∙ PRE-REGISTRATION:

• Pathology: Histologic or cytologic proof of pancreatic adenocarcinoma or adenosquamous carcinoma

• TNM Stage: Tx-4, N0-1, M0 (M0 disease does not include spread to distant lymph nodes and organs)

• Resectable Primary Tumor: Local radiographic reading must be consistent with resectable disease defined as the following on 1) arterial and venous phase contrast-enhanced abdominal/pelvic CT scan or abdominal/pelvic magnetic resonance imaging (MRI) scan and 2) chest CT:

‣ No involvement or abutment of the celiac artery, common hepatic artery, superior mesenteric artery, or replaced right hepatic artery (if applicable)

⁃ Less than 180 degree interface between tumor and vessel wall of the portal vein or superior mesenteric vein, and patent portal vein/splenic vein confluence

⁃ No evidence of metastatic disease

• Measurable disease or non-measurable disease o Non-measurable disease is defined as cytologic or histologic confirmation of adenocarcinoma of adenosquamous carcinoma by fine needle aspiration or core-biopsy of the pancreas without measurable disease by radiographic imaging

∙ REGISTRATION:

• Confirmation of resectable disease by real-time central imaging review by the Alliance Imaging Core Lab at Imaging and Radiation Oncology Core (IROC) Ohio

• Determined to be appropriate candidate for curative-intent pancreatectomy by surgeon intending to perform the resection

• No prior radiation therapy, chemotherapy, targeted therapy, investigational therapy, or surgery for pancreatic cancer

• Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects.

• Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 14 days prior to registration is required

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Total Neuropathy Score \< 2

• Absolute neutrophil count (ANC) \>= 1,500/uL

• Platelet count \>= 100,000/uL

• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (If obstructive jaundice is present, then biliary drainage must be initiated and total bilirubin =\< 3.0)

• Creatinine =\< 1.5 x ULN OR calculated (Calc.) creatinine clearance \>= 30 mL/min (Calculated using the Cockcroft-Gault equation)

• No known Gilbert's Syndrome or known homozygosity for UGAT1A1\*28 polymorphism

• No comorbid conditions that would prohibit curative-intent pancreatectomy

• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug prior to registration

• Chronic concomitant treatment with strong inducers of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inducers must discontinue the drug prior to registration