A Study of Apatinib for Advanced Hepatocellular Carcinoma Patients After First-line Treatment Failure

Inclusion Criteria:

• Patients with a histologic or cytologic diagnosis of hepatocellular carcinoma, imagingdiagnosis should be compatible with chinese standard for diagnosis and treatment ofprimary liver cancer (Edition 2011)

• Have progressed after systematic chemotherapy/target therapy, or cannot tolerated withfirst-line treatment, and have at least one measurable lesion. according to RECIST 1.1, the long diameter of measurable lesion should be more or equal than 10mm, or theshort diameter of a enlarged lymph node should be more or equal than 15mm, the maximumdiameter of a viable tumor should be no more than 15cm

• The previous chemotherapy and the present trial registration must be at least 2 weeksapart. And they must have recovered from any toxicity of a previous chemotherapy

• Patients with Child Pugh Class A & B disease are eligible for the study

• Patients with Barcelona Clinic Liver Cancer stage B or C are eligible for the study

• Eastern Cooperative Oncology Group performance score (PS): 0-2

• Life expectancy of at least 12 weeks

• Hepatitis B virus DNA<2000 IU/ml

• Adequate organ function meeting the following:

• Bone marrow: absolute neutrophil count ≥1.5×109/L (1500/mm3); platelet ≥ 75×109/L; hemoglobin ≥9 g/dL

• Liver: Serum bilirubin ≤ 1.5 ×ULN, AST and ALT ≤ 5 ×ULN, ALB ≥ 29 g/L

• Kidney: Cr ≤1.5 ×upper limit of normal

• Within 7 days prior to the start of therapy, women of child-bearing potential mustundergo a pregnancy test, which must be negative; men of child-bearing potential:contraceptive measures must be adopted during treatment and within 8 weeks afterward

• Subjects who understand and voluntarily signed a written informed consent form

Exclusion Criteria:

• Diagnosed with cholangiocellular carcinoma, mixed cell carcinoma and fibrolamellarhepatocellular carcinoma

• History of other malignancy within 5 years except for non-melanoma skin cancer, cervixin situ carcinoma

• Prepared for liver transplantation

• Patients with contraindications (active bleeding, ulcers, intestinal perforation,intestinal obstruction, within 30 days after major surgery, uncontrolled high bloodpressure medication, III-IV level cardiac insufficiency, severe liver and kidneydysfunction)

• A previous history of Interstitial pulmonary disease, drug-induced interstitialdisease, radiation pneumonitis requiring hormonal therapy or active interstitial lungdisease with any clinical evidence

• Use of CYP3A4 inhibitor within 7 days or CYP3A4 inducer within 12 days prior toenrollment

• Patients with central nervous system metastases or brain metastasis

• Previous definite diagnosis of neuropsychiatric disturbances, including epilepsy ordementia

• Pregnant or lactating women

• Patients with bone metastasis received palliative radiation within 4 weeks prior toenrollment