A Randomized Phase III Study Comparing Maintenance Treatment With Fluoropyrimidine + Bevacizumab Versus Fluoropyrimidine After Induction Chemotherapy for a Metastatic Colorectal Cancer

The aim of BEVAMAINT is to improve benefic effect of maintenance therapy after a first line of induction chemotherapy for patients with colorectal cancer

Inclusion Criteria: * Histologically confirmed metastatic colorectal adenocarcinoma before induction treatment * Measurable or non-measurable lesion before the induction treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) * Metastatic, unresectable disease according local practice after induction treatment * ECOG performance status ≤ 2 * Disease control (complete response, partial response or stable disease) after 4-6 months of frontline induction chemotherapy with doublet (fluoropyrimidine + irinotecan or oxaliplatin) or triplet (fluoropyrimidine + irinotecan + oxaliplatin) +/- (cetuximab, panitumumab, bevacizumab) or IAH chemotherapy * Life expectancy \> 3 months * Age ≥ 18 years * Patient is at least 4 weeks from any major surgery * Total bilirubin \< 25 µmol/L, ASAT \< 3 x ULN, ALAT \< 3 x ULN (ASAT , ALAT \< 5 x ULN in case of hepatic metastasis) , PT \>60% , PAL\ 1500/mm3, platelets \> 100 000/mm3, haemoglobin ≥ 9 g/dL * Creatinin clearance \> 30 ml/min (MDRD) - if creatinin clearance comprised between 30 and 50 ml/min, see smPCs for dose adjustments * Proteinuria ≤ 2+ (dipstick urinalysis) (if more than 2+, so proteinuria at or ≤1g/24hour must be ≤1g) * Patient is able to understand, sign, and date the written informed consent * Evidence of post-menopausal status or negative urinary or serum pregnancy test for premenopausal female patients * Male and female patients of childbearing potential agree to use a highly effective contraceptive measure * Patient affiliated to a social security system Exclusion Criteria: * Myocardial infarction, severe coronaropathy or severe cardiac dysfunction less than 6 months prior randomization * Follow-up impossible * Patients with all metastases resected (R0/R1) after induction chemotherapy * Patient with a hand-foot syndrome \> 1 before maintenance treatment * Known brain or leptomeningeal metastases * Other concomitant or previous malignancy, except: adequately treated in situ carcinoma in complete remission for \> 5 years * Uncontrolled hypertension (defined as systolic blood pressure \>140 mmHg and/or diastolic blood pressure \>90 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy * Pregnancy or breast feeding * Treatment with sorivudine or analogs (brivudine) * Treatment with phenytoin or analogs * Partial or complete DPD deficiency (Uracilemia ≥ 16 ng/ml) * Peptic ulcer not healed after treatment * Any contraindication to bevacizumab or fluoropyrimidine treatments according to the updated SmPC * Intestinal perforation or intestinal fistula * Previous or active gastrointestinal bleeding * Thromboembolic event and/or history of thromboembolic event * Severe hepatic insufficiency