FOLFOXIRI Plus Panitumumab In Kras and Braf Wild-Type Metastatic Colorectal Cancer

Inclusion Criteria: * Histologically confirmed colorectal adenocarcinoma; * Availability of formalin-fixed paraffin embedded tumor block from primary or metastasis; * KRAS and BRAF wild-type status of primary colorectal cancer or related metastasis; * Unresectable and measurable metastatic disease according to RECIST criteria; * Male or female, aged \>/= 18 years and \</= 75 years; * ECOG PS \< 2 if aged \< 71 years; * ECOG PS = 0 if aged 71-75 years; * Life expectancy of more than 3 months; * Adequate haematological function: ANC ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, Hb ≥ 9 g/dL; * Adequate liver function: serum bilirubin ≤ 1.5 x ULN; alkaline phosphatase and transaminases ≤ 2.5 x ULN (in case of liver metastases \< 5 x ULN); * Serum creatinine ≤ 1.5 x ULN; * Previous adjuvant chemotherapy is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse; * At least 6 weeks from prior radiotherapy and 4 weeks from surgery; * Written informed consent to experimental treatment and pharmacogenomic analyses; * Magnesium ≥ lower limit of normal; * Calcium ≥ lower limit of normal. Exclusion Criteria: * Prior palliative chemotherapy; * Prior treatment with EGFR inhibitors; * Symptomatic peripheral neuropathy ≥ 2 grade NCIC-CTG criteria; * Presence or history of CNS metastasis; * Active uncontrolled infections; active disseminated intravascular coagulation; * Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix; * Clinically significant cardiovascular disease, for example cerebrovascular accidents (CVA) (≤ 6 months before treatment start), myocardial infarction (≤ 6 months before treatment start), unstable angina, NYHA ≥ grade 2 chronic heart failure (CHF), uncontrolled arrhythmia; * Fertile women (\< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception; * Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment; * History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.