Clinical trial NCT01580202: Comparison of Prophylactic Antiviral Efficacy in Patients Undergoing Chemotherapy: Entecavir Versus Lamivudine
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malignancy
Hepatitis B
Keywords: malignancy
hepatitis B
lamivudine
entecavir
prophylaxis
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2012-04-18
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: The cumulative probability of HBV reactivation
timeFrame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis
Secondary outcomes:
measure: Incidence of HBV-related hepatitis flare
timeFrame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis
measure: Cumulative probability of emergence of genotypic resistance
timeFrame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis
measure: Incidence of hepatic decompensation and liver-related mortality
timeFrame: From the time of randomization until 24week after discontinuation of antiviral prophylaxis
Other outcomes:
Locations:
city: Goyang
country: Korea, Republic of
facility: National Cancer Center, Korea
state: Gyeonggi
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi
city: Bucheon-si
country: Korea, Republic of
facility: Soon Chun Hyang University Bucheon Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Boramae Hospital
Study officials:
affiliation: Seoul National University Bundang Hospital
name: Sook-Hyang Jeong, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: