A Study of Apatinib in Patients With Advanced Hepatocellular Carcinoma

Randomized, Open-label, Multi-center, Phase II Study of Apatinib in Patients With Advanced Hepatocellular Carcinoma

This phase II trial will be studying how well Apatinib working in patients with Hepatocellular carcinoma.

Inclusion Criteria:

• Histologically or cytologic confirmed advanced hepatocellular carcinoma
• Patients who are unable to or unwilling to undergo surgery or interventional procedures via hepatic artery, or patients who have relapsed/progressed after surgery or interventional procedure via hepatic artery for ≥ 4 weeks and are unable to use sorafenib.
• Life expectancy of more than 12 weeks.
• ECOG performance scale 0 - 2.
• Child -Pugh score A，BCLC stage B or C.
• At least one therapy naïve measurable lesion (larger than 10 mm in diameter by spiral CT scan, conforming to RECIST 1.1).
• Have not received systemic chemotherapy or molecular targeted therapy. At least 4 weeks must have elapsed for patients who have previously underwent radiotherapy or surgery, and all the adverse drug reactions (ADRs) or wounds have completely healed. At least 6 months must have elapsed for patients who have received adjuvant chemotherapy.
• Adequate organ functions (hemoglobin≥ 90g/L ,platelets ≥80 × 109/L, neutrophil≥ 1.5 × 109/L, albumin ≥ 29 g/L, Plasma creatinine ≤ 1.5 × ULN , ALT and AST< 5 × ULN; TBIL ≤ 1.5 × ULN.
• Signed and dated informed consent.Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.

Exclusion Criteria:

• Pregnant or lactating women.
• Patients with known intrahepatic cholangiocarcinoma, mixed hepatocellular carcinoma, and fibrolamellar hepatocellular carcinoma; other malignancies previously or currently, except for cured skin basal cell carcinoma and cervical carcinoma in situ.
• Dysphagia, chronic diarrhea, and intestinal obstruction, which significantly affect drug intake and absorption.
• Evidence of CNS metastasis.
• Subjects with hypertension which cannot be well controlled by antihypertensives; grade II or greater myocardial ischemia or myocardial infarction, poorly controlled arrhythmia, and cardiac insufficiency grades III to IV according to NYHA criteria; cardiac color Doppler ultrasound examination: LVEF (left ventricular ejection fraction) of < 50%.
• Subjects with abnormal coagulation functions, and the tendency of bleeding or those who are currently treated by a thrombolytic or anticoagulant therapy.
• Definite concern of gastrointestinal hemorrhage, and history of gastrointestinal hemorrhage within 6 months.
• Patients with symptomatic ascites requiring therapeutic paracentesis or drainage, or with a Child-Pugh score of ≥ 2.