24BRO681 : Alternating Gnp and mFOLFIRINOX for BR-PDAC

The purpose of this research is to study the effects and safety of alternating neoadjuvant chemotherapy on borderline resectable pancreatic cancer.

Inclusion Criteria: * Age ≥ 18 years * Diagnosis of BR-PDAC. The resectability should be officially determined with surgical oncologists at the Dartmouth Cancer Center (DCC) GI multidisciplinary Tumor Board based on NCCN Guidelines Version 2.2024 Pancreatic Adenocarcinoma. * Patients must be able and willing to provide informed consent. * Contrast-enhanced CT scan of the chest, abdomen, and pelvis performed within 45 days before registration. * ECOG Performance Status: 0-1. * Females of childbearing potential must have a negative pregnancy test done ≤ 14 days prior to study enrollment, and must agree to use a highly effective method of contraception throughout the course of protocol therapy. Exclusion Criteria: * Any prior receipt of chemotherapy or radiation therapy for PDAC. * Known DPYD poor metabolizer genotype. * Known BRCA1/2 or PALB2 mutations. If they are found to have BRCA1/2 or PALB2 mutation after inclusion to the trial, the participant will be taken off of protocol therapy (since platinum-containing therapy is preferred for these patients). * Any confirmed second malignancy that is likely to require systemic therapy during the study period, in the opinion of the enrolling investigator. * Any of the following baseline laboratory abnormalities: * Absolute neutrophil count (ANC) \< 2,500/mm3 * Platelet count \< 100,000/mm3 * Hemoglobin \< 7 g/dL * Creatinine \> 1.5 x upper limit of normal (ULN) * Total bilirubin \> 1.5 x ULN * AST/ALT \> 5 x ULN * Any peripheral sensory neuropathy that meaningfully impairs performance of instrumental activities of daily living, as evaluated by the enrolling investigator. * Patients who are unable to provide informed consent. * Patients who are pregnant or breastfeeding. * Patients who are incarcerated.