Phase I-II to Evaluate Efficacy/Safety of Sorafenib+Gemcitabine+Radiotherapy in Locally Advanced Pancreatic Carcinoma

Inclusion Criteria:

1. -Patients with histological or cytological confirmed locally advanced pancreatic adenocarcinoma pancreatic carcinoma or metastatic pancreatic carcinoma for phase I.
2. -Patients with measurable (according to RECIST) disease.
3. -Male or female patients > or = 18 years old
4. -ECOG 0-1
5. -Adequate bone marrow, liver , and renal function: Absolute neutrophil count ( ANC) >= 1,500/mm3 Platelets> or = 100,000/µl Hemoglobin >=9.0 g/dl Total bilirubin < 1.5 x the upper limit of normal. ALT and AST <= 2.5 x upper limit of normal ( <= 5X upper limit of normal for patients with liver involvement ) Serum creatinine <= 1.5 times x the upper limit of normal. Patients with creatinine clearance >= 45mL/min PT( prothrombin time ) or INR( international normalized ratio ) and PTT ( partial thromboplastin time ) < =1.5 x
6. -Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least six months after the last administration of sorafenib
7. -Signed informed consent prior to any study specific procedures

Exclusion Criteria:

1. -Patients with previous treatment for pancreatic carcinoma
2. -PTV ( planning target volume ) >500 cm3 or 5 cm (maximum diameter)
3. -Patients with known or suspected allergy to iodated contrasts or renal impairment which prevents from radiological tests.
4. -Pregnant or nursing patients. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
5. -General medical or psychological conditions that would preclude appropriate informed consent or compliance with the protocol.
6. -Previous cancer that is distinct in primary site or histology from NSCLC except cervical cancer in-situ, treated basal cell carcinoma, superficial bladder tumors (Ta and Tis) or any cancer curatively treated > 3 years prior to study entry
7. -Concurrent treatment with other experimental drugs (within 30 days prior to study entry).
8. -Concurrent treatment with other anti-cancer therapy.
9. -Therapeutic anticoagulation with Vitamin K antagonists such as warfarin or with heparins or heparinoids. Low dose warfarin is permitted if INR is <1.5 . Low dose aspirin is permitted .
10. -Patients with any medical condition which could jeopardize their safety while his participation in the study .
11. -Significant weight loss (> or equal 10% body weight during preceding 6 weeks)
12. -Major surgery within 3 previous weeks, or laparoscopic biopsy or significant traumatic injury within 2 weeks of prior to first dose of study drug.
13. -Known or suspected allergy to sorafenib or any agent given in the course of this trial .
14. -Patients with evidence or history of bleeding diathesis or coagulopathy
15. -Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months
16. -Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg, despite optimal medical management
17. -Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina or new-onset angina (began within the last 3 months) or myocardial infarction within the last 6 months
18. -Patients with Child-Pugh class C hepatic impairment
19. -Patients with severe renal impairment (calculated creatinine clearance of < 30 ml/min) or who require dialysis
20. -Active clinically serious infections > CTCAE Grade 2
21. -Serious, non-healing wound, ulcer, or bone fracture
22. -Patients with concomitant ketoconazole, itraconazole,ritonavir,rifampicin or St. John's Wort (Hypericum perforatum).
23. -Known brain metastasis. Patients with neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasis
24. -Any instable condition that may interfere with the patients participation in the study