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

Samsung Medical Center

Status and phase: Unknown; Phase 4

Conditions: Carcinoma, Hepatocellular

Treatments: Drug: Tenofovir disoproxil fumarate

Study type: Interventional

Funder types: Other

Identifiers

NCT02308319

2014-09-149

Details and patient eligibility

About

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.

Full 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.

Enrollment: 124 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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124 participants in 2 patient groups

PROMPT

Active Comparator group

Description:

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

Treatment:

Drug: Tenofovir disoproxil fumarate

Watchful monitoring

Other group

Description:

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

Treatment:

Drug: Tenofovir disoproxil fumarate