First Line Metastatic Pancreatic Cancer : 5FU/LV+Nal-IRI, Gemcitabine+Nab-paclitaxel or a Sequential Regimen of 2 Months 5FU/LV+Nal-IRI

Prior treatment

• Prior radiation therapy (except if there is at least one measurable target outside irradiation area)
• History of any second malignancy in the last 5 years; subjects with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they had been continuously disease free for at least 5 years.
• Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before inclusion.
• Use of CYP3A4/UGT1A inducers/inhibitors
• Use of strong CYP2C8 inhibitors or inducers, or presence of any other contraindications for nab-paclitaxel or gemcitabine

Other illness

• Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea \> Grade 1
• History of chronic inflammatory bowel disease
• Gilbert's syndrome
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure.
• Known hypersensitivity to any of the drugs /constituents or non-liposomal irinotecan
• Any other medical or social condition deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.

Other

• Uncontrolled brain or meningeal metastasis, or bone metastasis (no need of systematic CT scan)
• Other types of pancreatic tumours, in particular endocrine or acinar cell tumours
• Ampulloma
• Presence of neuropathy \> grade 1 according to NCI-CTC
• ILD presence
• Pregnant or breast feeding

• Histopathologically or cytologically proven pancreatic adenocarcinoma (on primitive or metastatic lesion)
• Metastatic disease at a distance
• At least one measurable lesion according RECIST v1.1 criteria
• 18 ≤ age ≤ 75 years
• Life expectancy \>12 weeks
• Performance status WHO \< 2
• No prior chemotherapy : adjuvant chemotherapy by gemcitabine +/- capecitabine is allowed if ended at least 12 months before the inclusion and adjuvant or neo-adjuvant FOLRIFINOX chemotherapy is allowed if ended at least 12 months prior the inclusion
• Pain well controlled before the inclusion of the patient
• ANC ≥ 1,500 cells/μL (without the use of hematopoietic growth factors); platelet count ≥ 100,000 cells/μL, hemoglobin ≥ 9 g/dL (blood transfusions is permitted for patients with hemoglobin levels below 9 g/dL)
• Adequate hepatic function as evidenced by: Serum total bilirubin within normal range for the institution (Serum bilirubin ≤ 1,5 UNL) Biliary drainage allowed for biliary obstruction.
• Albumin levels ≥ 3.0 g/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN acceptable if liver metastases were present)
• Normal renal function test (creatinine clearance ≥ 50 ml/min)
• Normal ECG or ECG without any clinically significant findings
• Patient able to understand and sign an informed consent
• Females of child-bearing potential are required to test negative for pregnancy at the time of enrollment based on a urine or serum pregnancy test.
• Both male and female patients of reproductive potential were required to agree to use a reliable method of birth control, during the study and for 3 months following the last dose of study drug.
• Patient affiliated to social security
• Regular follow-up possible