FOLFOX + Panitumumab According to a "Stop and go" Strategy With a Reintroduction Loop After Progression on Fluoropyrimidine as Maintenance Treatment, as the First Line in Patients With Metastatic Colorectal Adenocarcinoma Without a RAS Mutation

Inclusion Criteria:

* \- Histologically proven colorectal adenocarcinoma without RAS mutation
* Confirmed, non-resectable metastatic disease (Stage IV)
* No prior chemotherapy except perioperative or adjuvant chemotherapy discontinued for more than 12 months
* At least one measurable metastasis according to the RECIST v1.1 criteria
* Age ≥ 18 years
* WHO ≤ 2
* Neutrophils \> 1500 /mm3, platelets\> 100 000/mm3, Hb \> 9 g/dL
* Creatinine clearance \> 50 mL/min according to the MDRD formula
* Serum bilirubin \< 25 µmol/L, AST, ALT, Alk Phos \< 2.5 x ULN or \< 5 x ULN in case of liver metastases
* PT \> 60%, albumin ≥ 25g/L
* Estimated life expectancy ≥ 3 months
* Patient affiliated to a social security scheme
* Patient informed and informed consent form signed

Exclusion Criteria:

* \- Presence of uncontrolled symptomatic brain metastases
* RAS mutation (KRAS or NRAS mutation)
* Patient taking warfarin. If treated with anticoagulant at the indicated effective dose, this must be replaced with low molecular weight heparin before inclusion
* Known DPD deficiency
* Peripheral neuropathy \> 1 (NCI CTCAE v4.0)
* Patient with interstitial pneumonitis or pulmonary fibrosis
* History of chronic diarrhoea or inflammatory disease of the colon or rectum, or obstruction or sub-obstruction during symptomatic treatment
* Poorly controlled chronic skin disease
* Any known specific contraindication or allergy to the medicinal products used in the study
* Patient simultaneously included in another clinical trial involving an investigational drug (example: chemotherapy, targeted therapy, immunotherapy)
* Arterial hypertension not controlled by medical treatment (Systolic BP ≥ 160 mmHg end/or diastolic BP ≥ 90 mmHg)
* Any progressive pathology not stabilised over the past 6 months: hepatic failure, renal failure, respiratory failure
* The following conditions in the 6 months prior to inclusion: myocardial infarction, severe/unstable angina, coronary artery bypass surgery, congestive heart failure NYHA class II, III or IV, stroke or transient ischaemic attack
* Patient who has received a transplant, is seropositive for HIV, hepatitis B or hepatitis C or has other immunodeficiency syndromes
* History of malignant pathologies during the past 5 years except basal cell carcinoma of the skin or cervical carcinoma in situ, properly treated
* QT/QTc interval \> 450 msec for men and \> 470 msec for women
* K+ \< LNL, Mg2+ \< LNL, Ca2+ \< LNL
* Lack of effective contraception in patients (men and/or women) of childbearing age, pregnant or breastfeeding women, women of childbearing age who have not had a pregnancy test
* Persons in custody or under wardship
* Impossibility of undergoing medical monitoring during the trial for geographical, social or psychological reasons