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

A Phase 4, Open-Label Study to Investigate the Efficacy and Safety of Tenofovir Disoproxil Fumarate (Viread(R)) in Preventing Hepatocellular Carcinoma Recurrence in Chronic Hepatitis B Virus Infected Patients With Low Viral Load at Baseline Treated With Radiofrequency Ablation or Resection

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.

Study Overview

• Status: Unknown
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Drug: Tenofovir disoproxil fumarate

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.

• Study Type: Interventional
• Enrollment (Anticipated): 124
• Phase: Phase 4

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PROMPT; Prompt therapy with Tenofovir disoproxil fumarate (Viread(R)) 300mg p.o	Drug: Tenofovir disoproxil fumarate; 300mg q.d. per oral; Other Names: Viread(R)
Other: 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)]	Drug: Tenofovir disoproxil fumarate; 300mg q.d. per oral; Other Names: Viread(R)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recurrence free survival	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		3 years
New onset ascites, variceal bleeding, hepatic encephalopathy		3 years
Child-Pugh score and MELD score at baseline and at final follow-up		3 years
Reactivation of hepatitis B	Increase in DNA 1log IU/mL at least 4 weeks apart	3 years

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Seung Woon Paik, M.D., Ph.D., Samsung Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): June 1, 2019

Study Registration Dates

• First Submitted: November 26, 2014
• First Submitted That Met QC Criteria: December 2, 2014
• First Posted (Estimate): December 4, 2014

Study Record Updates

• Last Update Posted (Estimate): December 4, 2014
• Last Update Submitted That Met QC Criteria: December 2, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Hepatocellular carcinoma, Recurrence
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Liver Neoplasms; Hepatitis; Carcinoma; Hepatitis B; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: 2014-09-149