Sorafenib in Combination With Irinotecan in Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors

Inclusion Criteria: * Male or female ≥ 18 years old * Histologically confirmed diagnosis of colorectal cancer * Asymptomatic or resected primary tumor * Metastatic colorectal cancer patient not eligible for curative surgery * At least one target lesion: * Unidimensionally measurable on cross-sectional imaging * In an area not previously irradiated * Disease progression after failure of active drugs (5-Fu or 5-Fu prodrugs, irinotecan, oxaliplatin, bevacizumab) * Patients with bone metastases are eligible if they have other measurable lesions * WHO performance status ≤ 2 * Confirmation of KRAS mutation in codons 12 or 13 in the primary tumor or metastases * Total bilirubin ≤ 1.5 ULN, ALT or AST ≤ 2.5 ULN (or \< 5 in case of liver impairment) * Haemoglobin ≥ 10 g/dL, neutrophils ≥ 1,500/mm3, platelets ≥ 100,000/mm3 * Serum creatinine ≤ 1.5 ULN * Negative pregnancy test in women of childbearing potential * Use of an effective contraceptive method during the whole treatment and up to 3 months after the completion of treatment in males and females * Life expectancy of at least 3 months * Informed consent signed prior any study specific procedures * Tumor evaluation should be performed within 3 weeks prior to starting treatment Exclusion Criteria: * History of Gilbert's syndrome * Symptomatic brain metastases or carcinomatous meningitis * Bone-only metastases * History or presence of other cancers within the past 5 years (except curatively treated non-melanoma skin cancer and in situ cervical cancer) * Prior surgery or radiotherapy within 4 weeks before entering the study * Cardiac arrhythmia requiring treatment (except for beta-blockers and digoxin), unstable cardiac disease, myocardial infarction within the previous 6 months, \> grade II NYHA heart failure, uncontrolled hypertension * Kalemia lower than normal serum potassium value * From ECG, QTc interval \> 470 ms * History of acute or chronic pancreatitis * History of epileptic seizures requiring long-term anticonvulsant therapy * History of organ transplantation with use of immunosuppression therapy * Severe bacterial or fungal infection (Grade \> 2 NCI-CTCAE v.4.0) * Known HIV infection * Long-term use of CYP 3A4 enzyme-inducing agents such as rifampicin, St. John's Wort (hypericum perforatum), phenytoin, carbamazepine, phenobarbital, dexamethasone, and ketoconazole * Pregnant or breastfeeding women * Bowel malabsorption or extended bowel resection that could affect the absorption of sorafenib, occlusive syndrome, inability to take oral medications * Inflammatory bowel disease with chronic diarrhea (NCI-CTCAE v.4.0) * Participation in another clinical trial 30 days prior to study entry * Concurrent treatment with any other investigational product or anticancer therapy (except for irinotecan or sorafenib) * Psychological, social, geographical disorders or any other condition that would preclude study compliance (treatment administration and study follow-up).