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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Seoul National University Hospital
Sponsor:
Information provided by (Responsible Party):
Sook-Hyang Jeong, Seoul National University Bundang Hospital
ClinicalTrials.gov Identifier:
NCT01580202
First received: April 4, 2012
Last updated: December 15, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Malignancy
Hepatitis B
Drug: Entecavir
Drug: Lamivudine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • The cumulative probability of HBV reactivation [ Time Frame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis ] [ Designated as safety issue: No ]
    10-fold or more elevation in serum HBV DNA titers above nadir


Secondary Outcome Measures:
  • Incidence of HBV-related hepatitis flare [ Time Frame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis ] [ Designated as safety issue: No ]
    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

  • Cumulative probability of emergence of genotypic resistance [ Time Frame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis ] [ Designated as safety issue: No ]
    detection of mutations that have been shown in in vitro studies to confer resistance to either ETV or LAM

  • Incidence of hepatic decompensation and liver-related mortality [ Time Frame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis ] [ Designated as safety issue: No ]

Estimated Enrollment: 180
Study Start Date: April 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01580202

Contacts
Contact: Sook-Hyang Jeong, MD, PhD +82-31-787-7034 jsh@snubh.org

Locations
Korea, Republic of
National Cancer Center, Korea Recruiting
Goyang, Gyeonggi, Korea, Republic of, 410-769
Contact: Bo Hyun Kim, MD, PhD       bohkim@ncc.re.kr   
Principal Investigator: Bo Hyun Kim, MD, PhD         
Seoul National University Bundang Hospital Recruiting
Seongnam, Gyeonggi, Korea, Republic of, 463-707
Contact: Sook-Hyang Jeong       jsh@snubh.org   
Principal Investigator: Sook-Hyang Jeong, MD, PhD         
Seoul National University Boramae Hospital Recruiting
Seoul, Korea, Republic of, 156-707
Contact: Won Kim, MD, PhD       drwon1@snu.ac.kr   
Principal Investigator: Won Kim, MD, PhD         
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Jeong-Hoon Lee, MD, PhD       jhleemd@gmail.com   
Principal Investigator: Jeong-Hoon Lee, MD, PhD         
Sponsors and Collaborators
Seoul National University Hospital
Investigators
Principal Investigator: Sook-Hyang Jeong, MD, PhD Seoul National University Bundang Hospital
  More Information

No publications provided

Responsible Party: Sook-Hyang Jeong, Associate Professor, Seoul National University Bundang Hospital
ClinicalTrials.gov Identifier: NCT01580202     History of Changes
Other Study ID Numbers: AI463-246
Study First Received: April 4, 2012
Last Updated: December 15, 2013
Health Authority: Korea: Food and Drug Administration

Keywords provided by Seoul National University Hospital:
malignancy
hepatitis B
lamivudine
entecavir
prophylaxis

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Neoplasms
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Entecavir
Lamivudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014