Folfirinox or Gemcitabine-Nab Paclitaxel Followed by Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer

This pilot study will evaluate safety and tolerability of neoadjuvant chemotherapy followed
by SBRT. Patients with locally advanced pancreatic cancer (LAPC) and borderline pancreatic
inoperable cancer will be assigned to one of two treatment arms based upon performance status
and physician's discretion. The two treatment arms are: Folfirinox or gemcitabine-nab
paclitaxel (abraxane). There are no study drugs as all treatments are based on standard
clinical pathways.

After two cycles of treatment patients will be restaged with CT scans or imaging. If the
tumor remains resectable, borderline, or unresectable without progression of disease, then
the patient will proceed to SBRT.

Follow-up visits will continue every three months for up to one year or until progression of
disease.

Inclusion Criteria:

- Histologically or cytologically proven adenocarcinoma of the pancreas. Patients with
mixed tumor with predominant adenocarcinoma pathology can be enrolled.

- Subjects will be staged according to the 2010 American Joint Committee on Cancer
(AJCC) staging system with pathologic stage T1-4, being eligible; and have a primary
tumor of the pancreas (either pancreatic head, neck, uncinate process, or body/tail)

- The tumor must be deemed as being borderline/unresectable. Final CT confirmation of
surgical staging/ eligibility will be at the discretion of the pancreatic surgeon of
the patient.

- Disease must be confined to loco-regional site as confirmed by CT imaging and/or
diagnostic staging laparoscopy to avoid occult peritoneal deposits. Diagnostic
laparoscopy will be performed only if absolutely required

- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) on
imaging studies CT

- Karnofsky performance status greater than or equal to 70 or Eastern Cooperative
Oncology Group (ECOG) performance of 0-2.

- Age >18

- Estimated life expectance >12 weeks

- If female patient is of child bearing potential, she must have a negative serum
pregnancy test (βhCG) documented up to 72 hrs prior to administration of first study
drug

- Patient has screening blood work performed which includes the following (should be
drawn ≤14 days prior to enrollment)

- Absolute neutrophil count (ANC) >1.5 x 109/L

- Platelet count ≥100,000/mm3

- Hemoglobin (Hgb) ≥ 9g/dL

- Aspartate aminotransferase (AST), Alanine Aminotransferase (ALT) ≤ 2.5 x upper limit
of normal (ULN) Total Bilirubin ≤1.5 ULN

- Serum Cr within normal limits (WNL)

- Prothrombin Time and International Normalized Ratio (PT/INR) and Partial
Thromboplastin Time (PTT) within normal limits (±15%).

- Disease must be encompassed in a reasonable SBRT "portal" as defined by the treating
radiation oncologist

Exclusion Criteria:

- Ineligible Histology including non-adenocarcinomas, adenosquamous carcinoma, islet
cell carcinomas, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal
carcinomas, distal bile duct and ampullary carcinomas

- Patients must not have received prior pancreatic surgery, radiation therapy,
chemotherapy or any investigational therapy for pancreatic cancer.

- Patients with tumors extending or invading duodenum or gastric are not eligible.

- Evidence of distant metastasis on upright chest x-ray, CT or other staging studies

- Subjects with recurrent disease are not eligible

- Prior radiation therapy to the upper abdomen or liver at the discretion of the
treating radiation oncologist could impair delivery of the prescribed radiation
treatment

- Patients with scleroderma, ulcerative colitis or other systemic conditions deemed
risky for radiation treatment. Therefore, will be excluded.

- Prior chemotherapy

- Subjects in their reproductive age who are breast feeding or have a positive pregnancy
test

- Any co-morbid condition such as but not limited to congestive heart failure, cardiac
arrhythmia or psychiatric illness of sufficient severity to limit full compliance with
the protocol per assessment by the individual treating physician

- Concurrent active infection

- No prior malignancy allowed except cervical cancer in situ, adequately treated basal
cell or squamous cell carcinoma of skin or treated low risk prostate cancer

- Patient with known historical or active infection with HIV, Hepatitis B or Hepatitis C

- Patient who has undergone recent major surgery, other than diagnostic surgical
procedure within 4 weeks prior to enrollment.

- Patient who has a history of allergy or hypersensitivity to any of the study drugs.

- Patients with a history of interstitial lung disease, history of slowly progressive
dyspnea and unproductive cough, sarcoidosis, silicosis, interstitial pulmonary
fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies

- Patients with greater than grade 2 peripheral neuropathy at the time of enrollment are
not eligible.