Multicenter RCT of ADV-TK Gene Therapy Improving the Outcome of Liver Transplantation for Advanced HCC

Study Overview
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Brief Summary
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Compare the effect of liver transplantation (LT) plus ADV-TK gene therapy versus LT only in advanced primary hepatocellular carcinoma.

Official Title
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Multicenter Randomized Controlled Trial of Adenovirus-mediated Adjuvant Gene Therapy Improving Outcome of Liver Transplantation in Patients With Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: ADV-Tk
* Procedure: LT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 - 65 years of age (Male and Female). Clinical diagnosis of advanced primary hepatocellular carcinoma who could accept liver transplantation. Patients who had unresectable HCC with single tumor diameter > 5 cm and ≤ 10cm; or numbers of multiple tumors >3 and ≤ 5, and the total length of foci diameter ≤ 15 cm. Serum AFP ≤ 10000 ng/ml before liver transplantation. Child-pugh A-B. No metastasis in extrahepatic main vescular and extrahepatic lymph node detected during the operation and no metastasis of other organs. Provide written informed consent before screening. Exclusion Criteria: Metastasis in extrahepatic organs. HCC with Invasion in extrahepatic main vescular and extrahepatic organs. Contraindications of operation of other organ system. Hypersensitivity to adenovirus, GCV or similar drugs. Serious obstacle of the mechanism of coagulation, hemorrhagic tendency, and abnormal coagulation (≥50%). Plan to accept clinical trials of other antitumor drugs. Immunological deficit. HBsAg(+) and HBcAb(+) donor. Unsuitable participate assessed by investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LT-only<br>patients received orthotopic LT and subsequent immunosuppression therapy | Procedure: LT<br>* Orthotopic LT and subsequent immunosuppression therapy<br>|
| Experimental: LT+ADV-TK<br>ADV-TK therapy was administered in addition to orthotopic LT and subsequent immunosuppression therapy | Drug: ADV-Tk<br>* The first ADV-TK dose was administered during the operation; 1.0×10(12) viral particles of ADV-TK in 100 mL of 0.9% saline were injected into peritoneum tissues around the liver. The second and third ADV-TK dose was administered 60 days and 90 days after LT; 1.0×10(12) viral particles of ADV-TK in 100 mL of 0.9% saline were injected into the celiac artery (60 mL) and the superior mesenteric artery (40 mL) via femoral-artery puncture.<br>Procedure: LT<br>* Orthotopic LT and subsequent immunosuppression therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival, PFS | PFS was measured from the day of liver transplantation to objective recurrence (MRI or CT) or HCC-related death, whichever occurred first. | 2-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival, OS | OS was measured from the day of liver transplantation to death. | 1-year | 
| Overall survival, OS | OS was measured from the day of liver transplantation to death. | 2-year | 
| Time of the tumor progression,TTP | TTP was the median period from the day of liver transplantation to objective recurrence (MRI or CT). | 2-year | 
| Median overall survival time |  | 2-year |