A Study of the Safety and Activity of Liposomal Irinotecan in Combination With the 5-FU and Oxaliplatin in the Preoperative Treatment of Pancreatic Adenocarcinoma

Inclusion Criteria:

- 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

- No clinical evidence of metastatic disease

- Potentially resectable 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-

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

2. Platelet count > 100,000 cells/μl; and

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

ii. Hepatic-

1. Serum total bilirubin within normal range for the institution (biliary drainage is
allowed for biliary obstruction),

2. AST and ALT less than or equal to 2.5 x ULN

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

iv. Cardiac-

a. 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 6 weeks 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 6 weeks following the
last dose of study drug.

Exclusion Criteria:

- A medical history of prior anti-cancer treatment for pancreatic cancer.

- Locally advanced unresectable disease or evidence of metastatic disease.

- Any other invasive malignancy within the past three years.

- Presence of any known contraindications to or hypersensitivities to the
investigational products.

- Use of strong CYP3A4 inhibitors or inducers which cannot be discontinued prior to
study entry.

- A non-surgical candidate.

- Subject is unable to understand, provide consent or comply with study requirements,
treatments or instructions in the opinion of the treating physician.

- Uncontrolled diarrhea, active infection, known interstitial lung disease or other
medical condition that precludes safe administration of this combination therapy
consistent with manufacturer recommendations.

- Unwilling/unable to comply with birth control requirements while on study.

- Females or males of childbearing potential who are unwilling or unable to use an
acceptable method to avoid pregnancy for the entire study period and for at least 6
weeks after the last dose of study drug.

- Females who are pregnant or breastfeeding.

- History of any other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of protocol therapy or that might affect the interpretation of
the results of the study or that puts the subject at high risk for treatment
complications, in the opinion of the treating physician.

- Prisoners or subjects who are involuntarily incarcerated.

- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical illness.

- Subjects demonstrating an inability to comply with the study and/or follow-up
procedures.

- Known dihydrypyrimidine (DPD) deficiency