Combined Radiotherapy and Sorafenib in Patients With Hepatoma

Inclusion Criteria:

1. Patients with unresectable hepatoma with transarterial embolization (TAE) failure or who are not suitable for TAE.
2. Age: 20 ~ 69 years.
3. ECOG 0 or 1.
4. Life expectancy of at least 12 weeks.
5. Child-Pugh A or B (preferentially score ≦ 7).
6. Cancer of the Liver Italian Program (CLIP) score ≦ 3.

7. Pretreatment liver function test and renal function test:

   • Total bilirubin < 1.5 times the upper limit of normal (ULN)≦ 3.0(ULN)in patients treated by biliary drainage for obstructive jaundice.
   • GOP/GPT ≦ 5 X of upper limit of normal range.
   • Alkaline phosphatase ≦ 4X of upper limit of normal range.
   • Prothrombin time/partial prothrombin time < 1.5 X of ULN.
   • Serum Creatinine ≦ 1.0 x ULN.

8. Pretreatment blood count:

   • Hemoglobulin ≧ 9 g/dl.
   • Absolute neutrophil count ≧ 1500/mm3.
   • Platelet count ≧ 100,000/mm3.
9. Subjects with at least one uni-dimensional or bi-dimensional measurable lesion. Lesion must be measured by CT scan or MRI.
10. Patients must fully recover from prior therapy that given > 4 weeks before enrolment.11. Signed informed consent must be obtained prior to any study related procedures.

Exclusion Criteria:

1. Child-Pugh C
2. CLIP score ≧ 4
3. Patients with evidence of extrahepatic or metastatic disease
4. Patients with evidence of massive ascites
5. Patients receiving previous irradiation to liver
6. Patients with previous use of Thalidomide less than 6 months from entering of the study
7. History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrythmias requiring anti-arrythmic therapy (beta blockers or digoxin are permitted)
8. Active clinically serious infections ( > grade 2 CTC version 2)
9. Patients undergoing renal dialysis
10. Patients with evidence or history of bleeding diathesis
11. Prior treatment with EGFR TKIs or VEGFR TKIs
12. Hypertension uncontrolled by medical therapy
13. Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper.
14. Chemotherapy or immunotherapy or other systemic anti-cancer therapy within 4 weeks (6 weeks for nitrosoureas, mitomycin and suramin)
15. Major surgery within 4 weeks of start of study
16. Concomitant treatment with strong CYP3A4 inducers or inhibitors
17. Investigational drug therapy outside of this trial during or within 4 weeks of study entry
18. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
19. Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation, including the 30 days period after last study drug dosing.
20. Pregnant or breast-feeding patients
21. Known or suspected allergy to the investigational agent or any agent given in association with this trial
22. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry
23. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
24. Patients with seizure disorder requiring medication
25. History of organ allograft
26. Use of biologic response modifiers, such as G-CSF, within 3 week of study entry
27. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
28. Autologous bone marrow transplant or stem cell rescue within 4 months of study
29. Patients unable to swallow oral medications