A Study Evaluating Atezolizumab, With or Without Bevacizumab, in Patients With Unresectable Hepatocellular Carcinoma and Child-Pugh B7 and B8 Cirrhosis

Hepatocellular Carcinoma Clinical Trial

— Kirros  

Official title:

A Phase II, Open-Label, Multi-Cohort, Multicenter Study in Patients With Unresectable Hepatocellular Carcinoma and Child-Pugh B7 and B8 Cirrhosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06096779
• Other study ID #: ML44719
• Status: Recruiting
• Phase: Phase 2
• Start date: May 31, 2024
• Est. completion date: November 16, 2026

Study information

• Verified date: May 2024
• Source: Genentech, Inc.
• Contact: Reference Study ID Number: ML44719 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and efficacy of atezolizumab and bevacizumab, or atezolizumab alone, as first-line treatment in participants with unresectable, locally advanced or metastatic hepatocellular carcinoma (HCC) with Child-Pugh B7 or B8 cirrhosis.

Description:

This is a Phase II, open-label, multicohort, multicenter study in participants with unresectable, locally advanced, or metastatic hepatocellular carcinoma (HCC) who have Child-Pugh B7 or B8 liver cirrhosis and have received no prior systemic therapy in this treatment setting. The study is designed to non-comparatively evaluate the safety and efficacy of atezolizumab plus bevacizumab (Cohort A) or atezolizumab monotherapy (Cohort B) in this population.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: November 16, 2026
• Est. primary completion date: May 2, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

General Inclusion Criteria:

• Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients
• Disease that is not amenable to curative surgical and/or locoregional therapies
• No prior systemic treatment (including systemic investigational agents) for locally advanced or metastatic and/or unresectable HCC
• Measurable disease (at least one untreated target lesion) according to RECIST v1.1
• ECOG Performance Status of 0-2 within 7 days prior to initiation of study treatment
• Child-Pugh B7 or B8 cirrhosis at screening and within 7 days prior to study treatment
• Adequate hematologic and end-organ function
• Life expectancy of at least 12 weeks
• Female participants of childbearing potential must be willing to avoid pregnancy and egg donation

General Exclusion Criteria:

• Pregnancy or breastfeeding
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Treatment with locoregional therapy to liver within 28 days prior to initiation of study treatment, or non-recovery from side effects of any such procedure
• Treatment with systemic immunostimulatory agents
• Treatment with systemic immunosuppressive medication
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment
• Inadequately controlled hypertension
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• History of malignancy other than HCC within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
• Known fibrolamellar HCC, sarcomatoid HCC, other rare HCC variant, or mixed cholangiocarcinoma and HCC
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• Prior allogeneic stem cell or solid organ transplantation
• Listed for liver transplantation
• Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV)
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding
• A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
• Grade =3 hemorrhage or bleeding event within 6 months prior to initiation of study treatment
• History of hepatic encephalopathy requiring hospitalization or treatment escalation within 6 months prior to study treatment, or any continued symptoms of encephalopathy despite medical management
• History, planned, or recommended placement of transjugular intrahepatic portosystemic shunt (TIPS)
• History of ascites requiring therapeutic paracentesis over the last 3 months
• History of spontaneous bacterial peritonitis within last 12 months

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Fibrosis
• Hepatocellular Carcinoma

Intervention

Drug:
• Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1 of each 21-day cycle.
• Bevacizumab
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
Puerto Rico	Pan American Center for Oncology Trials, LLC	Rio Piedras
United States	LSU Health Baton Rouge; North Clinic	Baton Rouge	Louisiana
United States	Our Lady of the Lake Physician Group	Baton Rouge	Louisiana
United States	Montefiore Medical Center	Bronx	New York
United States	Liver Institute at Methodist Dallas	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Maine
United States	The West Clinic (East Campus)	Germantown	Tennessee
United States	Kaiser Permanente Westside Medical Center	Hillsboro	Oregon
United States	Kelsey Research Foundation	Houston	Texas
United States	University of Southern California-Keck School of Medicine -1975 Zonal Ave	Los Angeles	California
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Rutgers Cancer Institute of New Jersey at University Hospital	Newark	New Jersey
United States	University of Southern California; Oncology/Hematology	Newport Beach	California
United States	University of California Irvine Medical Center	Orange	California
United States	Veterans Affairs Pittsburgh Healthcare System - NAVREF - PPDS	Pittsburgh	Pennsylvania
United States	University of California Davis Medical Center	Sacramento	California
United States	Benaroya Research Institute at Virginia Mason	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Adverse Events		Baseline through the end of the study (up to approximately 36 months)
Secondary	Objective Response Rate (ORR)	Investigator-assessed confirmed ORR is defined as proportion of participants with a CR/PR on two consecutive occasions = 4 weeks apart with the use of RECIST v1.1 and HCC mRECIST in Cohorts A and B.	Randomization up to approximately 36 months
Secondary	Duration of Response (DOR)	Investigator-assessed DOR is defined as the time from the first occurrence of a confirmed objective response to the time of disease progression, or death from any cause, whichever occurs first, with the use of RECIST v1.1 and HCC mRECIST in Cohorts A and B	Randomization up to approximately 36 months
Secondary	Progression Free Survival (PFS)	Investigator-assessed PFS is defined as the time from treatment initiation to the first occurrence of disease progression with the use of RECIST v1.1 and HCC mRECIST, or death from any cause, whichever occurs first, in Cohorts A and B.	Randomization up to approximately 36 months
Secondary	Overall Survival (OS)	OS is defined as the time from treatment initiation to the date of death due to any cause in Cohorts A and B.	Randomization up to approximately 36 months
Secondary	Change From Baseline in EORTC QLQ-C30 Scores	The QLQ-C30 is a validated, reliable self-reported measure. It consists of 30 questions that assess five aspects of participant functioning, three symptom scales, global health status and quality of life (QoL), and six single items with a recall period of the previous week. Scale scores can be obtained for the multi-item scales. The functioning and symptoms items are scored on a 4-point scale that ranges from "not at all" to "very much," and the global health status and QoL items are scored on a 7-point scale that ranges from "very poor" to "excellent."	Baseline up to approximately 36 months
Secondary	Change From Baseline in QLQ-HCC18 Scores	The EORTC QLQ-HCC18 is a disease-specific measure designed for use along with the EORTC QLQ-C30 in patients with HCC. It contains six multi-item symptom scales, and two single-item scales for a total of 18 questions with a recall period the past week.	Baseline up to approximately 36 months
Secondary	Change from baseline in PRO-CTCAE Scores	The PRO-CTCAE is a validated item bank that is used to characterize the presence, frequency of occurrence, severity, and/or degree of interference with daily function of 78 patient-reportable symptomatic treatment toxicities.	Baseline up to approximately 36 months
Secondary	Change From Baseline in IL46 Scores	The EORTC IL46 is a single question that assesses bother (burden) of treatment. It is rated on a scale from 1 to 4, ranging from "not at all" to "very much".	Baseline up to approximately 36 months