• Patient aged from 18 to 75 years at the date of signature of the consent form

• Histologically or cytologically proven pancreatic adenocarcinoma

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

• Non-resectable tumour according to the National Comprehensive Cancer Network (NCCN) 1.2015 recommendations after external review of imaging data by multidisciplinary experts.

• Non-metastatic cancer confirmed by thorax-abdomen-pelvis computerized tomography (CT) scan and liver MRI

• SMART feasibility confirmed by centralized review

• Uracilemia \< 16 ng/ml

• Hematological assessment within 14 days before inclusion, defined by:

‣ Neutrophils ≥ 2 000/mm3 (2 × 109/L);

⁃ Platelets ≥ 100 000/mm3 (100 × 109/L);

⁃ Hemoglobin ≥ 9 g/dl

• Liver function (within 14 days before inclusion) defined by:

‣ ASpartate Transaminase (AST) and ALanine Transaminase (ALT) ≤ 2.5 x Upper Limit of Normal (ULN);

⁃ Total bilirubin ≤ 1.5 x ULN. Patients with a metallic biliary prosthesis due to biliary obstruction caused by the cancer may be included, if: a CT scan with injection of contrast medium and thin pancreas sections was performed before placing the biliary prosthesis, the bilirubin level after prosthesis fitting decreased to ≤20 mg/L (≤34 μmol/L), and in the absence of cholangitis.

⁃ Creatininaemia within the reference limits, or calculated clearance ≥50 ml/min for patients with a serum creatinine value above or below the reference values (clearance calculated using the Chronic Kidney Disease EPIdemiology collaboration (CKDEPI formula).

⁃ Serum calcium AND magnesium AND potassium ≥ Lower Limit Normal (LLN and ≤ 1.2 x Upper Limit Normal (ULN)

⁃ Cancer Antigen (CA 19.9) \<500 IU/mL (without cholestasis). Patients with CA 19.9 between 500 IU/mL and 1000 IU/mL can be included if the Positron Emission Tomography (PET) scan and peritoneal MRI (optional) do not detect any distant fixation, indicative of metastasis. Patients with CA 19.9 ≥ 1000 IU/mL cannot be included.

⁃ Sexually active patients must use a contraceptive method considered adequate and suitable by the investigator during the entire period of administration of the study treatment and up to 6 months after the treatment end, for female and male patients.

⁃ Signature of the consent form before any study-specific procedure.

⁃ Covered by the French health insurance.