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

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.