Preoperative Folfirinox for Resectable Pancreatic Adenocarcinoma - A Phase II Study

PRIMARY OBJECTIVES:

I. To determine feasibility of preoperative FOLFIRINOX for resectable pancreatic
adenocarcinoma.

SECONDARY OBJECTIVES:

I. To determine safety and toxicity of preoperative FOLFIRINOX. II. To determine response
rate. III. To determine proportion achieving major pathologic response - per College of
American Pathologists (CAP) criteria.

IV. To determine proportion achieving R0 resection. V. To determine perioperative (30-day)
mortality. VI. To determine the role of cancer antigen (CA)19.9 as potential prognostic
and/or predictive biomarker.

VII. To determine progression-free survival. VIII. To determine overall survival.

OUTLINE:

Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride intravenously (IV)
over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and
fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment
repeats every 14 days for 6 courses in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed up every 3 months.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed carcinoma of the
pancreas; most cases will be adenocarcinoma; cases with "undifferentiated" or "poorly
differentiated" carcinoma will also be eligible

- There should be no evidence of metastatic disease on imaging of the chest, abdomen,
and pelvis; this imaging should be either a contrast-enhanced computed tomography (CT)
scan, or a contrast-enhanced magnetic resonance imaging (MRI) scan; positron emission
tomography (PET) scans alone will not be adequate alternatives; there should be no
evidence of occult metastatic disease in the abdomen, confirmed by laparoscopic
examination

- The primary tumor must be resectable, defined as no involvement (abutment or
encasement) of the major arteries (celiac, common hepatic, superior mesenteric) and
interface between tumor and vessel (portal, superior mesenteric veins) wall to be less
than 180 degrees of the circumference of the vessel wall; this should be confirmed by
imaging of the abdomen, either by a contrast-enhanced computed tomography (CT) scan,
or a contrast-enhanced magnetic resonance imaging (MRI) scan; PET scans will not be
adequate alternatives; for each patient, the resectability must be reviewed by one of
the study surgeons

- Patient must not have received any cancer-directed therapy (e.g., surgery,
chemotherapy, radiation therapy, biologic therapy) for the index diagnosis

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Hemoglobin >= 10.0 g/dl

- Absolute neutrophil count >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- Total bilirubin =< 1.5 X institutional upper limit of normal

- Serum creatinine within normal institutional limits, or creatinine clearance
(calculated by Cockcroft-Gault) >= 60 mL/min/1.73 m^2 for patients with creatinine
levels above institutional normal

- Women of child-bearing potential and men must agree to use adequate contraception
(double-barrier method of birth control or abstinence) for the duration of study
participation and for 6 months after completing chemotherapy; should a woman become
pregnant or suspect that she is pregnant while she or her partner is participating in
this study, she should inform the treating physician immediately

- Subjects must have the ability to understand and the willingness to sign a written
informed consent document

Exclusion Criteria:

- Patients with uncontrolled intercurrent illness including, but not limited to ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements

- Pregnant or breastfeeding women

- Pre-existing peripheral neuropathy (grade I or higher)