TACE Plus Recombinant Human Adenovirus for Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to determine if TACE plus Recombinant Human Adenovirus Type 5 Injection will improve outcome in patients with advanced hepatocellular carcinoma (HCC) not amenable to surgery or local ablative therapy.

Detailed Description
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Transarterial chemoembolization (TACE) is currently one of the mainstays of palliative treatments worldwide for patients with unresectable Hepatocellular Carcinoma(HCC).However, the long term outcomes were generally poor for HCC patients treated with TACE. Recombinant Human Adenovirus Type 5, an E1B gene deleted adenovirus, is known to have a significant antitumor activity. In addition, local injection of recombinant human adenovirus type 5 can enhance the effect of antitumor therapies (chemotherapy and radiotherapy). The hypothesis is that patients with unresectable HCC may benefit from recombinant human adenovirus type 5 in combination with TACE.

Official Title
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Phase Ⅲ Trial of Transcatheter Arterial Chemoembolization(TACE) Plus Recombinant Human Adenovirus Type 5 Injection for Unresectable Hepatocellular Carcinoma (HCC)

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Recombinant Human Adenovirus Type 5 Injection
* Procedure: Transartery Chemoembolization


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: TACE Only<br>TACE with chemothrapy drugs (E-ADM 50mg, Lobaplatin 50 mg, MMC 6mg)and followed with embolization with lipiodol or/and polyvinyl alcohol particles. | Procedure: Transartery Chemoembolization<br>* Transartery chemoembolization with chemothrapy drugs (E-ADM 50mg, Lobaplatin 50 mg, MMC 6mg)and followed with embolization with lipiodol or/and polyvinyl alcohol particles.<br>|
| Experimental: TACE Plus Adenovirus<br>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) | Drug: Recombinant Human Adenovirus Type 5 Injection<br>* 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<br>Procedure: Transartery Chemoembolization<br>* Transartery chemoembolization with chemothrapy drugs (E-ADM 50mg, Lobaplatin 50 mg, MMC 6mg)and followed with embolization with lipiodol or/and polyvinyl alcohol particles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival time |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events | 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 ) | 30 days | 
| Tumor response | Tumor response based on modified RECIST | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TACE, Carcinoma,Hepatocellular, Liver Neoplasms, overall survival, Recombinant Human Adenovirus Type 5 Injection