Comparison of Prophylactic Antiviral Efficacy in Patients Undergoing Chemotherapy: Entecavir Versus Lamivudine

June 28, 2017 updated by: Sook-Hyang Jeong, Seoul National University Hospital

A Randomized, Open Labeled, Multicenter Study Comparing Entecavir Versus Lamivudine as Antiviral Prophylaxis for Patients With Hepatitis B Infection Undergoing Cytotoxic Chemotherapy for Malignant Tumors

Patients with chronic hepatitis B who are undergoing anticancer chemotherapy are at risk of HBV reactivation and hepatitis flare. Lamivudine (LAM) prophylaxis has been recommended in such circumstance according to the practice guidelines despite of limited evidence. However, failure of LAM prophylaxis including virologic breakthrough and withdrawal hepatitis occurs occasionally, which may lead to liver-related morbidity and mortality as well as premature interruption or a delay of chemotherapy. Given relatively frequent drug resistance of LAM, studies on the proper prophylactic antiviral regimen is warranted. The present multicenter, prospective, randomized study aims to compare the effect of entecavir (ETV) versus LAM for the prevention of HBV reactivation in HBsAg-positive patients with hematologic and oncologic malignancy undergoing cytotoxic chemotherapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Chronic hepatitis B virus (HBV) carriers who are undergoing anticancer chemotherapy are at risk of HBV reactivation and hepatitis flare, and lamivudine (LAM) prophylaxis is recommended according to the practice guidelines despite of limited evidence. However, failure of LAM prophylaxis defined as virologic breakthrough during LAM therapy and withdrawal hepatitis after discontinuation of LAM therapy occurs occasionally, which may lead to liver-related morbidity and mortality as well as premature interruption or a delay of chemotherapy. Considering that LAM therapy showed relatively higher rates of drug resistance and of withdrawal hepatitis, studies on the better choice of prophylactic antiviral regimen is warranted.

The purpose of our study is to conduct a multicenter, prospective, randomized study comparing the effect of entecavir (ETV) versus LAM for the prevention of HBV reactivation in HBsAg-positive patients with hematologic and oncologic malignancy undergoing cytotoxic chemotherapy.

A total one hundred eighty HBV carriers with malignancy undergoing chemotherapy will be randomly assigned to each prophylactic therapy arm of ETV and LAM group. The primary endpoint of the study is the HBV reactivation rate during antiviral therapy and 6 months after discontinuation of prophylactic antiviral therapy.

If the prophylactic efficacy of ETV is superior to that of LAM, ETV will be the preferred prophylactic therapy for HBsAg-positive cancer patients undergoing chemotherapy.

Study Type

Interventional

Enrollment (Actual)

180

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Bucheon-si, Korea, Republic of, 14584
        • Soon Chun Hyang University Bucheon Hospital
      • Seoul, Korea, Republic of, 110-744
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 156-707
        • Seoul National University Boramae Hospital
    • Gyeonggi
      • Goyang, Gyeonggi, Korea, Republic of, 410-769
        • National Cancer Center, Korea
      • Seongnam, Gyeonggi, Korea, Republic of, 463-707
        • Seoul National University Bundang Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • 18 years or older
  • positive for HBsAg for at least 6 months
  • inactive or active carrier of HBV with ALT level <2xULN, chronic hepatitis and compensated cirrhosis (Child-Pugh class A)
  • malignant tumors: non-Hodgkin's lymphoma undergoing systemic chemotherapy; solid tumors undergoing chemotherapy (including adjuvant/neoadjuvant chemotherapy or concurrent chemoradiation therapy)

Exclusion Criteria:

  • positive for anti-HCV or anti-HIV antibodies
  • decompensated cirrhosis or hepatocellular carcinoma
  • expected survival of less than 1 year

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Lamivudine
LAM (100 mg/day) will be started within 1 week prior to initiation of the 1st cycle of chemotherapy, and continued until 24 weeks after completion of the last chemotherapy.
Drug: Lamivudine
lamivudine 100mg daily per os
Experimental: Entecavir
ETV (0.5 mg/day) will be started within 1 week prior to initiation of the 1st cycle of chemotherapy, and continued until 24 weeks after completion of the last chemotherapy.
Drug: Entecavir
Entecavir 0.5mg daily per os

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The cumulative probability of HBV reactivation
Time Frame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis
10-fold or more elevation in serum HBV DNA titers above nadir
From the time of randomization until 24week after discontinuation of antiviral prophylaxis

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of HBV-related hepatitis flare
Time Frame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis
greater than 3-fold increase of ULN (upper limit of a normal reference value) of a serum ALT level that exceeded 100 IU/L during antiviral prophylaxis and 24 week after discontinuation of antiviral prophylaxis
From the time of randomization until 24week after discontinuation of antiviral prophylaxis
Cumulative probability of emergence of genotypic resistance
Time Frame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis
detection of mutations that have been shown in in vitro studies to confer resistance to either ETV or LAM
From the time of randomization until 24week after discontinuation of antiviral prophylaxis
Incidence of hepatic decompensation and liver-related mortality
Time Frame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis
From the time of randomization until 24week after discontinuation of antiviral prophylaxis

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seoul National University Hospital

Investigators

  • Principal Investigator: Sook-Hyang Jeong, MD, PhD, Seoul National University Bundang Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2012

Primary Completion (Actual)

June 1, 2017

Study Completion (Actual)

June 1, 2017

Study Registration Dates

First Submitted

April 4, 2012

First Submitted That Met QC Criteria

April 17, 2012

First Posted (Estimate)

April 18, 2012

Study Record Updates

Last Update Posted (Actual)

June 29, 2017

Last Update Submitted That Met QC Criteria

June 28, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AI463-246

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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