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

Seoul National University

Status and phase: Completed; Phase 3

Conditions: Hepatitis B; Malignancy

Treatments: Drug: Lamivudine; Drug: Entecavir

Study type: Interventional

Funder types: Other

Identifiers

NCT01580202

AI463-246

Details and patient eligibility

About

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.

Full 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.

Enrollment: 180 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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180 participants in 2 patient groups

Lamivudine

Active Comparator group

Description:

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.

Treatment:

Drug: Lamivudine

Entecavir

Experimental group

Description:

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.

Treatment:

Drug: Entecavir