Cetuximab as Salvage Therapy in Patients With Neo Wild-type RAS/RAF Metastatic Colorectal Cancer With Liver Metastases.

Inclusion Criteria:

1. Provision of signed and dated informed consent and stated willingness to comply with all study procedures and availability for the duration of the study,
2. Male or female subjects, ≥18 years of age,
3. ECOG performance status (ECOG PS, Appendix 15.1) ≤2,
4. Unresectable metastatic RAS mutant (either KRAS or NRAS tumor gene mutation) colorectal cancer,
5. At least one (≥1) measurable and/or evaluable liver metastasis,
6. Prior therapy (resistant or intolerant) with fluoropyrimidines, oxaliplatin, irinotecan and antiangiogenic agent (ie, bevacizumab and/or aflibercept),
7. Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:

   Hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; haemoglobin ≥9g/dL Adequate renal function: serum creatinine clearance (MDRD) ≥ 50 mL/min/1,73 m2 Adequate liver function: serum bilirubin ≤1.5x upper normal limit (ULN), alkaline phosphatase \<5xULN, AST and ALT ≤5xULN, Adequate serum electrolyte levels (magnesium, potassium, calcium) prior to initiation of study treatment,
8. Negative pregnancy test within 7 days prior to initiation of the study drug for female patients of childbearing potential,
9. Effective contraception for both male and female subjects if the risk of conception exists
10. Registration in a national health care system.

Exclusion Criteria:

1. Known allergy or hypersensitivity reactions to any study drug,
2. Women who are pregnant or breastfeeding,
3. Inability to comply with study and follow-up procedures as judged by the Investigator,
4. Patient with BRAF mutant colorectal cancer
5. History of interstitial lung disease
6. Treatment with strong CYP3A4-enzyme inducers such as anticonvulsants (phenytoin, phenobarbital or carbamazepine), rifampin, rifabutin and St. John's wort for patients of cohort #2
7. Treatment with strong CYP3A4-enzyme inhibitors (e.g. grapefruit juice, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) for patients of cohort #2
8. Treatment with strong UGT1A inhibitors (e.g. atazanavir, gemfibrozil, indinavir) for patients of cohort # 2
9. Patients of cohort #2 with known UGT1A deficiency
10. Uncontrolled illness, including but not limited to ongoing bacterial, viral or fungal infection requiring systemic therapy, metabolic dysfunction, physical examination/ clinical laboratory finding that leads to a reasonable suspicion of a disease/condition that contraindicates the use of any of investigational drugs that may affect the interpretation of the results, or that may render the subject at high risk of treatment complications.
11. Patient with current intestinal obstruction or history of chronic inflammatory bowel disease
12. Subjects under guardianship, curatorship or judicial protection