Conversion Therapy of RAS/BRAF Wild-Type Colorectal Cancer Patients With Initially Unresectable Liver Metastases

Patients will be stratified for primary tumor location (right-sided or left sided) and numbers of liver metastases (\<5 or ≥5). Patients with RAS/BRAF wild-type primary tumors will be randomized between mFOLFOXIRI plus cetuximab (cetuximab 500 mg/m\^2 in 60 minutes i.v., followed by oxaliplatin 85 mg/m\^2 i.v. in 120 minutes, followed by irinotecan 165 mg/m\^2 i.v. in 60 minutes, together with leucovorin 400 mg/m\^2 i.v. in 120 minutes, followed by continuous infusion of 5-fluorouracil 2400 mg/m\^2 in 46 hours, every 2 weeks) or mFOLFOXIRI plus bevacizumab (Bevacizumab 5 mg/kg in 15-30 minutes i.v., followed by oxaliplatin 85 mg/m\^2 i.v. in 120 minutes, followed by irinotecan 165 mg/m\^2 i.v. in 60 minutes, together with leucovorin 400 mg/m\^2 i.v. in 120 minutes, followed by continuous infusion of 5-fluorouracil 2400 mg/m\^2 in 46 hours, every 2 weeks). Patients will be evaluated every 8 weeks by MRI or CT scan for disease status. The assigned systemic treatment should be continued for at least 6 months or earlier in case of resectability, progression of disease, unacceptable toxicity, or patient refusal. If after 6 months MDT concludes that the patient is still not resectable, it is highly unlikely that resectability will be achieved at all. Therefore the chemotherapy regimen may be reconsidered after 6 months of treatment. In patients who will become resectable and undergo secondary surgery of liver metastases, the total duration of preoperative and postoperative treatment together should be 6 months. However, the postoperative chemotherapy regimen was determined by the investigator. After 70% of patients were enrolled and conversion therapy were finished, a mid-term analysis will be performed.