Prompt Or Watchful Monitoring for Hepatitis B Virus Related Hepatocellular Carcinoma Without Elevated viRal Load

NCT ID: NCT02308319

Last Updated: 2014-12-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2019-06-30

Brief Summary

Antiviral therapy for HBV may play an important role here, as a large observation study from Taiwan reported that the use of nucleos(t)ide analogues (NUC) was associated with 33% reduction in HCC recurrence. In the first randomized controlled trial evaluating the use of NUC after surgical resection for HCC, NUC therapy was associated with better 2-year overall (94% vs. 62%) and recurrence-free (56% vs. 20%) survival. However, patients with active liver disease should be treated regardless of their impact on HCC recurrence (patients with high serum HBV DNA and abnormal ALT). What is less clear is that whether patients with low level HBV DNA, and normal serum ALT levels should be treated to reduce HCC recurrence.

In this trial, we will investigate to determine the efficacy of the treatment with Tenofovir disoproxil fumarate (Viread(R)) as measured by the cumulative incidence rate of hepatocellular carcinoma (HCC) at 3 year after curative treatment with radiofrequency ablation (RFA) or surgical resection (SR) in chronic hepatitis B virus (HBV) infected patients with low viral load.

Detailed Description

HCC is a major global health problem, which is the third leading cause of cancer-related deaths, and accounts for 7% of all cancers worldwide. Curative treatment, such as SR, RFA has improved patients prognosis, however, even after successful curative treatment, high rates of disease recurrence limiting overall survival in HCC patients. In this regard, method to reduce HCC recurrence is an essential component of a therapeutic strategy to maximize outcome.

Antiviral therapy for HBV may play an important role here, as a large observation study from Taiwan reported that the use of NUCs was associated with 33% reduction in HCC recurrence. In the first randomized controlled trial evaluating the use of NUC after surgical resection for HCC, NUC therapy was associated with better 2-year overall (94% vs. 62%) and recurrence-free (56% vs. 20%) survival. However, patients with active liver disease should be treated regardless of their impact on HCC recurrence (patients with high serum HBV DNA and abnormal ALT). What is less clear is that whether patients with low level HBV DNA, and normal serum ALT levels should be treated to reduce HCC recurrence.

In the randomized controlled trial by Yin et al, antiviral therapy was also beneficial in Chronic hepatitis B patients with low viral load (HBV DNA < 104 copies/ml). However, there is a need for further validation of their finding for several reasons. First, the baseline characteristics between two groups were not same (more advanced tumors in the control arm). Second, the recurrence rates in the control arm was too high (about 80%), and the number of patients was small (control = 32, antiviral therapy = 22). Third, HBV DNA levels at 6 months was decreased in the antiviral therapy group (3.36 ± 0.68 log10 copies/ml vs. 4.66 ± 1.38 log10 copies/ml), but was not optimal. The used drugs were lamivudine, adefovir plus lamivudine or entecavir 0.5 mg. With more potent antiviral drug, better outcome is expected.

In this trial, we will investigate to determine the efficacy of the treatment with Tenofovir disoproxil fumarate (Viread(R)) as measured by the cumulative incidence rate of hepatocellular carcinoma (HCC) at 3 year after curative treatment with radiofrequency ablation (RFA) or surgical resection (SR) in chronic hepatitis B virus (HBV) infected patients with low viral load.

Conditions

Carcinoma, Hepatocellular

Study Design

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

Study Groups

PROMPT

Prompt therapy with Tenofovir disoproxil fumarate (Viread(R)) 300mg p.o

Group Type: ACTIVE_COMPARATOR

Tenofovir disoproxil fumarate

Intervention Type: DRUG

300mg q.d. per oral

Watchful monitoring

Wait and treat with Tenofovir disoproxil fumarate (Viread(R)) when active liver disease is present \[defined as HBV DNA \>2,000 IU/ml and abnormal ALT (\>40 IU/ml)\]

Group Type: OTHER

Tenofovir disoproxil fumarate

Intervention Type: DRUG

300mg q.d. per oral

Interventions

Tenofovir disoproxil fumarate

300mg q.d. per oral

Intervention Type: DRUG

Other Intervention Names

Viread(R)

Eligibility Criteria

Inclusion Criteria

• Hepatocellular carcinoma (clinically or histologically)
• chronic hepatitis B
• serum HBV DNA < 2000 IU/mL
• HCC stage BCLC 0 or A
• treated or will be treated with RFA or surgical resection

Exclusion Criteria

• co-infected with HCV, HIV
• currently using antiviral drug (lamivudine, adefovir, clevudine, tenofovir, entecavir, telbivudine) or interferon
• other malignancy
• dialysis
• pregnancy

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

Sponsors

Samsung Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Seung Woon Paik, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Samsung Medical Center

Central Contacts

Seung Woon Paik, M.D., Ph.D.

Role: CONTACT

sw.paik@samsung.com

82-2-3410-3409

Dong Hyun Sinn, M.D., Ph.D.

Role: CONTACT

dh.sinn@samsung.com

82-2-3410-3012

Other Identifiers

2014-09-149

Identifier Type: -

Identifier Source: org_study_id