Atezolizumab Plus Bevacizumab With HCC and HBV Infection

Carcinoma, Hepatocellular Clinical Trial

Official title: Atezolizumab Plus Bevacizumab for Patients With Advanced Hepatocellular Carcinoma (HCC) and Chronic Hepatitis B Virus (HBV) Infection

Status Recruiting

Clinical Trial Summary

This is a single-arm clinical trial. The main objective is to determine the efficacy of atezolizumab+bevacizumab therapy in patients with advanced hepatocellular carcinoma and with chronic hepatitis B virus infection. All eligible patients will receive atezolizumab + bevacizumab therapy.

Clinical Trial Description

Combination of atezolizumab, an immune checkpoint inhibitors (ICI), and bevacizumab, an anti-angiogenic antibody, has shown promising anti-tumor activity and good safety profile in patients with advanced hepatocellular carcinoma (HCC) and good liver function reserves (Child-Pugh class A). Currently all trials of ICI-based therapy for HCC enrolled only patients with very low HBV viral loads if they had chronic HBV infection because of the concern of the risk of HBV reactivation on the severity and management of liver-related adverse events, particularly immune-related hepatitis.

The investigators hypothesize that in patients with advanced HCC, chronic HBV infection, and adequate liver function reserves, the safety profile of ICI-based therapy should be similar to those in other patient populations as long as prophylactic anti-HBV treatment is given, regardless the baseline HBV viral load. This is because in patients with patients with lymphoma and chronic HBV infection, who have the highest risk of HBV reactivation after cytotoxic or immunosuppressive therapy, no HBV-related complications of clinical significance were noted as long as prophylactic anti-HBV treatment started before the administration of cytotoxic or immunosuppressive therapy.

This is a single-arm clinical trial. Key eligibility criteria will include the following:

histologically proven, locally advanced or metastatic and/or unresectable HCC that is not amenable to curative surgical and/or locoregional therapies; no prior systemic therapy for HCC; documented chronic HBV infection with HBV DNA > 2000 IU/mL obtained within 28 days prior to initiation of study treatment; at least one measurable (per RECIST 1.1) lesion; ECOG Performance Status of 0 or 1; and Child-Pugh class A.

All eligible patients will receive atezolizumab 1200 mg IV plus bevacizumab 15 mg/kg IV on day 1 every 3 weeks. Study treatment will continue until documented tumor progression or occurrence of unacceptable toxicity. All eligible subjects will receive anti-HBV treatment (per local standard of care; e.g., entecavir) prior to start of study treatment and continue anti-HBV treatment for the length of the study. The primary endpoint is overall response rate defined as a complete or partial response, as determined by the investigator according to RECIST v1.1. The secondary endpoints will include safety measures (e.g., the proportion of subjects with ≥ grade 3 liver-related adverse events (AE) (according to NCI CTCAE v5.0), incidence and severity of all adverse events/ immune-related adverse events, incidence of HBV reactivation/ HBV-related hepatitis flare) and efficacy measures (e.g., objective response rate, progression-free survival, duration of response, and overall survival). This study plan to enroll 48 evaluable subjects, defined as subjects who receive 3 cycles of study treatment and the first image evaluation for tumor response. The estimated time of enrollment will be 2 years. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

• NCT number: NCT04180072
• Study type: Interventional
• Source: National Health Research Institutes, Taiwan
• Contact: Ya-Ling Wu, BS
• Phone: 886-3-7206166
• Email: yalin@nhri.edu.tw
• Status: Recruiting
• Phase: N/A
• Start date: March 12, 2020
• Completion date: December 31, 2025