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

Comparative interventional prospective phase 3, randomized, open-label, multicentric trial comparing chemotherapy with Folfirinox to Gemcitabine in locally advanced pancreatic carcinoma.

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of the pancreas
• Proven unresectability after multidisciplinary discussion involving radiologist and a surgeon
• 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)
• Measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according RECIST 1.1
• WHO Performance status (PS) 0-1
• Age ≥18 years
• 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
• Adequate vital functions
• 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.
• Patient information and signed informed consent form
• Public or private health insurance coverage
• Uracilemia < 16 ng/ml

Exclusion criteria

• 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
• Patient with metastasis or with history of metastasis
• 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)
• Major comorbidity, active infection (HIV or chronic hepatitis B or C) or uncontrolled diabetes that may preclude the delivery of the treatment
• Pre-existing neuropathy (Grade ≥ 2), Gilbert's disease or genotype UGT1A1 * 28 / * 28
• Pregnant woman
• Fructose intolerance
• Patients currently treated by warfarin
• Persons deprived of liberty or under guardianship
• Psychological condition, family-, sociological- or geographical situation potentially hampering compliance with the study protocol and the follow-up schedule