Combination Chemotherapy, Gemcitabine Hydrochloride, and Radiation Therapy Before Surgery in Treating Patients With Borderline Resectable Pancreatic Cancer

PRIMARY OBJECTIVES:

I. To assess the efficacy, measured as the proportion of R0 resections, of
fluorouracil-leucovorin calcium-irinotecan hydrochloride-oxaliplatin (FOLFIRINOX)
chemotherapy regimen followed by gemcitabine based chemoradiotherapy when used as
preoperative therapy in patients with borderline resectable adenocarcinoma of the pancreas.

SECONDARY OBJECTIVES:

I. To measure the overall response rate (ORR). II. To evaluate overall survival (OS). III.
To evaluate progression free survival (PFS). IV. To evaluate safety and toxicity associated
with chemotherapy and radiotherapy.

V. To assess adverse events related to surgery. VI. To assess the proportion of patients
able to undergo resection. VII. To assess proportion of patients requiring vascular
reconstruction.

OUTLINE:

CHEMOTHERAPY REGIMEN: Patients receive oxaliplatin intravenously (IV) over 2 hours,
leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 90 minutes on day
1, and fluorouracil IV over 46 hours on days 1-3. Treatment repeats every 14 days for 4
courses in the absence of disease progression or unacceptable toxicity. Patients not
achieving disease progression proceed to chemoradiotherapy.

CHEMORADIOTHERAPY REGIMEN: Beginning 4-6 weeks after completion of chemotherapy, patients
undergo intensity-modulated radiation therapy (IMRT) on 5 consecutive days per week for a
total of 28 fractions and receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8,
15, 22, 29, and 36. Treatment continues in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 30 months.

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the pancreas

- Only patients that have not received any prior treatment for pancreas cancer are
eligible for this treatment protocol

- Patients are not required to have measurable disease by traditional Response
Evaluation Criteria in Solid Tumors (RECIST) criteria, as lesions in the pancreas are
notoriously hard to measure radiographically; however, patients must have disease
which is evaluable for resection

- Disease should be determined as "borderline resectable" according to the Expert
Consensus Statement published by Callery et al:

- No distant metastasis

- Venous involvement of the superior mesenteric vein (SMV)/portal vein
demonstrating tumor abutment with or without impingement and narrowing of the
lumen, encasement of the SMV/portal vein but without encasement of the nearby
arteries, or short segment venous occlusion resulting from either tumor thrombus
or encasement but with suitable vessel proximal and distal to the area of vessel
involvement, allowing for safe resection and reconstruction

- Gastroduodenal artery encasement up to the hepatic artery with either short
segment encasement or direct abutment of the hepatic artery, without extension
to the celiac axis

- Tumor abutment of the superior mesenteric artery (SMA) not to exceed greater
than 180 degrees of the circumference of the vessel wall

- Life expectancy of greater than 6 months

- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 80%)

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin =< 2 mg/dl

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 X institutional upper limit of normal

- Creatinine within normal institutional limits OR creatinine clearance >= 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

- Ability to understand and the willingness to sign a written informed consent document

- Patients may not be receiving any other concurrent chemotherapy, immunotherapy, or
radiotherapy

Exclusion Criteria:

- Patients who have had prior chemotherapy or radiotherapy for the treatment of
pancreas cancer

- Patients may not be receiving any other investigational agents

- Evidence of extent of pancreatic cancer beyond that defined as "borderline
resectable" above (locally advanced or distant disease); peripancreatic lymph node
involvement, either confirmed or suspected, will not be considered distant disease
unless the lymph node involvement extends outside of the field of resection

- Patients with known brain metastases should be excluded from this clinical trial

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to 5-fluorouracil, oxaliplatin, irinotecan or gemcitabine

- Any concurrent active malignancy other than non-melanoma skin cancers or
carcinoma-in-situ of the cervix; patients with previous malignancies but without
evidence of disease for > 3 years will be allowed to enter the trial; patients with a
history of a T1a or b prostate cancer (detected incidentally at transurethral
resection of the prostate [TURP] and comprising less than 5% of resected tissue) may
participate if the prostate-specific antigen (PSA) remained within normal limits
since TURP removal

- 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 women are excluded from this study; breastfeeding should be discontinued if
the mother is treated

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible