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. (see Contacts and Locations)
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
  Purpose

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.


Condition Intervention Phase
Hepatitis B Virus
Hepatocellular Carcinoma
Drug: adefovir
Procedure: TACE
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Combination Therapy With TACE and Adefovir Compared With TACE Alone for HBV-related Unresectable Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by Tongji University:

Primary Outcome Measures:
  • the progression free survival (PFS) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • the rate of overall survival [ Time Frame: 1, 3, 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 216
Study Start Date: August 2009
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Experimental: TACE+adefovir
patients received adefovir, at a dose of 10 mg daily after TACE treatment, for 48 weeks
Drug: adefovir
adefovir at 10 mg daily for 48 weeks

Detailed 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.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00960518

Contacts
Contact: Daoyuan Wang, MD +86-21-6630058 ghealth2008@gmail.com

Locations
China, Heilongjiang
The Fourth Affiliated Hospital of Haerbin Medical University Recruiting
Ha'er'bin, Heilongjiang, China, 150001
Contact: Baozhong Shen, MD    +86-451-82576888    drbaozhong.shen@gmail.com   
Principal Investigator: Baozhong Shen, MD         
China, Shanghai
Shanghai 10th Hospital of Tongji University Recruiting
Shanghai, Shanghai, China, 200025
Contact: Maoquan Li, MD, PhD    +86-21-6630058    drmaoquan.li@gmail.com   
Principal Investigator: Maoquan Li, MD, PhD         
Sponsors and Collaborators
Tongji University
Interventional Radiology Research Group, Shanghai Radiology Society
Investigators
Study Chair: Maoquan Li, MD, PhD Interventional Radiology Research Group, Shanghai Radiology Society
  More Information

Publications:
Responsible Party: Shanghai 10th Hospital, Tongji University
ClinicalTrials.gov Identifier: NCT00960518     History of Changes
Other Study ID Numbers: SHDSYY20090725
Study First Received: August 14, 2009
Last Updated: August 14, 2009
Health Authority: China: Food and Drug Administration

Keywords provided by Tongji University:
HBV-related unresectable HCC
TACE
adefovir
recurrence rate

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Carcinoma, Hepatocellular
Carcinoma
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Adefovir
Adefovir dipivoxil
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014