Chemotherapies Associated With Targeted Therapies on the Resection Rate of Hepatic Metastases

Inclusion criteria

• Histologically proven colorectal adenocarcinoma,
• Primary tumor of the colon or rectum, resectable or resected at least 3 weeks before randomization or 4 weeks before the beginning of the study treatment,
• Metastatic disease with synchronous or metachronous (> 3 months after diagnosis of the primary tumor) hepatic metastasis,
• Non-resectable (with respect to curative intent) hepatic metastasis at presentation. This criterion must be validated by both a surgeon and a radiologist during the RCP (Multidisciplinary cancer case presentation committee) patient's evaluation meeting (either technically non-resectable metastases (absolute contraindication): i.e. impossibility to resect all metastases in a single operation while preserving at least 30% of healthy liver tissues and/or impossibility to preserve the portal vein and hepatic artery homolateral to the liver or a portal pedicle, or due to oncological non-resectability (relative contraindication): presence of > 5 nodules and bilateral invasion),
• Hepatic metastases, without spread to other sites except in case of ≤ 3 resectable pulmonary metastases of diameter < 2 cm, detected by thoracic scanner,
• K-Ras status determined before randomization,
• Measurable disease according to the RECIST V1.1 criteria,
• No prior treatment of the hepatic metastases,
• Previous 5FU +/- oxaliplatin-based adjuvant chemotherapy administered after colorectal tumor resection is authorized if complete more than 1 year before,
• Age ≥ 18 & ≤ 75 years
• Performance status : ECOG 0 or 1,
• Life expectancy ≥ 3 months,
• Hemoglobin ≥ 9 g/dl,
• Polynuclear neutrophiles ≥ 1500/mm3,
• Platelets ≥ 100 000 mm3,
• Creatinemia ≤ 135 µmol/l (1,35 mg/dl)
• Total bilirubin ≤ 1.25 times the Upper Limit of Normal (ULN).
• Hepatic enzymes ASAT and ALAT < 5 x ULN,
• Negative pregnancy test for women of child-bearing age,
• Information given to the patient and signed informed consent,
• Public Health insurance coverage.

Exclusion criteria

• Non metastatic and/or non measurable disease according to the RECIST v1.1 criteria.
• Non-resectable primary tumor (e.g.: T4 tumors) or incomplete resection R2.
• History of intestinal inflammatory disease.
• Specific contraindication to any of the study treatments.
• Patient who have previously received anti-EGFr (e.g., cetuximab) or anti-VEGF monoclonal antibody treatment (e.g., bevacizumab) or treatment with irinotecan.
• History of cancer considered as not cured.
• Stroke/CVA or pulmonary embolism within 6 months before inclusion.
• Significant concomitant disease such as: coagulopathy, respiratory or cardiac congestive insufficiency, non-medically controlled/unstable angina pectoris, myocardial infarction within 6 months prior to study entry, arterial hypertension and uncontrolled arrhythmia, severe infections.
• Clinical neuropathy, grade ≥1.
• Patient already included in another therapeutic trial using an experimental molecule.
• Pregnant women or women who might become pregnant during the study or lactating women.
• Men or women who can procreate and who do not abide with the use of a contraceptive means.
• Persons kept in detention or incapable of giving consent
• Patient unwilling or unable to comply with the medical follow-up required by the trial because of geographic social or psychological reasons.