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

This study is currently recruiting participants.
Verified August 2009 by Tongji University
Sponsor:
Collaborator:
Interventional Radiology Research Group, Shanghai Radiology Society
Information provided by:
Tongji University
ClinicalTrials.gov Identifier:
NCT00960518
First received: August 14, 2009
Last updated: NA
Last verified: August 2009
History: No changes posted

August 14, 2009
August 14, 2009
August 2009
August 2012   (final data collection date for primary outcome measure)
the progression free survival (PFS) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
Same as current
No Changes Posted
the rate of overall survival [ Time Frame: 1, 3, 5 years ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
TACE and Adefovir Compared With Transarterial Chemoembolization (TACE) Alone for Hepatitis B Virus (HBV)-Related Unresectable Hepatocellular Carcinoma (HCC)
Combination Therapy With TACE and Adefovir Compared With TACE Alone for HBV-related Unresectable Hepatocellular Carcinoma

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hepatitis B Virus
  • Hepatocellular Carcinoma
  • 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.
  • Placebo Comparator: 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.
    Intervention: Procedure: TACE
  • Experimental: TACE+adefovir
    patients received adefovir, at a dose of 10 mg daily after TACE treatment, for 48 weeks
    Intervention: Drug: adefovir
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 May 21; [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
216
August 2015
August 2012   (final data collection date for primary outcome measure)

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
Both
20 Years to 75 Years
No
Contact: Daoyuan Wang, MD +86-21-6630058 ghealth2008@gmail.com
China
 
NCT00960518
SHDSYY20090725
Yes
Shanghai 10th Hospital, Tongji University
Tongji University
Interventional Radiology Research Group, Shanghai Radiology Society
Study Chair: Maoquan Li, MD, PhD Interventional Radiology Research Group, Shanghai Radiology Society
Tongji University
August 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP