Critères d'inclusion : 1. Signed and dated informed consent, and willing and able to comply with protocol requirements,
2. Histologically or cytologically proven adenocarcinoma of the pancreas,
3. In absence of histologically or cytologically proven adenocarcinoma, a cluster of clinical, biological and radiological arguments consistent with the diagnosis: among these, a hypodense pancreatic tumor at CT and a Ca 19-9 greater than 500 UI/ml are essential prerequisites,
4. Metastatic disease confirmed (stage IV),
5. No prior therapy for metastatic disease (in case of previous adjuvant therapy, interval from end of chemotherapy and relapse must be >12 months),
6. Age ≥18 years,
7. Patient non-fit for FOLFIRINOX, with ECOG performance status (PS) 0-2
8. For patients with ECOG performance status (PS) = 2, an albuminemia level >25 g/l is required. An albumin infusion is not permitted before the inclusion test,
9. Haematological status: neutrophils (ANC) >1.5x109/L; platelets >100x109/L; haemoglobin ≥9g/dL,
10. Adequate renal function: serum creatinine level <150μM,
11. Adequate liver function: AST (SGOT) and ALT (SGPT) ≤2.5xULN (≤5xULN in case of liver metastases),
12. Total bilirubin ≤3 x ULN,
13. Baseline evaluations performed before randomization: clinical and blood evaluations no more than 2 weeks (14 days) prior to randomization, tumor assessment (CT-scan or MRI, evaluation of non-measurable lesions) no more than 3 weeks (21 days) prior to randomization,
14. Female patients must be surgically sterile, or be postmenopausal, or must commit to using reliable and appropriate methods of contraception during the study and during at least six months after the end of study treatment (when applicable). All female patients with reproductive potential must have a negative pregnancy test (β HCG) within 7 days prior to starting protocol treatment. Breastfeeding is not allowed.
15. Male patients must agree to use effective contraception in addition to having their partner use a contraceptive method as well during the trial and during at least six months after the end of the study treatment,
16. Affiliation to a French social security system (recipient or assign).
Critères de non-inclusion : 1. History or evidence upon physical examination of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy),
2. Local or locally advanced disease (stage I to III),
3. Patient uses warfarin,
4. Patient receiving concomitant radiotherapy,
5. Uncontrolled hypercalcemia,
6. Pre-existing permanent neuropathy (NCI grade ≥2),
7. Poor nutritional status
8. Known dihydropyrimidine dehydrogenase (DPD) deficiency,
9. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
10. Treatment with any other investigational medicinal product within 28 days prior to study entry,
11. Other serious and uncontrolled non-malignant disease (eg. active infection requiring systemic therapy, coronary stenting or myocardial infarction or stroke in the past 6 months),
12. Known or historical active infection with HIV, or known active infection untreated with hepatitis B or hepatitis C,
13. Known uncontrolled bacterial infection
14. History or active interstitial lung disease (ILD),
15. Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years,
16. Patients with known allergy to active substance or any excipient of study drugs,
17. Allergy to iodinated contrast product
18. Concomitant administration of live, attenuated virus vaccine such as yellow fever vaccine and concomitant administration of prophylactic phenytoin
19. Patients under legal protection or unable to consent
20. Participation in another interventional research