Study of Apatinib After Systemic Therapy in Patients With Hepatocellular Carcinoma(AHELP)

Inclusion Criteria

• ≥ 18 years old.
• Conform to the clinical diagnosis standard strictly or histological or cytological confirmation of HCC (hepatocellular carcinoma) who cannot benefit from treatments of established efficacy with higher priority such as resection, local ablation,and with at least one uni-dimensional measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to RECIST 1.1.
• Failure or intolerance to prior treatment with chemotherapy and/or targeted therapy (Failure is defined as documented radiological progression according to the radiology charter. Intolerance is defined as ≥ grade 4 hematologic toxicities, ≥ grade 3 non-hematologic toxicities ≥ grade 2 heart, liver or kidney damage).
• Systemic therapy must have been completed ≥2 weeks before randomization (AEs due to prior treatment ≤ grade 1).
• Liver function status Child-Pugh Class A or B (score≤7).
• Barcelona Clinic Liver Cancer stage Category B or C.
• Eastern Cooperative Oncology Group Performance Status of 0 or 1 within 1 week before randomization.
• Life expectancy of at least 12 weeks.
• HBV DNA ≤ 2000IU/ml or 1×10E+4 copy/ml.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory tests conducted within 1 week before randomization.

HB ≥ 90g/L; ANC≥1.5×10E+9/L; PLT≥80×10E+9/L; ALB ≥ 29g/L; ALT and AST 2.

• Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg).
• Suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female≥ 470 ms).
• Grade III-IV cardiac insufficiency, according to NYHA criteria or echocardiography check: LVEF 1.5 x ULN, or PT > ULN +4 seconds), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy;
• Occurrence of central nervous system metastatic or known brain metastatic;
• Objective evidence of previous or current pulmonary fibrosis history, interstitial pneumonia, Pneumoconiosis, radiation pneumonitis, drug-related pneumonia, Pulmonary function damaged seriously etc.
• Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g.
• Received powerful inhibitor of CYP3A4 within 7 days or powerful inducer of CYP3A4 within 12 days before randomization.
• Pregnant or breast-feeding women; patients with fertility will not or there is no way to adopt effective contraceptive measures.
• Mental disorders history, or Psychotropic drug abuse history.
• Patients who has bone metastasis, has received Palliative radiotherapy (radiotherapy area > 5% marrow area).