Durvalumab for Advanced Hepatocellular Carcinoma in Patients With Active Chronic Hepatitis B Virus Infection

Phase 2

Active, not recruiting

• Conditions: Advanced Hepatocellular Carcinoma
• Interventions: Drug: Durvalumab

• Registration Number: NCT04294498
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

PD1 blockade has been approved as salvage therapy for advanced hepatocellular carcinoma (HCC). Although there is not solid evidence that PD1 blockade would induce hepatitis B virus (HBV) reactivation, previous clinical trials of PD1 blockade required enrolled patients to receive anti-HBV medications and control the viral load to be under 100-2000 IU/mL before initiation of PD1 blockade therapy. Such a requirement may not be necessary and could delay the treatment. Guidelines for prevention of chemotherapy induced HBV reactivation only suggest combining anti-HBV medications during the chemotherapy course without such a requirement of very load HBV viral load.

The investigators hypothesized that under anti-HBV medications, patients with advanced HCC and active chronic hepatitis B virus (HBV) infection can receive durvalumab treatment without increased risks of HBV reactivation and related complications.

Detailed Description

Although durvalumab has not been approved as treatment for HCC, similar PD1 blockade agents such as nivolumab and pembrolizumab have gain approval as salvage therapy for advanced HCC. The investigators will enroll 43 patients with active (defined as serum viral load \> 2000 IU/mL) chronic HBV infection (defined as positive serum HBV surface antigen). All patients would receive entecavir within 7 days of initiation of durvalumab treatment. Durvalumab 1500 mg would be given intravenously every 4 weeks until confirmed disease progression, intolerable side effects, or completion of 24 treatment. Tumor assessment will be performed every 8-12 weeks. HBV viral load will be monitored at least once per month. Entecavir treatment will be continued at least 6 months after discontinuation of durvalumab treatment.

Study Timeline

• Study First Submitted: 2020-02-25
• Study First Submitted QC: 2020-03-01
• Study First Posted: 2020-03-04
• Study Start: 2020-11-02
• Primary Completion: 2024-09-01
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-21
• Last Update Posted: 2025-03-26
• Study Completion: 2026-09-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Durvalumab	Durvalumab	Durvalumab

Primary Outcome Measures

Name	Time	Method
The rate of HBV reactivation during durvalumab treatment	30 months	To assess the rate of HBV reactivation during durvalumab treatment, defined as a ≥2 log (100-fold) increase in serum HBV DNA compared to the baseline level.

Secondary Outcome Measures

Name	Time	Method
The rate of hepatitis flare during durvalumab treatment	30 months	To assess the rate of hepatitis flare, defined as an ALT increase to ≥3 times the baseline level and \>100 U/L, during durvalumab treatment.
To assess the efficacy of durvalumab treatment	30 months	To assess the efficacy of durvalumab treatment, as determined by overall survival.
To assess the rate of HBV-associated hepatitis during durvalumab treatment.	30 months	To assess the rate of HBV-associated hepatitis, defined as HBV reactivation plus hepatitis flare, during durvalumab treatment.
To assess the adverse events during durvalumab treatment.	30 months	To assess the adverse events, defined by CTC-AE version 5.0, during durvalumab treatment.

Trial Locations

Locations (1)

National Taiwan University Hospital; 🇨🇳 Taipei City, Taiwan