OXIRI [Oxaliplatin (O), Xeloda (X) and Irinotecan (I)] in Pancreatic Adenocarcinoma

Inclusion Criteria: 1. Patients between 21 to 75 years of age 2. A histopathologically or cytological confirmed diagnosis of locally advanced and/or metastatic PDAC that is unresectable 3. Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) ver 1.1 criteria 4. Life expectancy of at least 12 weeks 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 6. Adequate hematologic function (neutrophils count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L) 7. Adequate hepatic function (total bilirubin ≤ 1.5 x the upper limits of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN 8. Adequate renal function (calculated creatinine clearance \> 50 mL/min) 9. Able to give informed consent 10. Toxicity related to previous radiotherapy or chemotherapy resolved to ≤ Grade 1 Exclusion Criteria: 1. History of prior malignancy except non-melanoma skin cancer within the last 5yrs 2. Uncontrolled central nervous system (CNS) metastases or carcinomatous meningitis 3. Uncontrolled concomitant medical illnesses (e.g. hypertension, myocardial infarct, heart failure, ventricular arrhythmia, diabetes, severe infection) 4. Major surgery within four weeks prior to study treatment 5. Patients on chronic immunosuppressive therapy 6. Pregnant or breast-feeding female patients 7. On anticoagulant therapy with vitamin K antagonists. 8. Dose-escalation cohort: * Patients homozygous for uridine diphosphate glucuronosyltransferase (UGT)1A1\*6/\*6 or UGT1A1\*28/\*28 * Previous oxaliplatin or irinotecan chemotherapy * Treatment with any of the following anti-cancer therapies prior to the first dose of OXIRI within the stated timeframes * Cyclical chemotherapy within a period of time that is shorter than the cycle length used for that treatment. Exception for weekly chemotherapy regimens, where a minimum of 2 week washout from the last dose is required. * Biological therapy (e.g., antibodies) within a period of time that is ≤ 5 t1/2 or ≤ 4 weeks, whichever is shorter, prior to starting study drug * Continuous or intermittent small molecule therapeutics within a period of time that is ≤ 5 t1/2 or ≤ 4 weeks (whichever is shorter) prior to starting study drug * Any other investigational agents within a period of time that is ≤ 5 t1/2 or less than the cycle length used for that treatment or ≤ 4 weeks (whichever is shortest) prior to starting study drug * Wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug 9. Dose-expansion cohort: * Previous chemotherapy or radiotherapy