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Brief Summary
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The analysis of circulating DNA (Deoxyribonucleic acid) to identify potential resistance mechanisms during anti-EGFR (epidermal growth factor receptor) treatment is of great interest, as evidenced by the recent journal published by Corcoran in the prestigious New England Journal of Medicine. EmutRAS is one of the first studies that will specifically and prospectively evaluate the RAS mutational switch and its impact on the efficiency of the 1st line processing.

Detailed Description
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The primary study objective is the Detection of RAS mutational (rat sarcoma viral oncogene homolog) switch in circulating DNA by Intplex® test in mCRC (metastatic colorectal cancer) patients treated with antibody anti-EGFR (epidermal growth factor receptor), cetuximab or panitumumab in first line. The treatment and these modalities will be decided by the investigator. The study is based on blood sampling, the frequency of which is described below, rhythm of plasma samples: Inclusion after determination of wild status RAS tissues. First sampling of 2 EDTA (ethylenediaminetetraacetic acid) tubes, then at each tumour evaluation during treatment with anti EGFR (epidermal growth facor receptor), every 4 cures. At the end of treatment or after more than 36 treatment cures, a final sample will be taken. No results of the samples will be communicated to the investigator, the sponsor will centralize these results for the final analysis of the study.

Official Title
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Detection of the Emergence of RAS (Rat Sarcoma Viral Oncogene Homolog) Mutations in Circulating DNA (Deoxyribonucleic Acid) in Patients With Metastatic Colorectal Cancer During Treatment With Anti-EGFR (Epidermal Growth Factor Receptor) Therapy

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Device: Intplex test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with histologically confirmed metastatic colorectal cancer Patient treated in the first line by one of the treatments below and according to a bi-monthly schema for cetuximab: FOLFIRI (elvorin + 5 Fluorouracil + irinotecan) ou FOLFOX (elvorin + 5 Fluorouracil + oxalplatin) + Cetuximab* (Erbitux) ; FOLFIRI ou FOLFOX + Panitumumab (Vectibix); FOLFIRINOX ou FOLFOXIRI ((elvorin + 5 Fluorouracil + oxaliplatin + irinotecan) + Cetuximab* (Erbitux); FOLFIRINOX ou FOLFOXIRI + Panitumumab (Vectibix) For patient treated cetuximab administration will be bi-monthly Patient with at least one evaluable metastatic target according to RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) Wild RAS (rat sarcoma viral oncogene homolog) status detected by standard tissue test, on primary tumor and / or metastasis Wild BRAF (murine sarcoma viral oncogene homolog B) status detected by standard tissue test, on primary tumor and / or metastasis Man or woman> 18 years old Signed informed consent before any specific procedure to study Patient affiliated to the social security or equivalent Exclusion Criteria: Previous treatment with an anti-EGFR (epidermal growth factor receptor) Patient with a multifocal primary tumor RAS (rat sarcoma viral oncogene homolog) status mutated or not detectable on tissue analysis BRAF (murine sarcoma viral oncogene homolog B) status mutated or undetectable on tissue analysis Patient receiving adjuvant chemotherapy or radiotherapy within <14 days History of other cancer in the last 5 years (except in-situ carcinoma of the cervix and cutaneous carcinoma excluding melanoma treated optimally) Blood transfusion (whole blood, red blood cell, platelets...) in the previous week Patients with psychological, familial, sociological or geographic conditions potentially not favorable to the good observance of the study protocol and the follow-up Legal incapacity or limited legal capacity Participation in another interventional clinical trial - biomedical research (therapeutic strategy type) is not excluded provided that it is use an Anti-EGFR with a AMM (marketing authorization), (Cetuximab - Panitumumab) with a dose and a standard administration rhythm (according to the AMM).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intplex test<br>In vitro diagnostic device | Device: Intplex test<br>* Blood sample at each tumor assessment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with mCRC (metastatic colorectal cancer) who develop a RAS (rat sarcoma viral oncogene homolog) mutation under anti-EGFR (epidermal growth factor receptor) therapy | From baseline to the end of treatment | Approximately 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability of obtaining a positive test, i.e. RAS status mutated by the Intplex® test, among the patients determined RAS mutated by the tissue test | From baseline to the end of treatment | Approximately 8 weeks | 
| Probability of obtaining a negative test, i.e. wild RAS status by the Intplex® test among patients determined wild RAS by the tissue test | From baseline to the end of treatment | Approximately 8 weeks | 
| Probability of obtaining a positive test, i.e. BRAF status mutated by the Intplex® test, among the patients determined BRAF mutated by the tissue test | From baseline to the end of treatment | Approximately 8 weeks | 
| Probability of obtaining a negative test, i.e. wild BRAF status by Intplex® test among patients determined wild BRAF by tissue test.compared to the pre-treatment tissue test | From baseline to the end of treatment | Approximately 8 weeks | 
| Proportion of patients with a BRAF mutation under anti-EGFR therapy | From baseline to the end of treatment | Approximately 8 weeks | 
| Progression-free survival | From baseline to the database cutoff | Approximately 36 months | 
| Global survival | From baseline to the database cutoff | Approximately 36 months | 
| Evaluation of the following criterion: total concentration of circulating DNA | From baseline to the end of treatment | Approximately 8 weeks | 
| Evaluation of the following criterion: integrity index | From baseline to the end of treatment | Approximately 8 weeks | 
| Evaluation of the following criterion: concentration of mutated alleles | From baseline to the end of treatment | Approximately 8 weeks | 
| Evaluation of the following criterion: frequency of mutated alleles | From baseline to the end of treatment | Approximately 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Detection of the emergence of RAS mutations, Treatment with anti-EGFR therapy, Metastatic Colorectal Cancer, Circulating DNA in patients