Chemoembolization With or Without Antiviral Therapy for Unresectable HBV-related HCC With Low HBV DNA Replication

NCT ID: NCT01894269

Last Updated: 2013-07-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2016-07-31

Brief Summary

Although it is commonly accepted that antiviral therapy should be commenced before or during hepatocellular carcinoma (HCC) treatment if the patients have high viral loads and elevated ALT or total bilirubin values with signs of cirrhosis, the dilemma exists when HBV DNA and liver function (such as ALT, AST, TBIL) remains low level. Whether antiviral therapy make sense or not in these patients with no signs of hepatitis or high viral replication remains unclear, especially for the relatively advanced stage HCC patients receiving TACE. Thus, the investigators carried out this prospective control study to compare the survivals for patients after TACE between with or without antiviral therapy.

Detailed Description

In highly endemic areas, hepatitis B virus (HBV) infection plays a primary role in the etiology of HCC and is frequently observed in HCC patients. Patients with HBV-related HCC usually have a history of chronic HBV infection. Chemotherapy for other malignancies has been associated with HBV reactivation. Furthermore, in end stage liver disease due to HBV, levels of HBV replication have been correlated with liver function. For TACE, reports on HBV reactivation have been inconsistent. Some studies have demonstrated HBV reactivation, some have not , and others have shown decreased HBV DNA levels . The exact mechanism by which this occurs is still unknown. Although anti-HBV therapy has been reported to suppress HBV reactivation in various clinical settings with immunosuppressive conditions, few reports were concerned with the TACE treatment of HBV-related HCC. Also, the long-term effects of antiviral therapy in relatively advanced HCC patients after HCC remains unclear.

Although it is commonly accepted that antiviral therapy should be commenced before or during HCC treatment if the patients have high viral loads and elevated ALT or total bilirubin values with signs of cirrhosis, the dilemma exists when HBV DNA and liver function (such as ALT, AST, TBIL) remains low level. Therefore, we would call for the establishment of clinical practice guidelines on the antiviral therapy in HBV-related HCC patients, especially a consensus on the indications to administer nucleosides analogs (NAs).

Thus , the purpose of the investigators' study is to prospectively study the efficacy of nucleosides analogs (NAs) in transcatheter arterial chemoembolization for nonresectable hepatocellular carcinoma with relatively low HBV DNA replication and Child-Pugh grade A based on multivariate analysis of prognostic factors. The HBV DNA and liver function parameters will be monitored closely. Once the reactivation occurs in the control group, antiviral therapy would be administered immediately. The study had a interim analysis to allow the trial to be stopped if significant differences were detected. The accumulated data were examined when half patient was enrolled in the clinical trial.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Anti-viral treatment

Oral antiviral drugs will be commenced after TACE. That is: Lamivudine 100mg once daily; or Entecavir 0.5mg once daily.

Group Type: EXPERIMENTAL

Lamivudine 100mg once daily; or Entecavir 0.5mg once daily.

Intervention Type: DRUG

In experimental group, Lamivudine 100mg once daily; or Entecavir 0.5mg once daily will be commenced after TACE.

Control

No anti-viral therapy after TACE.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Lamivudine 100mg once daily; or Entecavir 0.5mg once daily.

In experimental group, Lamivudine 100mg once daily; or Entecavir 0.5mg once daily will be commenced after TACE.

Intervention Type: DRUG

Other Intervention Names

lamivudine 100 mg tablets (GlaxoSmithKline); Entecavir 0.5mg tablets (Bristol-Myers Squibb)

Eligibility Criteria

Inclusion Criteria

Male or female patients from 18 to 75 years of age with a diagnosis of HCC. A diagnosis of HCC based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL).

The patient has not been previously treated with surgery, radiation therapy, radiofrequency ablation, percutaneous ethanol or acetic acid injection, or cryoablation, or any other treatment with chemotherapeutic agents or sorafenib.

The patient has not been previously treated with any anti-viral agents, including interferon or nucleosides analogs (NAs).

Adults patients with a diagnosis of HCC which is not amenable to surgical resection ,local ablative therapy or any other radically cured treatment.

The MDT group of HCC agree to administer TACE in this patient.

Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria.

No serious concurrent medical illness.

Unresectable TNM stage Ⅲ or Ⅳ disease.

Zubrod-ECOG-WHO performance status: 0 or 1. and the estimated survival more than 4 months.

Not pregnant or breast-feeding patients

No significant renal impairment (creatinine clearance < 30 mL/minute) or patients on dialysis

No current infections requiring antibiotic therapy

Not on anticoagulation or suffering from a known bleeding disorder

No unstable coronary artery disease or recent MI

Ability to understand the protocol and to agree to and sign a written informed consent document

The following laboratory parameters at baseline:

Platelet count ≥ 70,000/µL

Hemoglobin ≥ 8.5 g/dL

Absolute neutrophil count (ANC) >1,500/mm3

Total bilirubin ≤ 1.5 mg/dL Serum albumin ≥ 35 g/L

Serum creatinine ≤ 1.5 x upper limit of normal

PT prolong time less than 3 seconds

Cirrhotic status of Child-Pugh class A only

ALT<2×upper limit of normal

Hepatitis B surface antigen positive

If hepatitis B e antigen positive, HBV DNA level <2000IU/mL; If hepatitis B e antigen negative, HBV-DNA<200IU/mL.

Exclusion Criteria

• History of HIV or HCV infection.

History of organ allograft

Known or suspected allergy to the investigational agents or any agent given in association with this trial.

Evidence of bleeding diathesis.

Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.

Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of study entry.

Serious non-healing wound, ulcer, or bone fracture

Known central nervous system tumors including metastatic brain disease

Any event > grade 2 National Cancer Institute [NCI]-Common Terminology Criteria for Adverse Events [CTCAE] version 3.0

Severe complication after TACE.

History of hepatotoxic medication within 8 wk prior to the current treatment.

History of corticosteroid administration.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Xiang-Ming Lao

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiao-Jun Lin, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Xiang-Ming Lao, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiang-Ming Lao, MD

Role: CONTACT

laoxming@mail.sysu.edu.cn

8620-87343114

Xiao-Jun Lin, MD

Role: CONTACT

linxj@sysucc.org.cn

8620-87343017

Facility Contacts

Xiang-Ming Lao, MD

Role: primary

laoxming@mail.sysu.edu.cn

8620-87343114

References

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Reference Type: BACKGROUND

PMID: 12124405 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 16608033 (View on PubMed)

Jang JW, Choi JY, Bae SH, Yoon SK, Chang UI, Kim CW, Cho SH, Han JY, Lee YS. A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization. Hepatology. 2006 Feb;43(2):233-40. doi: 10.1002/hep.21024.

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Lao XM, Wang D, Shi M, Liu G, Li S, Guo R, Yuan Y, Chen M, Li J, Zhang Y, Lin X. Changes in hepatitis B virus DNA levels and liver function after transcatheter arterial chemoembolization of hepatocellular carcinoma. Hepatol Res. 2011 Jun;41(6):553-63. doi: 10.1111/j.1872-034X.2011.00796.x. Epub 2011 Mar 29.

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Other Identifiers

sysucc-HCC010

Identifier Type: -

Identifier Source: org_study_id