Preoperative Extended Chemotherapy vs. Chemotherapy Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Head of the Pancreas

• Confirmation of radiographic stage as borderline resectable disease by real-time Alliance central radiographic review

• No prior chemotherapy or radiation for pancreatic cancer

• No definitive resection of pancreatic cancer

• Chronic concomitant treatment with strong inhibitors of cytochrome p450, family 3, subfamily a, polypeptide 4 gene (CYP3A4) is not allowed on this study; patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study

• Chronic concomitant treatment with strong CYP3A4 inducers is not allowed; patients must discontinue the drug 14 days prior to the start of study treatment

• No grade \>= 2 neuropathy

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

• No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease) within 28 days of registration

• Not pregnant and not nursing; for women of childbearing potential only, a negative pregnancy test done =\< 7 days prior to registration is required

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

• Absolute neutrophil count (ANC) \>= 1,500/mm\^3

• Platelet count \>= 100,000/mm\^3

• Creatinine =\< 1.5 x upper limit of normal (ULN) or

• Calculated (calc.) creatinine clearance \> 45 mL/min

• Total bilirubin =\< 2.0 mg/dL

• Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =\< 2.5 X upper limit of normal (ULN)