Efficacy and Safety of L-asparaginase Encapsulated in RBC Combined With Gemcitabine or FOLFOX in 2nd Line for Progressive Metastatic Pancreatic Carcinoma

Inclusion Criteria: A patient is eligible for the study if all of the following criteria are met: * Advanced or metastatic exocrine pancreatic adenocarcinoma, confirmed histologically * Available archival tumor tissue block with sufficient tissue either from primary tumor and/or from metastatic lesions for biomarker testing; alternatively, unstained slides with sufficient tissue may be substituted * Only 1 prior systemic therapy for advanced or metastatic disease. NOTE: Patient must be eligible to 2nd line gemcitabine or mFOLFOX6 treatment Documented disease progression during or following first-line therapy for advanced disease * Measurable lesion (\>1cm) as assessed by CT scan or MRI (Magnetic Resonance Imaging) according to RECIST criteria (version 1.1) * Age 18 years and older * ECOG performance status 0 or 1 * Ability to understand, and willingness to sign, a written informed consent and to comply with the scheduled visits, treatment plans, laboratory tests, and other study procedures. * Patient beneficiary of a Social Security Insurance if applicable Exclusion Criteria: A patient is excluded from the study if any of the following criteria are met: * Patient who have received Oxaliplatin in first line will not be eligible in FOLFOX arm; Patient who received Gemcitabine in first line will not be eligible in Gemcitabine arm * Resectable pancreatic adenocarcinoma * Known hypersensitivity to L-asparaginase or have had prior exposure to any form of L-asparaginase * Anti-vitamin K treatment. Replacement with low molecular weight heparin treatment if required * Inadequate organ functions: * hemoglobin \< 9.0 g/dl, neutrophil count \< 1.5 x 109/L, platelets \< 100 x 109/L. * Liver or pancreatic function abnormalities * AST or ALT \> 3 x ULN, or * Total bilirubin \> 1.5 x ULN, or * Lipase \> 2 x ULN with suggestive clinical sign of pancreatitis or \> 3N without suggestive clinical sign * Renal insufficiency: Renal clearance determined by the Cockroft and Gault Formula \< 60 mL/min * Current or prior coagulopathy disorders in the last month * PT ≥1.5 fold the upper limit of normal value or * INR ≥1.5 fold the upper limit of normal value or * Fibrinogen ≤ 0.75 fold the lower limit of normal value * Known Infection: HIV, active hepatitis related to B or C virus * Concurrent active malignancies (with the exception of in situ carcinoma of the cervix and inactive non melanoma skin cancer * Other serious conditions than pancreatic cancer according to investigator's opinion * NYHA Grade ≥ 2 congestive heart failure * Systemic chemotherapy or radiation within the last 3 weeks or major surgery within 4 weeks NOTE: chemotherapy or radiation therapy given in less than 3 weeks is allowed, provided patient recovered from all related toxicities * History of grade 3 blood transfusion reaction (life threatening situation) * Presence of anti-erythrocyte antibodies (auto-antibodies or anti-public antibodies) preventing from getting a compatible packed Red Blood Cells for the patient * Participation in another concurrent clinical trial * Women of child-bearing potential and men with partners of childbearing potential without effective contraception as well as pregnant or breast feeding women * Other severe acute/chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study.