Efficacy and Safety of Apatinib Combined With TACE in Patients With Hepatocellular Carcinoma

Inclusion Criteria:

* Age: 18-70 years old;Estimated survival time≥12 weeks
* Histologicaly and cytologicaly diagnosed as Hepatocellular carcinoma of the liver ( HCC ) and with At least one imaging examination of measurable lesions (RECIST), CT or MR scan Long diameter of tumor ≥ 10 mm.Target lesion without Local treatment
* Child-pugh liver function Rating: A level, B level
* BCLC Staging as B / C period
* ECOG 0-1
* Have progressed after at least twice TACE
* The main organ function is normal, and meet the following standards:(1)The standard of blood routine examination should be consistent: HB≥90 g/L, ANC≥1.5×10\^9/L, PLT≥60×10\^9/L; (2)Biochemical tests should meet the following criteria: ALB ≥29 g/L；TBIL\<2'ULN, ALT and AST\<5'ULN,Cr ≤ 1.5\*ULN
* Fertile woman must perform a pregnancy test (serum or urine) 7 days before screened, or voluntarily adopt proper methods of contraception during the observation period and 8 week after the last given apatinib. For man, surgical sterilization should be performed, or voluntarily adopt proper methods of contraception during the observation period and 8 week after the last given apatinib
* Patients voluntarily entered the study and signed informed consent form (ICF).

Exclusion Criteria:

* Received Any local treatment other than TACE (including but not limited to surgery, radiotherapy, hepatic arterial embolization, hepatic arterial infusion, radiofrequency ablation, cryoablation, or percutaneous ethanol injection) within four weeks before randomization
* Participated in other cancer drug clinical trials within four weeks before randomization
* hepatobiliary cell carcinoma and mixed cell carcinoma are known; previous ( 5 year) or at the same time suffering from other incurable malignancies, except for the cured basal cell carcinoma of the skin and cervical carcinoma in situ
* have received or Prepared for liver transplantation
* A serous cavity effusion (including hydrothorax, ascites, pericardial effusion) with local symptoms requiring local treatment; or Child-Pugh\>2；
* Patients with uncontrol hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, despite optimal drug therapy)
* Suffering from coronary heart disease, arrhythmia or grade II (including QTc prolongation \> 450 ms male, female, 470 MS) and Cardiac insufficiency
* According to NYHA standard, III \~ IV cardiac insufficiency, or heart colour to exceed revealed left ventricular ejection fraction (LVEF) \< 50%
* There are several factors that affect oral medicine,such as unable to swallow, chronic diarrhea and intestinal obstruction
* Before randomization within 6 months had significant bleeding clinical significance or definite bleeding tendency, such as gastrointestinal bleeding, bleeding gastric ulcer, baseline fecal occult blood and above, or suffering from vasculitis
* History of abdominal fistula, gastrointestinal perforation or abdominal abscess within 28 days before randomization
* Abnormal coagulation (INR\>1.5 or PT\>ULN+4, or APTT\>1.5 ULN), bleeding tendency or receiving coagulation therapy
* Central nervous system with symptoms of metastasis
* there is typical interstitial pneumonia or pulmonary fibrosis
* Patients with a history of psychiatric drug abuse and can not be prevented or have mental disorders
* before participating in the study 7 days use strong-effect in CYP3A4 inhibitor therapy, or prior to participating in the study 12 days use the strong-effect in CYP3A4 inducer Therapy
* pregnant or lactating women who are not willing or unable to take effective contraceptive measures
* A history of mental illness, or psychotropic substance abuse
* Patients with allergies to research drugs
* Other patients who were considered unsuitable for inclusion by physicians.