TACE and Adefovir Compared With Transarterial Chemoembolization (TACE) Alone for Hepatitis B Virus (HBV)-Related Unresectable Hepatocellular Carcinoma (HCC)

Hepatocellular Carcinoma Clinical Trial

— TACE  

Official title:

Combination Therapy With TACE and Adefovir Compared With TACE Alone for HBV-related Unresectable Hepatocellular Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00960518
• Other study ID #: SHDSYY20090725
• Status: Recruiting
• Phase: Phase 2
• First received: August 14, 2009
• Last updated: August 14, 2009
• Start date: August 2009
• Est. completion date: August 2015

Study information

• Verified date: August 2009
• Source: Tongji University
• Contact: Daoyuan Wang, MD
• Phone: +86-21-6630058
• Email: ghealth2008[@]gmail.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in China, and approximately 90% of the patients with HCC are also infected with hepatitis B virus (HBV). For patients with unresectable disease, the goal of palliative treatment is to control symptoms and prolong survival. Transarterial chemoembolization (TACE) using iodized oil and chemotherapeutic agents combines the effect of targeted chemotherapy with that of ischemic necrosis induced by arterial embolization. It can be administered repeatedly and can prolong survival in patients with unresectable hypervascular HCC. The long-term prognosis, however, remains guarded because of frequent development of locoregional tumor recurrence, which, together with concomitant hepatic decompensation, is the main cause of death. Adefovir works by blocking reverse transcriptase, an enzyme that is crucial for the hepatitis B virus (HBV) to reproduce in the body. Based on these results, the investigators conducted a randomized controlled trial to test the hypothesis that adefovir treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after TACE treatment of HBV-related unresectable HCC.

Description:

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in China, and approximately 90% of the patients with HCC are also infected with hepatitis B virus (HBV). Until now, no standard therapy has been established for treatment of hepatocellular carcinoma. For patients with unresectable disease, the goal of palliative treatment is to control symptoms and prolong survival. Transarterial chemoembolization (TACE) using iodized oil and chemotherapeutic agents combines the effect of targeted chemotherapy with that of ischemic necrosis induced by arterial embolization. It can be administered repeatedly and can prolong survival in patients with unresectable hypervascular HCC. The long-term prognosis, however, remains guarded because of frequent development of locoregional tumor recurrence, which, together with concomitant hepatic decompensation, is the main cause of death. Recurrence in the liver remnant may originate from metastasis from the primary tumor or multicentric new primaries in a cirrhotic liver.

Adefovir works by blocking reverse transcriptase, an enzyme that is crucial for the hepatitis B virus (HBV) to reproduce in the body. It is approved for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (primarily ALT) or histologically active disease. The main benefit of adefovir over lamivudine (the first NRTI approved for the treatment of hepatitis B) is that it takes a much longer period of time before the virus develops resistance to it. Adefovir dipivoxil contains two pivaloyloxymethyl units, making it a prodrug form of Adefovir.

Based on these results, the investigators conducted a randomized controlled trial to test the hypothesis that adefovir treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after TACE treatment of HBV-related unresectable HCC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 216
• Est. completion date: August 2015
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

Inclusion Criteria:

• age:20-75 years old

• with a clinical diagnosis of primary liver cancer, with HBsAg positive,without any therapy for tumor

• single lesion with a diameter >6.5 cm,or multiple lesions locating within half liver or adjacent three lobe

• estimated liver remnant volume =40%

• with a liver function of Child-Pugh class A,and ALT=80IU/l.

Exclusion Criteria:

• reject to attend

• portal vein trunk has been compressed by tumor

• diffuse type cancer or with extensive cancer thrombus in main branches of PV,HV,IVC or bile duct

• with extrahepatic metastasis

• with obvious portal hypertension (with moderate to severe varix in esophagus and/or gastric fundus, enlarged spleen,WBC<4×109/L, PLT<80×109/L)

• with diabetes

• allergy to iodine

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatitis
• Hepatitis B
• Hepatitis B Virus
• Hepatocellular Carcinoma

Intervention

Drug:
• adefovir
adefovir at 10 mg daily for 48 weeks

Procedure:
• TACE
An emulsion that consisted of 50 mg of cisplatin and 10 mL of lipiodol at a volume ratio of 1:1 was injected into the blood supply artery of the tumor under fluoroscopic guidance. The injection could be slowed or discontinued if retrograde flow occurred. Embolization was subsequently performed with granules of gelatin sponge particles.

Locations

Country	Name	City	State
China	The Fourth Affiliated Hospital of Haerbin Medical University	Ha'er'bin	Heilongjiang
China	Shanghai 10th Hospital of Tongji University	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Tongji University	Interventional Radiology Research Group, Shanghai Radiology Society

Country where clinical trial is conducted

China, 

References & Publications (1)

Li M, Lu C, Cheng J, Zhang J, Cao C, Xu J, Xu J, Pan H, Zhong B, Tucker S, Wang D. Combination therapy with transarterial chemoembolization and interferon-alpha compared with transarterial chemoembolization alone for hepatitis B virus related unresectable hepatocellular carcinoma. J Gastroenterol Hepatol. 2009 Aug;24(8):1437-44. doi: 10.1111/j.1440-1746.2009.05863.x. Epub 2009 May 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the progression free survival (PFS)		3 months	Yes
Secondary	the rate of overall survival		1, 3, 5 years	Yes