Trial to Investigate Intensified Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Cancer

Inclusion Criteria:

* Adult patients ≥ 18 years and ≤ 75 years of age
* Histologic or cytologic proven ductal adenocarcinoma of the pancreas (histologic confirmation of diagnosis is preferred)
* No distant metastases
* De novo, treatment-naïve unresectable or borderline resectable LAPC; evaluation of unresectable and borderline resectable status according to NCCN- Clinical Practice Guidelines in Oncology "pancreatic adenocarcinoma" version 1.2013. Applicable criterion/criteria have to be indicated.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Total bilirubin ≤ 2 mg/dL. Patients with a biliary stent may be included provided that bilirubin level after stent insertion decreased to ≤ 2 mg/dL and there is no cholangitis.
* Adequate renal, hepatic and bone marrow function, defined as
* Serum creatinine ≤ 1.25 x Upper limit of normal (ULN)
* Calculated creatinine clearance ≥ 60 mL/min according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
* Aspartate aminotransferase (AST)/(serum glutamic oxaloacetic transaminase)GOT and/or Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (GPT) ≤ 2.5 x ULN
* Partial thromboplastin time (PTT) ≤ 1.5 x ULN and Quick value ≥ 70%
* Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
* Haemoglobin ≥ 8g/dL
* Platelets ≥ 100 x 109/L
* Females of childbearing potential (FCBP) must have a negative pregnancy test within 7 days of the first application of study treatment and must agree to use effective contraceptive birth control measures (Pearl Index \< 1) during the course of the trial and for at least 1 month after last application of study treatment.

A female subject is considered to be of childbearing potential unless she is age ≥ 50 years and naturally amenorrhoeic for ≥ 2 year, or unless she is surgically sterile.

* Males must agree not to father a child during the course of the trial and for at least 6 months after last administration of study drugs.
* Signed and dated informed consent before the start of any specific protocol procedures
* Patient's legal capacity to consent to study participation

Exclusion Criteria:

* Evidence of distant metastases. In case of radiological suspicion of peritoneal carcinomatosis or ascites histological or cytological verification is required e.g. by means of exploratory laparoscopy
* Local relapse of the pancreatic adenocarcinoma prior treated with surgical resection
* Any previous treatment of the pancreatic carcinoma (radiotherapy, chemoradiotherapy, chemotherapy, targeted tumor therapy, local ablative therapy)
* Contraindication for pancreas resection (pancreatic head resection, distal pancreatectomy with splenectomy, or complete pancreatectomy)
* Larger surgical interventions within 4 weeks before study enrolment and/or diagnostic laparotomy with or without gastroenterostomy and with or without biliodigestive anastomosis within 2 weeks before first application of study treatment. Wound healing must be also completed before first application of study treatment.
* Known chronic diarrhoea
* Peripheral polyneuropathy \> grade 1
* Known dihydropyrimidine dehydrogenase (DPD) deficiency
* Medical history of interstitial lung disease (ILD) or pulmonary fibrosis
* Hypersensitivity against any of the study drugs (nab-paclitaxel, gemcitabine, oxaliplatin, irinotecan, 5-fluorouracil, folinic acid), or the ingredients of these drugs
* Active or uncontrolled bacterial, viral, or fungal infection that requires systemic treatment
* Known HIV- infection or active Hepatitis B virus (HBV)- or Hepatitis C virus (HCV) infection
* Convulsion disorder that requires anticonvulsive treatment
* Clinically significant cardiovascular or vascular disease or disorder ≤ 6 months before study enrolment (e.g. myocardial infarction, unstable angina pectoris, chronic heart failure New York Heart Association (NYHA) ≥ grade 2, uncontrolled arrhythmia, cerebral infarction)
* Any other severe concomitant disease or disorder, which could influence patient's ability to participate in the study and his/her safety during the study or interfere with interpretation of study results e.g. severe hepatic, renal, pulmonary, metabolic, or psychiatric disorders
* Requirement for concomitant antiviral treatment with sorivudine or brivudine
* Requirement of immunosuppressive treatment
* Continuing anticoagulant therapy with coumarin derivatives (treatment with low-molecular weight heparin allowed)
* Continuing abuse of alcohol, drugs, or medical drugs
* Pregnant or breast feeding females
* Participation in any other clinical trial or treatment with any experimental drug within 28 days before enrolment to the study or during study participation until the end of treatment visit.
* Previous or concurrent malignant tumor disease other than underlying tumor disease with the exception of cervical cancer in situ, adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, superficial bladder tumors (Ta,Tis, and T1) or any curatively treated tumors \> 5 years prior to enrolment