Randomized Phase I/II of RAD001 in Advanced Hepatocellular Carcinoma (HCC)

Inclusion Criteria:

• Patients with measurable, metastatic or locally advanced HCC that are not feasible to have or have failed to prior local therapy (including surgical resection, transarterial chemoembolization and/or alcohol injection) are eligible.
• The diagnosis of HCC should be established either by cyto/histology; or, by characteristic imaging studies (have to including angiography) plus serum level of AFP equal to or more than 400 ng/mL in patients with cirrhosis of the liver and/or chronic viral hepatitis B or C infection.
• Patients must be equal to or more than 20 years of age and equal or less than 75 years of age.
• Patients must have a performance status of ECOG score equal to or less than 2.
• Patients must fulfill all of the following criteria: Child-Pugh's Score equal to or less than 9; serum total bilirubin level is equal to or less than 2.0 mg/dL; serum ALT level (GPT) equal to or less than 3.0 x upper normal limit; platelet are equal to or more than 50,000 / uL; WBC are equal to or more than 3,000 / uL.
• Serum creatinine equal to or less than 2.0 x upper normal limit.
• Life expectancy equal to or more than 12 weeks.
• Signed informed consent.
• Sexually active patients, in conjunction with their partner, must practice birth control during, and for 2 months after therapy.
• Female patients at child-bearing age must have negative pregnancy test.
• No known HIV infection.

Exclusion Criteria:

• Patients with diseases which require concurrent usage of glucocorticosteroid or immunosuppressant agent(s) are not eligible.
• Patients with concomitant active secondary malignancies, except for surgically cured carcinoma in situ of the cervix and basal or adequately treated squamous cell carcinoma of the skin, or disease-free of malignancies < 3 years before the study, are not eligible.
• Patients with active infection are not eligible.
• Patients who received other rapamycin analogs before are not eligible.
• Patients with severe cardiopulmonary diseases (including history of stable, effort-induced or unstable angina pectoris or myocardiac infarction) and other systemic diseases under poor control are not eligible.
• Patients with history of psychiatric disorder are not eligible.
• Patients with brain metastases are not eligible.
• Patients who received surgery, radiotherapy except to bone, chemotherapy, immunotherapy, or other investigational drug within 4 weeks before initiating study are not eligible.
• Patients who are pregnant, breast-feeding or not using appropriate birth control during the course of the study are not eligible.
• Patients with significant concomitant disease that will be aggravated by the investigational drug are not eligible.
• Patients on active treatment with inhibitors or inducers of P-glycoprotein, CYP3A4 and CYP3A5 are not eligible; a minimal of 2 weeks wash-out period will be required after stop such medications.