FOLFIRINOX for Unresectable Locally Advanced and Borderline Resectable Pancreatic Cancer

Inclusion Criteria: * Biopsy confirmed adenocarcinoma of the pancreas. * Measurable or non-measurable but evaluable (as determined by Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\]) unresectable locally advanced (ULA) or borderline resectable (BR) disease that is not amenable to curative intent therapy. Baseline CT abdomen and chest (or MRI abdomen) within 28 days prior to initiation of FOLFIRINOX is required. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. * No prior chemotherapy or chemoradiotherapy for pancreatic cancer. * Age ≥ 18 years of age. * Laboratory requirements at study entry: * Hemoglobin ≥ 10 g/dL (transfusions are acceptable) * absolute neutrophil count (ANC) ≥ 1.5 x 109/L * Platelets ≥ 100 x 109/L * Creatinine ≤ 1.5 x upper limit of normal (ULN), or creatinine clearance ≥ 50 mL/min (estimated by Cockcroft-Gault or measured) * Total bilirubin ≤ 1.5 x ULN * aspartate aminotransferase/Alanine Aminotransferase (AST/ALT) ≤ 3 x ULN * Gamma-Glutamyl Transferase (GGT) ≤ 5 x ULN * Life expectancy of at least 6 months. * Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test performed within 14 days prior to initiation of FOLFIRINOX. * WOCBP and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and 8 weeks after the end of treatment. * Before patient registration, written informed consent must be given. Exclusion Criteria: * Local recurrence or resectable recurrence of pancreatic cancer. * Other malignancies within the past 3 years except for adequately treated cervical or vulvar carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis \& T1). Any cancer curatively treated \>3 years prior to entry is permitted. * Hypersensitivity to 5FU, oxaliplatin or other platinum agent, or irinotecan or to their excipients. Known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. * Participation in any investigational drug study within 4 weeks preceding the start of study treatment. Patients are not permitted to participate in another investigational drug study while being treated on this protocol. * Cardiac disease: Congestive heart failure symptoms \> class II New York Heart Association (NYHA). Unstable angina (anginal symptoms at rest) or new onset angina beginning within the last 3 months. Myocardial infarction within the past 6 months. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. * History of or suspected Gilbert's Disease (baseline testing not required). * Baseline peripheral neuropathy/paresthesia grade ≥ 1. * Active hepatitis B, unless patient has been on stable meds for at least 2 months (baseline testing not required). * Active clinically serious infections (\> grade 2). * Any other hemorrhage/bleeding event \> CTCAE Grade 3 within the 12 weeks prior to the first dose FOLFIRINOX. * Evidence or history of bleeding diathesis or coagulopathy. Note: If therapeutic anticoagulation required, the investigator is encouraged to switch patient to (or maintain on) low molecular weight heparin during the trial. * Major surgery, open biopsy or significant traumatic injury within 8 weeks of first study drug. A core pancreatic or liver biopsy does not preclude the patient from the study. * Unable or unwilling to discontinue use of ketoconazole or St John's wort. Use of CYP3A4 enzyme-inducing drugs and strong CYP3A4 inhibitors is discouraged, but not contraindicated. * Active drug or alcohol abuse. * Pregnant or lactating women. * Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.