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

Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01580202
• Other study ID #: AI463-246
• Status: Completed
• Phase: Phase 3
• First received: April 4, 2012
• Last updated: June 28, 2017
• Start date: April 2012
• Est. completion date: June 2017

Study information

• Verified date: June 2017
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Malignancy
• Neoplasms

Intervention

Drug:
• Entecavir
Entecavir 0.5mg daily per os
• Lamivudine
lamivudine 100mg daily per os

Locations

Country	Name	City	State
Korea, Republic of	Soon Chun Hyang University Bucheon Hospital	Bucheon-si
Korea, Republic of	National Cancer Center, Korea	Goyang	Gyeonggi
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Gyeonggi
Korea, Republic of	Seoul National University Boramae Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The cumulative probability of HBV reactivation	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	Incidence of HBV-related hepatitis flare	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
Secondary	Cumulative probability of emergence of genotypic resistance	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
Secondary	Incidence of hepatic decompensation and liver-related mortality		From the time of randomization until 24week after discontinuation of antiviral prophylaxis