Safety profile and to determine maximum tolerated dose (MTD) / Recommended Dose (DR) of Sorafenib in combination with Gemcitabine and Radiotherapy~Definition of maximum tolerated dose (MTD):~The MTD is defined as the highest dose level which can be given to 6 patients such that no more than 1 patient experiences a DLT .~Definition of Recommended Dose (DR):~Is the MTD~Definition of Dose-limiting toxicity (DLT):~DLT will be defined as any of the following occurring during the period of treatment and regarded as related to the combination regimen.~Grade 4 thrombocytopenia persisting greater than 4 days, or with bleeding requiring platelet transfusion~Grade 4 neutropenia lasting more than 7 days~Febrile neutropenia (≥ 38.5oC) with an absolute neutrophil count ≤ 1000/mm3~Any grade 3 or 4 non-hematologic toxicity related to the combination [occurring despite optimal supportive care, if applicable] except hyperglycemia, hypoglycemia, deep venous thrombosis, or hyperbilirubinemia secondary to stent malfunction.~Hypertension that is symptomatic and not managed by maximal use of three different classes of antihypertensives, or any episode of malignancy hypertension~(Detailed Dose Modifications and G-CSF use in case of febrile neutropenia will be outlined in the full protocol version)~Phase II~Primary objective:~Activity profile evaluating Progression-free rates (PFR) at 6 months~Secondary objective:~Response rate Overall survival Toxicity profile
Phase I: Safety profile and to determine maximum tolerated dose (MTD) / Recommended Dose (DR) of Sorafenib in combination with Gemcitabine and Radiotherapy~Phase II: Activity profile evaluating Progression-free rates (PFR) at 6 months, Response rate, Overall survival, Toxicity profile