Efficacy and Safety of TACE on Downstaging Hepatocellular Carcinoma Beyond UCSF Criteria;

Efficacy and Safety of TACE on Downstaging Hepatocellular Carcinoma Beyond UCSF Criteria: a Multi-center, Randomized, Parallel-controlled Study

This is a multicenter, randomized, parallel controlled study to determine the efficacy and safety of transcatheter arterial chemoembolization (TACE) on downstaging hepatocellular carcinoma beyond University of California, San Francisco (UCSF) criteria.

Inclusion Criteria:

1. 18 to 70 years of age, of any sex;
2. Patients who have histopathological or cytological proof of hepatocellular carcinoma (HCC) or meet the diagnostic criteria of Diagnosis, management, and treatment of hepatocellular carcinoma(V2017);
3. Beyond UCSF criteria: Diameter of single HCC lesion is between 6.5 cm and 10 cm; The number of tumors ≤3 with the maximum diameter of 4.5-5cm and the total diameter ≤10cm; Multiple HCC lesions ≤5 nodules, each lesion diameter≤4 cm with a total diameter ≤10 cm. Patients cannot be treated with resection or liver transplantation;
4. Patients with stage Ib，IIa，IIb in China liver cancer staging (CNLC) ;
5. Child-Pugh's grade A or B (no more than 7 score);
6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1;
7. Patients with hepatitis B virus (HBV) infection should receive routine antiviral therapy;
8. The function of main organs is normal and meet the following criteria:

1) Outcome of blood routine must meet the following criteria (No blood transfusion or blood products were performed within 4 days, and no g-CSF or other hematopoietic stimulants were used for correction): i. Hemoglobin(HB)≥90 g/L; ii. Absolute neutrophil count (ANC)≥1.5×109/L； iii. Platelet (PLT)≥80×109/L; 2) Outcome of hemal biochemistry examination meet the following criteria: i. Albumin (ALB) ≥29 g/L; ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)<2.5 × upper limit of normal (ULN); iii. Total bilirubin (TBIL) ≤2 × ULN; iv. Serum creatinine (SCr) ≤1.25 × ULN, or endogenous creatinine clearance > 45 ml/min (Cockcroft-Gault formula); 3) Patients who have normal livers with an Remnant Liver Volume (RLV)/Standard Liver Volume(SLV) >20% ; Patients who have cirrhosis with an RLV/SLV>40%; 9. Life expectancy of > 3 months; 10. Patients volunteered to participate in this study and signed informed consent, with good compliance.Exclusion Criteria.

Exclusion Criteria:

1. Patients with extrahepatic metastasis or main portal vein /main hepatic vein invasion;
2. Patients with diffuse liver cancer;
3. Patients with myocardial ischemia, myocardial infarction or poor controlled arrhythmia (including QTc≥470 ms) beyond stage Ⅱ; according to New York Heart Association (NYHA) standard, patients with heart failure in stage Ⅲ～Ⅳ; patients with an left ventricular ejection fraction(LVEF) <50%;
4. Abnormal coagulation （International Normalized Ratio(INR)>1.5, Prothrombin Time(PT)>ULN+4s or Activated Partial Thromboplastin Time (APTT) >1.5 ×ULN）,or patients with bleeding tendency or undergoing thrombolytic or anticoagulant therapy;
5. Patients unsuitable for the study in the opinion of the Investigator;
6. Pregnant or breastfeeding women; women of childbearing ages unless using effective contraception;
7. Patients with mental disorders or history of abuse of psychotropic substances;
8. Infection with human immunodeficiency virus (HIV);
9. A history of liver resection, liver transplantation, interventional therapy, or combined with other malignant tumors;
10. Patients with active infection;
11. Patients with contraindications to TACE or epirubicin;
12. Floating population or with poor compliance;
13. Patients in other clinical trials conducting with experimental-related drugs or devices within 4 weeks.