Trans-catheter Chemo-embolization Combined With rAd-p53 Gene Injection in Treatment of Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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Treatment options for advanced hepatocellular carcinoma (HCC) are limited due to patients' poor condition, advanced tumor, concomitant intra- and extra-liver diseases, and resistance to both chemo- and radio-therapy. Trans-catheter embolization (TAE) or Trans-catheter chemo-embolization (TACE) is the most widely used locoregional treatment for advanced HCC. But no solid evidences support the beneficial effect of the chemotherapy in TACE. Many advanced HCC patients also can't tolerate the locoregional chemotherapy. The p53 gene has multiple anticancer functions and does not have any of the immune-inhibitory effects of chemo- or radio-therapy. The objectives of this study are to investigate the efficacy and safety usingTAE plus recombinant adenoviral human p53 gene (rAd-p53) in treatment of advanced HCC.

Detailed Description
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Study design: multicenter, open-labeled, active-controlled phase II study Study treatments: TACE combined with rAd-p53 injection vs.TACE. The treatments are given once per 21 days until the disease progression. For the experiment group, 2 X 1000,000,000,000 viral particles of rAd-p53 will be injected into the embolization artery. Study objectives: efficacy and safety of the study treatments Study endpoints: safety (adverse events, vital signs, lab tests, ECG and physical examination) and efficacy (progression-free survival, overall survival, and ECOG PS)

Official Title
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Multicenter, Open-labeled, Controlled Phase II Study: Trans-catheter Chemo-embolization Combined With rAd-p53 Gene Injection in Treatment of Advanced Hepatocellular Carcinoma

Conditions
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Advanced Adult Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: TACE plus rAd-p53 artery injection
* Drug: TACE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histopathologically diagnosed HCC; unresectable; over 18 years old; with an Eastern Cooperative Oncology Group (ECOG) score of 0-2; with Barcelona Clinic Liver Cancer (BCLC) Stage of B or C; with Child-Pugh score A or B; with normal tests of hemogram, blood coagulation, liver and kidney function; 8. signed the informed consent form. Exclusion Criteria: Serious blood coagulation disorder, bleeding tendency, platelet < 6 * 1000000000/L; have serious heart, lung function abnormalities or severe diabetes patients; active infection; liver function Child-Pugh grade C; secondary and diffuse hepatocellular carcinoma patients; extensive metastasis; severe atherosclerosis; AIDS patients; serious thrombotic or embolic events within 6 months; renal insufficiency requiring hemodialysis or peritoneal dialysis; 12. pregnant or lactating women; 13. mental disorder or disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TACE plus rAd-p53<br>TACE plus rAd-p53 artery injection' | Drug: TACE plus rAd-p53 artery injection<br>* Trans-catheter chemo-embolization (TACE) with rAd-p53 injection will be given every 21 days<br>* Other names: no other name;|
| Active Comparator: TACE<br>TACE will be applied alone | Drug: TACE<br>* Trans-catheter chemo-embolization (TACE) without rAd-p53 injection will be given every 21 days<br>* Other names: no other name;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | overall survival | tumor assessment will be performed every 6 weeks from starting study treatment to death or 2 years later | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety as assessed by adverse events, vital sign, lab tests, ECG and physical examination | safety variables: adverse events, vital sign, lab tests, ECG and physical examination | from the first study treatment to the 30 days after the last treatment (on an average of 6 months from the start treatment) | 
| progression-free survival | time to disease progression (death or progression), or censored | tumor assessment will be performed every 6 weeks from starting study treatment to disease progression or 2 years later |