mFOLFOXIRI Plus Bevacizumab Versus mFOLFOX6 Plus Bevacizumab for the First Line Treatment of RAS Mutant Unresectable Colorectal Liver-limited Metastases
Colorectal cancer patients with initially unresectable liver-only metastases may be cured after downsizing of metastases by conversion therapy. However, the optimal regimen of conversion therapy for RAS mutant patients has not been defined. In this study colorectal cancer patients with initially unresectable liver-only metastases, as prospectively confirmed by a local multidisciplinary team (MDT) according to predefined criteria, will be tested for RAS and BRAF tumor mutation status. Patients with RAS mutant and BRAF wild type will be randomised between modified FOLFOXIRI (mFOLFOXIRI) plus bevacizumab and modified FOLFOX6 (mFOLFOX6) plus bevacizumab. Patient imaging will be reviewed for resectability by MDT, consisting of at least one radiologist and three liver surgeons every assessment. MDT review will be performed prior to randomization as well as during treatment, as described in the protocol.
• Histological proof of colorectal adenocarcinoma;
• Age ≥ 18 years and ≤75 years;
• Simultaneous liver-limited metastases;
• Initially unresectable liver metastases determined by a local MDT;
• RAS mutation and BRAF V600E wild-type;
• At least one measurable liver metastasis;
• Initially resectable primary tumor or primary tumor already resected;
• World Health Organization (WHO) performance status 0-1;
• Life expectancy ≥ 3 months;
• Adequate hematologic function: absolute neutrophil count (ANC)≥1.5×109/l, platelets≥100×109/l, and hemoglobin(HB) ≥ 9g/dl;
• Adequate liver and renal function: total bilirubin ≤2.0 mg/dl, serum transaminases ≤ 5x upper limit of normal(ULN), and serum creatinine ≤ 1.5x ULN and creatinine clearance ≥ 30 ml/min;
• Written informed consent.