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

This study is currently recruiting participants.
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

April 4, 2012
December 15, 2013
April 2012
June 2014   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01580202 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Comparison of Prophylactic Antiviral Efficacy in Patients Undergoing Chemotherapy: Entecavir Versus Lamivudine
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Malignancy
  • Hepatitis B
  • Drug: Entecavir
    Entecavir 0.5mg daily per os
  • Drug: Lamivudine
    lamivudine 100mg daily per os
  • 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.
    Intervention: Drug: Lamivudine
  • 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.
    Intervention: Drug: Entecavir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
180
December 2014
June 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Sook-Hyang Jeong, MD, PhD +82-31-787-7034 jsh@snubh.org
Korea, Republic of
 
NCT01580202
AI463-246
Yes
Sook-Hyang Jeong, Seoul National University Bundang Hospital
Seoul National University Hospital
Not Provided
Principal Investigator: Sook-Hyang Jeong, MD, PhD Seoul National University Bundang Hospital
Seoul National University Hospital
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP