A Randomized Phase III Trial Comparing Folfirinox to Gemcitabine in Locally Advanced Pancreatic Carcinoma

Inclusion Criteria: 1. Histologically or cytologically confirmed adenocarcinoma of the pancreas 2. Proven unresectability after multidisciplinary discussion involving radiologist and a surgeon 3. Locally advanced (i.e.: no metastasis or suspicion of metastasis) and unresectable tumors: for example mesenteric or portal vein involvement, or \> 180° encasement of the superior mesenteric artery, or celiac abutment (NCCN 2012 criteria) 4. Measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according RECIST 1.1 5. WHO Performance status (PS) 0-1 6. Age ≥18 years 7. Patient with organ function as follows: * Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L * Hemoglobin ≥ 10 g/dL * Platelets (PTL) ≥ 75 x 10⁹/L * Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) * Bilirubin ≤ 1.5 x ULN * Creatinine ≤ 2 x ULN * Albumin \> 0.75 x lower limit of normal (LLN) * Urea ≤ 2 x ULN 8. Adequate vital functions 9. Patient of child-bearing potential (for female patient: study entry after a menstrual period and a negative pregnancy test) must agree to use medically acceptable methods of contraception during the study and for 4 months after the last intake of study treatment for women and for 6 months after for men. 10. Patient information and signed informed consent form 11. Public or private health insurance coverage 12. Uracilemia \< 16 ng/ml Exclusion Criteria: 1. Patient treated for a cancer other than pancreatic cancer within 5 years before enrolment, with the exception of basal cell carcinoma or in situ cervical cancer 2. Patient with metastasis or with history of metastasis 3. Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e. congestive heart failure, myocardial infarction within 6 months before baseline) 4. Major comorbidity, active infection (HIV or chronic hepatitis B or C) or uncontrolled diabetes that may preclude the delivery of the treatment 5. Pre-existing neuropathy (Grade ≥ 2), Gilbert's disease or genotype UGT1A1 \* 28 / \* 28 6. Pregnant woman 7. Fructose intolerance 8. Patients currently treated by warfarin 9. Persons deprived of liberty or under guardianship 10. Psychological condition, family-, sociological- or geographical situation potentially hampering compliance with the study protocol and the follow-up schedule