A Single Center Study of Donafenib Combined With PD-1 + TACE in the First-line Treatment of aHCC

Prior treatment

• Hepatocellular carcinoma recurrence within 2 years after radical resection or ablation;
• Esophageal and/or gastric varices bleeding within 4 weeks prior to initiation of study treatment;
• Patients who received liver transplant surgery, prior systemic therapy (chemotherapy, targeted therapy or immunotherapy) or palliative local treatment ≥2 times for HCC；

Other illness

• History of malignancy other than HCC within 5 years;
• Presence of uncontrolled hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion, or pericardial effusion;
• History of organ and cell transplantation；
• Active severe infection;
• Autoimmune disease or immune deficiency;
• Severe organ (heart, kidney) dysfunction;

Other

• Pathologically confirmed hepatocellular carcinoma intrahepatic cholangiocarcinoma (HCC-ICC) mixed or fibrolamellar hepatocellular carcinoma;
• The presence of a tumor thrombus in the main portal vein, biliary tract tumor thrombus, inferior vena cava tumor thrombus, or extrahepatic metastasis;
• TACE contraindications identified by the investigator;
• Pregnant or breastfeeding women, and women or men with fertility who are unwilling or unable to take effective contraceptive measures;
• Unable to follow the research protocol for treatment or scheduled follow-up; Any other researcher who thinks they cannot be included.

• Patients voluntarily enter the study and sign informed consent form (ICF);
• Age ≥ 18 years and ≤ 75 years, and there is no limit on the gender;
• Clinically or histologically diagnosed as unresectable HCC;
• There is at least one measurable lesions that meet the mRECIST standard;
• Child-pugh classification A or B (score≤7);
• ECOG : 0 \~ 1 ;
• The number of intrahepatic tumors ≤ 10 and the maximum tumor diameter ≤ 10cm;
• Previous TACE treatment ≤ 1 time;
• Life expectancy ≥ 3 months;
• For patients with HBV infection, if HBV-DNA is≥10\^4copies/ml within 14 days before enrollment, they should take antiviral treatment first, reduce 1 log or reduce to \<10\^4copies/ml before entering the study, and continue antiviral treatment and monitor liver function and serum HBV-DNA levels;
• Baseline blood routine and biochemical indexes meet the following criteria within 14 days before treatment:
  • Blood routine examination criteria must be met: (no blood transfusion within 14 days)
  • HB≥90g/L；
  • ANC≥1.5×10\^9/L；
  • PLT≥70×10\^9/L.
  • Biochemical tests are subject to the following criteria:
  • BIL \<1.25xULN ；
  • ALT and AST\<5xULN；
  • Serum creatinine. Less than 1.5 times the upper limit of normal value, Endogenous creatinine clearance\>50ml/min ( Cockcroft-Gault formula)；
  • Albumin≥28g/L；
  • Electrolytes (phosphorus, calcium, magnesium, potassium) ≥ LLN;
  • Urine protein \<2+ or 24-hour urine protein quantitative detection ≤1.0 g/L.
  • Blood coagulation indexes are subject to the following criteria:
  • Prothrombin time (PT) and international normalized ratio (INR) ≤1.5 × ULN;
  • Activated partial thromboplastin time（APTT）≤1.5 × ULN.
• The serum pregnancy test results of female patients with fertility (referring to premenopausal or non surgical sterilization) must be negative within 14 days before enrollment.