Evaluation of the Efficacy and the Safety of FOLFIRINOX3 Bevacizumab Treatment in Patients With Colorectal Cancer (FOLFIRINOX 3)

Primary objective

• Main objective of phase I: To evaluate the acute toxicity of treatment with FOLFIRINOX 3 - bevacizumab
• Main objective of phase II: To evaluate the efficacy of treatment with FOLFIRINOX 3 - bevacizumab in terms of objective response according to the RECIST criteria.

Secondary objectives

• To evaluate the efficacy of treatment with FOLFIRINOX 3 - bevacizumab in terms of objective response according to the criteria of CHOI, progression-free survival (PFS) and overall survival (OS)
• To evaluate the late toxicity of treatment with FOLFIRINOX 3 - bevacizumab
• Evaluate the quality of life

Inclusion criteria

• Men or women
• Age ≥ 18 years
• Performance status of 0 or 1 (WHO ECOG Index)
• Patient with metastatic colon cancer
• History of chemotherapy treatment including oxaliplatin, irinotecan, antiangiogenic (bevacizumab or aflibercept) and anti-EGFR if indicated
• Patient eligible for treatment with FOLFIRINOX bevacizumab
• Tumor evaluation (thoraco-abdominopelvic CT scan) performed within 4 weeks before inclusion with at least one measurable lesion according to RECIST criteria 1.1
• Patient able and able to abide by the protocol throughout the study, including treatment, visits, scheduled examinations and follow-up.
• Biological values within the following limits:

• Bilirubinemia ≤ 1.5 times the upper limit of normal (N)
• ASAT and ALAT ≤ 5 N
• Creatinine ≤ 1.5 N and creatinine clearance> 60 mlmin
• Neutrophils ≥ 1.5. 109 / L
• Platelets ≥ 150. 109 / L
• Hemoglobin ≥ 9 g / dL (patients can be included even if they have been transfused).
• Albuminémie≥30g / L
• Hepatitis B, C and HIV negative serologies
• Information note given and signed informed consent
• Patient affiliated to a social security scheme
• Women must have effective contraception and must have a negative pregnancy test at the time of entry into the study or must no longer be of childbearing age (ie, postmenopausal, after 60 years and no menstruation for ≥1 year without any other medical cause, OR history of hysterectomy, OR history of bilateral oophorectomy),

Exclusion criteria

• Other cancer in the 5 years prior to entry into the trial or concomitant (except in situ cancer of the cervix or basal cell carcinoma of the skin).
• Presence of cerebral metastasis (s)
• Prognosis estimated <3 months
• Presence of a contraindication to bevacizumab (major surgery in the previous 28 days, risk of arterial thrombosis, risk of haemorrhage, deep vein thrombosis without effective anticoagulant therapy or unbalanced anticoagulant therapy)
• History of grade 4 toxicity to oxaliplatin, irinotecan, 5FU or bevacizumab
• Persistence of neuropathy greater than a grade 1
• Hypersensitivity to one of the compounds of the treatments
• Participation in course or within 30 days prior to entry into the study to another therapeutic trial with an experimental molecule.
• Demonstration of a DPYD and / or UGT1A1 mutation
• Unbalanced serious illness, underlying infection that may prevent the patient from receiving treatment
• Pregnancy (compulsory pregnancy test at baseline), breastfeeding or lack of effective contraception for men and women of childbearing age
• Psychiatric illness compromising understanding of information or completion of study
• Patient under tutorship, curatorship or court of justice
• Inability to sign informed consent or to undergo medical follow-up of the trial for geographical, social or psychological reasons.