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
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
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
300 mg/m2/one per week, i.v., during 5 weeks.
1.8 Gy/day 5 days per week during 5 weeks (total dose 45Gy)
200-800 mg/day p.o. during 5 weeks
Hospital de La Santa Creu I Sant Pau
Barcelona, Barcelona, Spain
Hospital Clinic I Provincial
Barcelona, Barcelona, Spain
Hospital Universitario La Paz
Madrid, Madrid, Spain
Hospital Universitario La Fe
Valencia, Valencia, Spain
SAFETY
Time frame: End of Study
EFFICACY
Time frame: End of Study
TO DETERMINE MTD
Time frame: Treatment (5 weeks)
RESPONSE (ACCORDING TO RECIST)
Time frame: End of Study
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