Efficacy of FOLFOX Versus FOLFOX Plus Aflibercept in K-ras Mutant Patients With Resectable Liver Metastases

Inclusion Criteria: * Histologically proven CRC with 1 to 8 metachronous or synchronous liver metastases considered to be completely resectable * Primary tumor (or liver metastasis) of CRC must be KRAS status "mutant" * Patients must have undergone complete resection (R0) of the primary tumor at least 4 weeks before randomization. Or for patients with synchronous metastases the primary tumor can be resected (R0) at the same time as the liver metastases if: the patient has a non-obstructive primary tumor and is able to receive preoperative chemotherapy (3-4 months) before surgery1. * Measurable hepatic disease by RECIST version 1.1 * Patients must be 18 years old or older * A World Health Organization (WHO) performance status of 0 or 1 * Previous adjuvant chemotherapy for primary CRC is allowed if completed at least 12 months before inclusion in this study * All the following tests should be done within 4 weeks prior to randomization: * Hematological status: neutrophils (ANC) = 1.5x10 9/L; platelets = 100x10 9/L; haemoglobin = 9g/dL * Serum creatinine = 1.5 times the upper limit of normal (ULN) * Proteinuria \< 2+ (dipstick urinalysis) or =1g/24hour. * Liver function: serum bilirubin = 1.5 x upper normal limit (ULN), alkaline phosphatase \< 5xULN * Magnesium ≥ lower limit of normal (LLN) * Patients with a buffer range from the normal values of +/- 5% for hematology and +/- 10% for biochemistry are acceptable. This will not apply for Renal Function, including Creatinine. * Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 14 days prior to the first dose of study treatment. * Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. * Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment. * Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial * Patient should be willing and able to comply with protocol requirements * Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. Exclusion Criteria: * Evidence of extra-hepatic metastasis (of CRC) * Previous chemotherapy for metastatic disease or surgical treatment (e.g. surgical resection or radiofrequency ablation) for liver metastasis. Radiotherapy alone is allowed if given pre or post protocol treatment * Previous exposure to VEGF/VEGFR targeting therapy within the last 12 months * Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to randomization * Gilbert's syndrome * History of myocardial infarction and/or stroke within 6 months prior to randomization * Uncontrolled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \> 100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy * History or evidence upon physical examination of CNS metastasis * Bowel obstruction * Uncontrolled hypercalcemia * Pre-existing permanent neuropathy (NCI grade = 2) * Known allergy to any excipient to study drugs