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.