A Phase II, Open-label Pilot Study Evaluating the Safety and Activity of Liposomal Irinotecan in Combination With 5-FU and Oxaliplatin in Preoperative Treatment of Pancreatic Adenocarcinoma (NEO-Nal- IRI Study)

• Must be at least 18 years of age.

• A new clinical diagnosis of resectable or borderline resectable, previously untreated pancreatic adenocarcinoma confirmed by pathologic specimen evaluation

• No clinical evidence of metastatic disease

• Potentially resectable local disease, as confirmed by CT or MRI of the abdomen

• ECOG performance status of 0 or 1

• Any biliary obstruction must have been treated.

• Subjects with known or suspected Gilbert's disease must be formally tested for UGT1A1\*28 with results available to study team prior to treatment initiation

• Adequate organ function; as defined by:

• i. Hematologic-

⁃ ANC \> 1,500 cells/μl without the use of hematopoietic growth factors; and

⁃ Platelet count \> 100,000 cells/μl; and

⁃ Hemoglobin \> 9 g/dL (blood transfusions are permitted for patients with hemoglobin levels below 9 g/dL)

‣ ii. Hepatic-

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‣ Serum total bilirubin within 1.5 x upper limit of normal (ULN) for the institution, with a trend downwards (biliary drainage is allowed for biliary obstruction),

⁃ AST and ALT less than or equal to 2.5 x ULN

‣ iii. Renal- Serum creatinine less than or equal to 1.5 x ULN

‣ iv. Cardiac- Normal ECG or ECG without any clinically significant findings as defined by the treating physician

• Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 7 months after the last dose of study drug to minimize the risk of pregnancy

• Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 4 months following the last dose of study drug.