NALIRIFOX Before Surgery for the Treatment of Borderline Resectable Pancreatic Ductal Adenocarcinoma, Nectar Trial

Inclusion Criteria: * Age ≥ 18 years of age * Have histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC) that is borderline resectable (BR) using the National Comprehensive Cancer Network criteria * Have a documented Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 * Absolute neutrophil count (ANC) ≥ 1,500 cells/uL without the use of hematopoietic growth factors * Platelet count ≥ 100,000 cells/uL * Hemoglobin ≥ 9 g/dL * Plasma total bilirubin ≤ upper limit of normal (ULN) (biliary drainage is allowed for biliary obstruction) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN * Creatine clearance of \> 30 mL/min (per Cockroft-Gault equation) * Plasma albumin ≥ 3 g/dL * Have measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria * Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately * Participant must understand the investigational nature of this study and sign an independent ethics committee/institutional review board approved written informed consent form (ICF) prior to receiving any study related procedure Exclusion Criteria: * Patients who have had previous chemotherapy or radiotherapy for PDAC * Patients with resectable, unresectable, or metastatic PDAC * Presence of germline glucuronosyltransferase (UGT) 1A1 (\*28 or \*6) or dihydropyrimidine dehydrogenase (DPD) polymorphisms (DPYD\*2A \[rs3918290, c.1905+1G\>A, IVS14+1G\>A\], c.2846A\>T \[rs67376798, D949V\], c.1679T\>G \[rs55886062, DPYD\*13, I560S\], and c.1236G\>A \[rs56038477, E412E, in haplotype B3\]) known to significantly impact CPT-11 and fluorouracil metabolism and associated with increased risk for toxicities * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant or nursing female participants * Unwilling or unable to follow protocol requirements * Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug