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

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

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.

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)

Inclusion Criteria:

1. histopathologically diagnosed HCC;
2. unresectable;
3. over 18 years old;
4. with an Eastern Cooperative Oncology Group (ECOG) score of 0-2;
5. with Barcelona Clinic Liver Cancer (BCLC) Stage of B or C;
6. with Child-Pugh score A or B;
7. with normal tests of hemogram, blood coagulation, liver and kidney function; 8. signed the informed consent form.

Exclusion Criteria:

1. Serious blood coagulation disorder, bleeding tendency, platelet < 6 * 1000000000/L;
2. have serious heart, lung function abnormalities or severe diabetes patients;
3. active infection;
4. liver function Child-Pugh grade C;
5. secondary and diffuse hepatocellular carcinoma patients;
6. extensive metastasis;
7. severe atherosclerosis;
8. AIDS patients;
9. serious thrombotic or embolic events within 6 months;
10. renal insufficiency requiring hemodialysis or peritoneal dialysis;

12. pregnant or lactating women;

13. mental disorder or disease.