Inclusion Criteria:

- Exocrine pancreatic adenocarcinoma cytologically or histologically confirmed

- Locally advanced and non-resectable with invasion of the superior mesenteric artery
(stage III) or metastatic (stage IV) as defined by TNM 2002 classification (UICC
2002)

- resistant to a first or second line chemotherapy with gemcitabine

- Patient aged between 18 to 70 years

- Signed Informed Consent Form

- Life expectancy ≥ 12 weeks

- Accurate measurement of tumor volume by imagery (in at least one dimension)

- Presence of one or several tumor markers (CEA and CA 19.9)

- ECOG Prognostic Score : 0, 1 or 2

- Patient beneficiary of a Social Security Insurance

Exclusion Criteria:

- Patient with an endocrine or acinar pancreatic tumor

- Patient with known or suspected cerebro-meningeal metastases

- Haemoglobin level greater than 13 g/L

- Patient hypersensitive to L-asparaginase or have had prior exposure to any form of
L-asparaginase

- Splenic vein thrombosis < 3 months or under active treatment

- Anti-vitamin K treatment

- Hepatic Insufficiency unrelated to pancreatic cancer

- Renal insufficiency unrelated to pancreatic cancer

- Pancreatitis or pancreatitis history unrelated to pancreatic cancer

- Insulin-dependant diabetes mellitus unrelated to pancreatic cancer

- Current or prior coagulopathy disorders unrelated to pancreatic cancer

- ECOG Prognostic Score 3 or 4

- History of grade 3 blood transfusion reaction (life threatening situation)

- Presence of rare and dangerous anti-erythrocyte antibodies preventing from getting a
compatible packed Red Blood Cells for the patient

- Patient already included in another clinical trial

- Pregnancy, breast-feeding or absence of secured contraception

- Unwillingness to sign the informed consent form