Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with conventional treatments having little impact on disease course. Novel approaches are urgently needed to address inherent resistance to the current therapies and to identify new drugs or combinations that will have a high chance of success in pancreatic cancer patients. This proof-of-concept trial is studying the "dynamic" tumor response after the administration of a short course of gemcitabine and nab-paclitaxel (Abraxane) (a) during a window interval (4 weeks= 1 cycle) before surgery in resectable pancreatic cancer (cohort 1 = 21 patients) and (b) during at least 8 weeks (2 cycles) in locally advanced or metastatic pancreatic cancer (cohort 2 = 10 patients).

Pancreatic cancer is a hypoperfused tumor, characterized by a high stroma density precluding cytotoxics delivery to the epithelial tumoral compartment. There is thus a rationale for combining chemotherapy and antistromal drugs like nab-paclitaxel (Abraxane), a solvent (Cremophor® EL)-free, albumin-bound form of paclitaxel that has been initially developed to reduce the toxicities associated with Taxol injection while maintaining or improving its chemotherapeutic effect. This unique protein formulation provides a novel approach of increasing intra-tumoral concentrations of the drug by a receptor-mediated transport process allowing transcytosis across the endothelial cell.

Abraxane has been approved for commercialization in 38 countries, including the US, Canada, the EU, Australia, China, India and Korea for the treatment of women with metastatic breast cancer. Abraxane alone and in combination is being evaluated in a number of cancers, including metastatic melanoma, non-small cell lung cancer, pancreatic cancer and other solid tumors.

Inclusion Criteria:

• Histo(cyto)logically proven ductal pancreatic adenocarcinoma;
• Resectable or potentially resectable tumor; resectability assessed during a multidisciplinary meeting with expert surgeon and radiologist (cohort 1), or locally advanced and/or metastatic tumor (cohort 2);
• First line chemotherapy;
• Age > 18 years;
• WHO performance status (PS) grade 0 or 1;
• Absolute neutrophil count > 1.5 x 10 9 / L, platelets > 100 x 10 9/ L, creatinine clearance (Cockcroft and Gault formula) > 60 ml/min, haemoglobin level > 10 g/dl (transfusions authorized), bilirubin<1.5 g/dl;
• Optimal biliary drainage;
• Women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or tubal ligation of who has not been naturally postmenopausal for at least 24 consecutive months, must have a negative serum or urine pregnancy test prior to treatment. All WCBP, all sexually active male patients, and all partners of patients must agree to use adequate methods of birth control throughout the study;
• Signed informed consent.

Exclusion Criteria:

• Previous anticancer therapy for the pancreatic adenocarcinoma;
• Biliary obstruction without endoscopic biliary drainage;
• Any contre-indication for surgery;
• Prior malignancy (except non-melanoma skin cancer, and in situ carcinoma of the uterine cervix treated with a curative intent and any other tumor in complete remission with a disease-free interval > 3 years);
• Uncontrolled congestive heart failure or angina pectoris, myocardial infarction within 1 year prior to study entry, uncontrolled hypertension (systolic pressure > 160 mm or diastolic pressure > 100 mm under well conducted antihypertensive treatment), QT prolongation;
• Major uncontrolled infection;
• Severe hepatic impairment;
• Any medical, psychological, or social condition, which, in the opinion of the investigator, could hamper patient's compliance to the study protocol and/or assessment/interpretation of the data;
• Pregnant or lactating women, or patients of both genders with procreative potential not using adequate contraceptive methods;
• Patients receiving or having received any investigational treatment within 4 weeks prior to study entry, or participating to another clinical study; patients previously enrolled into this study.