Inclusion Criteria:
* Must be at least 18 years of age.
* A new clinical diagnosis of resectable or borderline resectable, previously untreated pancreatic adenocarcinoma confirmed by pathologic specimen evaluation
* No clinical evidence of metastatic disease
* Potentially resectable local disease, as confirmed by CT or MRI of the abdomen
* ECOG performance status of 0 or 1
* Any biliary obstruction must have been treated.
* Subjects with known or suspected Gilbert's disease must be formally tested for UGT1A1\*28 with results available to study team prior to treatment initiation
* Adequate organ function; as defined by:
i. Hematologic-
1. ANC \> 1,500 cells/μl without the use of hematopoietic growth factors; and
2. Platelet count \> 100,000 cells/μl; and
3. Hemoglobin \> 9 g/dL (blood transfusions are permitted for patients with hemoglobin levels below 9 g/dL)
ii. Hepatic-
1. Serum total bilirubin within 1.5 x upper limit of normal (ULN) for the institution, with a trend downwards (biliary drainage is allowed for biliary obstruction),
2. AST and ALT less than or equal to 2.5 x ULN
iii. Renal- Serum creatinine less than or equal to 1.5 x ULN
iv. Cardiac- Normal ECG or ECG without any clinically significant findings as defined by the treating physician
* Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 7 months after the last dose of study drug to minimize the risk of pregnancy
* Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 4 months following the last dose of study drug.
Exclusion Criteria:
* A medical history of prior anti-cancer treatment for pancreatic cancer.
* Locally advanced unresectable disease or evidence of metastatic disease.
* Any other invasive malignancy within the past three years.
* Presence of any known contraindications to or hypersensitivities to the investigational products.
* Use of strong CYP3A4 inhibitors or inducers which cannot be discontinued prior to study entry.
* A non-surgical candidate.
* Subject is unable to understand, provide consent or comply with study requirements, treatments or instructions in the opinion of the treating physician.
* Uncontrolled diarrhea, active infection, known interstitial lung disease or other medical condition that precludes safe administration of this combination therapy consistent with manufacturer recommendations.
* Unwilling/unable to comply with birth control requirements while on study.
* Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 7 months for females and 4 months for males after the last dose of study drug.
* Females who are pregnant or breastfeeding.
* History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician.
* Prisoners or subjects who are involuntarily incarcerated.
* Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.
* Subjects demonstrating an inability to comply with the study and/or follow-up procedures.
* Known dihydrypyrimidine (DPD) deficiency
