TACE Plus Recombinant Human Adenovirus for Hepatocellular Carcinoma

• Number of adverse events [ Time Frame: 30 days ]
  Number of adverse events, and number of patients who developed adverse event. Postoperative adverse events were graded based on the Common Terminology Criteria for Adverse Events ( CTCAE )
• Tumor response [ Time Frame: 12 weeks ]
  Tumor response based on modified RECIST

• Drug: Recombinant Human Adenovirus Type 5 Injection
  After identifying the target artery of HCC, Recombinant Human Adenovirus Type 5 Injection（15.0*1011vp：0.5ml*3） will be first infused through the target artery
• Procedure: Transartery Chemoembolization
  Transartery chemoembolization with chemothrapy drugs (E-ADM 50mg, Lobaplatin 50 mg, MMC 6mg)and followed with embolization with lipiodol or/and polyvinyl alcohol particles.

• Active Comparator: TACE Only
  TACE with chemothrapy drugs (E-ADM 50mg, Lobaplatin 50 mg, MMC 6mg)and followed with embolization with lipiodol or/and polyvinyl alcohol particles.
  Intervention: Procedure: Transartery Chemoembolization
• Experimental: TACE Plus Adenovirus
  After identifying the target artery of HCC, Recombinant Human Adenovirus Type 5 Injection（15.0*1011vp：0.5ml*3） will be first infused through the target artery of HCC patient and followed with chemothrapy drugs (E-ADM 50mg, Lobaplatin 50 mg, MMC 6mg) and lipiodol emulsion or/and polyvinyl alcohol particles(dependent on the tumor size) Procedure: TACE (Transcatheter arterial chemoembolization)
  Interventions:

  • Drug: Recombinant Human Adenovirus Type 5 Injection
  • Procedure: Transartery Chemoembolization

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Inclusion Criteria:

• Patients newly diagnosed as HCC according to European Association for Study of the Liver criteria.
• BCLC stage A or B
• Child-Pugh class A or B (Child-Pugh score 7)
• ECOG performance status of 0

• Patients must have at least one tumor lesion that meets both of the following criteria:

  • The lesion can be accurately measured in at least one dimension according to RECIST criteria
  • The lesion has not been previously treated with surgery, radiation therapy, radiofrequency ablation, percutaneous ethanol or acetic acid injection, or cryoablation.
  • Patients who have received previous local therapy treatments (RFA, PEI, cryoablation, surgery, resection) to non-target lesions are eligible
  • Local therapy must have been completed at least 4 weeks prior to baseline scan.
• Haematology:Absolute neutrophil count (ANC) > 1 x 109/L, Platelet count > 40 x 109/L, Haemoglobin > 9 g/dL (may be transfused to maintain or exceed this level) Prothrombin time international normalized ratio < 1.5
• Biochemistry:Total bilirubin < 2 mg/dL Serum creatinine < 1.5 x the upper limit of normal
• Ability to understand the protocol and to agree to and sign a written informed consent document

Exclusion Criteria:

• Tumor factors

  • Presence of extrahepatic metastasis
  • Predominantly infiltrative lesion
  • Diffuse tumor morphology with extensive lesions involving both lobes.

• Vascular complications

  • Hepatic artery thrombosis, or
  • Partial or complete thrombosis of the main portal vein, or
  • Tumor invasion of portal branch of contralateral lobe, or
  • Hepatic vein tumor thrombus, or
  • Significant arterioportal shunt not amenable to shunt blockage

• Liver function

  • Advanced liver disease: ascites, hepatic encephalopathy
  • Patients with clinically significant gastrointestinal bleeding within the 30 days prior to study entry.

• Others

  • Renal failure requiring hemo- or peritoneal dialysis
  • Pregnant or lactating women.
  • Active sepsis or bleeding.
  • Hypersensitivity to intravenous contrast agents.
  • The patient has received prior treatment for HCC target lesion.

  • History of cardiac disease

    • Congestive heart failure > NYHA class 2; active coronary artery disease
    • Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
  • Hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management.
  • Serious non-healing wounds (including wounds healing by secondary intention), acute or non-healing ulcers, or bone fractures within 3 months.
  • The patient is, in the opinion of the investigator, unable and / or unwilling to comply with treatment and study instructions.
  • Substance abuse (current), psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
  • Any active clinically serious infections (> grade 2 NCI-CTCAE ver 3.0)
  • HIV infection or AIDS-related illness or serious acute or chronic illness (based on medical history)