Phase I Study of Gemcitabine, Sorafenib and Radiotherapy in Patients With Unresectable Pancreatic Cancer

Inclusion Criteria: 1. Histologically/pathologically confirmed locally advanced unresectable or borderline unresectable pancreatic cancer \& no evidence of metastatic disease. Diagnosis of locally advanced unresectable pancreatic cancer is based on assessment by dual-phase CT scan and/or endoscopic ultrasound (EUS). 2. Age ≥ 18 years at time of consent 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 4. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) \& obtained by dual-phase CT scan within 14 days prior to being registered for protocol therapy. 5. Tumor size ≥ 2 cm on dual-phase computed tomography scan. 6. Adequate organ function documented within 14 days of registration as laboratory tests per protocol. 7. Patients with biliary obstruction must have percutaneous transhepatic drainage or endoscopic stent placement prior to starting study treatment 8. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Women of childbearing potential \& men must agree to use adequate contraception (barrier method of birth control) prior to study entry \& for the duration of study participation \& for at least three months after the last administration of sorafenib. 9. Ability to understand \& the willingness to sign a written informed consent. A signed informed consent \& authorization for release of personal health information must be obtained prior to any study specific procedures. 10. Patients with a history of malignancy are eligible provided they have been curatively treated \& demonstrate no evidence for recurrence of that cancer. Exclusion Criteria: 1. Prior treatment with Gemcitabine within 6 months prior to registration. 2. Prior treatment with Sorafenib or other Ras or VEGF pathway inhibitors. 3. Prior radiation therapy to the upper abdomen 4. Evidence of metastatic disease 5. Clinical evidence of duodenal mucosal invasion by tumor (as documented by endoscopy or endoscopic ultrasound). 6. Minor surgical procedure (e.g. fine needle aspiration or needle biopsy) within 14 days of study registration. 7. Major surgical procedure, significant traumatic injury, or serious non-healing wound, ulcer or bone fracture within 21 days of study registration; investigator has to document adequate healing has occurred prior to study registration. 8. Any of the following within 6 months prior to study drug administration: severe/unstable angina (anginal symptoms at rest), new onset angina (began within the last 3 months) or myocardial infarction, congestive heart failure, cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. 9. History of thrombotic or embolic events such as cerebrovascular accident or transient ischemic attack within the past 6 months. History of aneurysm or arteriovenous malformation. 10. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C. 11. Active clinically serious infection \> Common Toxicity Criteria for Adverse Effects (CTCAE) grade 2. 12. Receipt of any investigational agent within 4 weeks of study registration. 13. Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management. 14. Pulmonary hemorrhage/bleeding event \> CTCAE Grade 2 within 4 weeks of study registration 15. Any other hemorrhage/bleeding event \> CTCAE Grade 3 within 4 weeks of study registration 16. Evidence or history of bleeding diathesis or coagulopathy. 17. Chronic, daily treatment with aspirin or other nonsteroidal anti-inflammatory medications. 18. Use of St. John's Wort, rifampin (rifampicin), ketoconazole, itraconazole, ritonavir or grapefruit juice. 19. Known or suspected allergy to Sorafenib or any agent given in the course of this trial. 20. Any condition that impairs patient's ability to swallow whole pills. 21. Any malabsorption problem. 22. Other severe, acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results \& in the judgment of the investigator would make the patient inappropriate for entry into this study. 23. History of collagen vascular disease. 24. Any contraindication to undergo magnetic resonance imaging