Phase II Single Arm Clinical Trial of FOLFIRINOX for Unresectable Locally Advanced and Borderline Resectable Pancreatic Cancer

Inclusion Criteria:

- Biopsy confirmed adenocarcinoma of the pancreas.

- Measurable or non-measurable but evaluable (as determined by Response Evaluation
Criteria in Solid Tumors version 1.1 [RECIST 1.1]) unresectable locally advanced
(ULA) or borderline resectable (BR) disease that is not amenable to curative intent
therapy. Baseline CT abdomen and chest (or MRI abdomen) within 28 days prior to
initiation of FOLFIRINOX is required.

- ECOG performance status 0 or 1.

- No prior chemotherapy or chemoradiotherapy for pancreatic cancer.

- Age ≥ 18 years of age.

- Laboratory requirements at study entry:

- Hemoglobin ≥ 10 g/dL (transfusions are acceptable)

- ANC ≥ 1.5 x 109/L

- Platelets ≥ 100 x 109/L

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

- Total bilirubin ≤ 1.5 x ULN

- AST/ALT ≤ 3 x ULN

- GGT ≤ 5 x ULN

- Life expectancy of at least 6 months.

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

- 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.

- Before patient registration, written informed consent must be given.

Exclusion Criteria:

- Local recurrence or resectable recurrence of pancreatic cancer.

- Other malignancies within the past 3 years except for adequately treated cervical or
vulvar carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors
(Ta, Tis & T1). Any cancer curatively treated >3 years prior to entry is permitted.

- Hypersensitivity to 5FU, oxaliplatin or other platinum agent, or irinotecan or to
their excipients. Known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency.

- 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.

- Cardiac disease: Congestive heart failure symptoms > class II NYHA. Unstable angina
(anginal symptoms at rest) or new onset angina beginning within the last 3 months.
Myocardial infarction within the past 6 months. Cardiac ventricular arrhythmias
requiring anti-arrhythmic therapy.

- History of or suspected Gilbert's Disease (baseline testing not required).

- Baseline peripheral neuropathy/paresthesia grade ≥ 1.

- Active hepatitis B, unless patient has been on stable meds for at least 2 months
(baseline testing not required).

- Active clinically serious infections (> grade 2).

- Any other hemorrhage/bleeding event > CTCAE Grade 3 within the 12 weeks prior to the
first dose FOLFIRINOX.

- Evidence or history of bleeding diathesis or coagulopathy. NOTE: If therapeutic
anticoagulation required, the investigator is encouraged to switch patient to (or
maintain on) low molecular weight heparin during the trial.

- Major surgery, open biopsy 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.

- Unable or unwilling to discontinue use of ketoconazole or St John's wort. Use of
CYP3A4 enzyme-inducing drugs and strong CYP3A4 inhibitors is discouraged, but not
contraindicated.

- Active drug or alcohol abuse.

- Pregnant or lactating women.

- 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.