24BRO681 : Alternating Gnp and mFOLFIRINOX for BR-PDAC

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.