A Phase II Study of Neoadjuvant FOLFIRINOX

Inclusion Criteria:

1. ≥ 18 years old at the time of informed consent

2. Able to provide written informed consent and HIPAA authorization

3. ECOG performance status of 0 or 1

4. Patient must be eligible for abdominal surgery

5. Histologically confirmed adenocarcinoma of the pancreas that has been documented to be
resectable by standardized radiographic criteria by a pancreatic surgeon

6. Patients must to have tumor tissue collected prior to enrolling on this trial. Up to
10 patients will be accepted with no pre-treatment research tissue collection or
tissue collection from an outside institution.

a.If the tissue is from an outside institution, it must be reviewed at Indiana
University Health Pathology Department if a biopsy was performed outside of this
institution.

7. Women of childbearing potential definition (WOCBP) must have a negative serum or urine
pregnancy test performed within 14 days prior to initiation of FOLFIRINOX.

Any woman (regardless of sexual orientation, having undergone a tubal ligation, or
remaining celibate by choice) is classified as WOCBP if she meets the following
criteria:

1. Has not undergone a hysterectomy or bilateral oophorectomy; or

2. Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months).

8. WOCBP and men must agree to use adequate contraception prior, to study entry, for the
duration of study participation, and 8 weeks after the end of treatment.

9. Patients must have adequate organ function as defined by the following laboratory
values at study entry:

1. Hemoglobin ≥ 9 g/dL (transfusions are acceptable)

2. ANC ≥ 1.5 x 109/L

3. Platelets ≥ 100 x 109/L

4. Creatinine ≤ 1.5 x ULN, or creatinine clearance ≥ 50 mL/min (estimated by
Cockcroft-Gault or measured)

5. Total bilirubin ≤ 1.5 x ULN

6. AST/ALT ≤ 3 x ULN

Exclusion Criteria:

1. Prior therapy for pancreatic adenocarcinoma

2. Other malignancies within the past 3 years except for the following: adequately
treated cervical or vulvar carcinoma in situ, treated basal cell or squamous carcinoma
of the skin, superficial bladder tumors (Ta, Tis & T1), ductal carcinoma in situ
(DCIS) of the breast and low grade prostate cancer. Any cancer curatively treated >3
years prior to entry with no clinical evidence of recurrence is permitted.

3. Hypersensitivity to 5FU, oxaliplatin (or other platinum agents), irinotecan (or to
their excipients).

4. Participation in any investigational drug study within 4 weeks preceding the start of
study treatment. Patients are not permitted to participate in another investigational
drug study while being treated on this protocol.

5. Inability to receive a port or PICC line.

6. History of or suspected Gilbert's Disease (testing not required if presence is not
suspected).

7. Baseline peripheral neuropathy/paresthesia grade ≥ 1.

8. Active hepatitis B, unless patient has been on antiviral agents for at least 2 months
(baseline testing not required).

9. Active clinically serious infections (> grade 2).

10. Major surgery or significant traumatic injury within 8 weeks of first study drug. A
core pancreatic or liver biopsy does not preclude the patient from the study.

11. Unable or unwilling to discontinue use of ketoconazole or St John's wort. Use of
phenytoin, carbamazepine, phenobarbital, rifampin and rifabutin is discouraged, but
not contraindicated. If patients require phenytoin, carbamazepine or phenobarbital
monitoring of drug levels is suggested during the study.

12. Pregnant or lactating women.

13. Psychological, familial, sociological or geographical condition potentially hampering
compliance with the study protocol and follow-up schedule; those conditions should be
discussed with the patient before registration in the trial.