A Study Evaluating Atezolizumab, With or Without Bevacizumab, in Patients With Unresectable Hepatocellular Carcinoma and Child-Pugh B7 and B8 Cirrhosis
- Registration Number
- NCT06096779
- Lead Sponsor
- Genentech, Inc.
- Brief 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.
- Detailed 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 & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
- 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
- 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
- Patients who have a known concurrent malignancy that is progressing or requires active treatment, who have not completely recovered from treatment, or who have a significant malignancy history that, in the opinion of the investigator, should preclude participation.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: Atezolizumab+Bevacizumab Bevacizumab Participants will receive Atezolizumab plus Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Cohort A: Atezolizumab+Bevacizumab Atezolizumab Participants will receive Atezolizumab plus Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Cohort B: Atezolizumab Atezolizumab Participants will receive Atezolizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Adverse Events Baseline through the end of the study (up to approximately 36 months) An adverse event is any untoward medical occurrence in a patient or clinical study participant temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Severity is determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) in Cohort A and B
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) Baseline up to approximately 36 months 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.
Duration of Response (DOR) Baseline up to approximately 36 months 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
Overall Survival (OS) Baseline up to approximately 36 months OS is defined as the time from treatment initiation to the date of death due to any cause in Cohorts A and B.
Change From Baseline in EORTC QLQ-C30 Scores Baseline up to approximately 36 months The European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC 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."
Percentage of Patient-Reported Overall Adverse Event Burden Baseline up to approximately 36 months 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".
Objective Response Rate (ORR) Baseline up to approximately 36 months Investigator-assessed confirmed ORR is defined as proportion of participants with a complete response/partial response (CR/PR) on two consecutive occasions ≥ 4 weeks apart with the use of Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) and hepatocellular carcinoma (HCC) modified Response Evaluation Criteria in Solid Tumors (mRECIST) in Cohorts A and B.
Change From Baseline in EORTC QLQ-HCC18 Scores Baseline up to approximately 36 months 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.
Change from baseline in PRO-CTCAE Scores Baseline up to approximately 36 months The Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (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.
Trial Locations
- Locations (60)
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
University of Southern California-Keck School of Medicine -1975 Zonal Ave
🇺🇸Los Angeles, California, United States
University of Southern California
🇺🇸Newport Beach, California, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
California Liver Research Institute
🇺🇸Pasadena, California, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
Stanford Health Care
🇺🇸Stanford, California, United States
Harbor UCLA Medical Center
🇺🇸Torrance, California, United States
Cedars Sinai Comprehensive Transplant Center
🇺🇸West Hollywood, California, United States
Rocky Mountain Cancer Centers (Williams) - USOR
🇺🇸Denver, Colorado, United States
Hartford Healthcare Cancer Institute at Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Washington DC VA Medical Center
🇺🇸Washington, District of Columbia, United States
Orlando Health Inc.
🇺🇸Orlando, Florida, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Illinois Health Outpatient Care Center
🇺🇸Chicago, Illinois, United States
The Duchossois Center for Advanced Medicine
🇺🇸Chicago, Illinois, United States
University of Kentucky - Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
LSU Health Baton Rouge
🇺🇸Baton Rouge, Louisiana, United States
Our Lady of the Lake Physician Group
🇺🇸Baton Rouge, Louisiana, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Veterans Affairs Ann Arbor Healthcare System
🇺🇸Ann Arbor, Michigan, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Saint Luke?s Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
MorristownMedicalCenter
🇺🇸Morristown, New Jersey, 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
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
James J Peters Veterans Administration Medical Center - NAVREF
🇺🇸Bronx, New York, United States
Long Island Heart Associates
🇺🇸Mineola, New York, United States
R.J. Zuckerberg Cancer Hospital/Northwell Health - BRANY - PPDS
🇺🇸New Hyde Park, New York, United States
NYU Langone Medical Center
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Dayton VA Medical Center - NAVREF - PPDS
🇺🇸Dayton, Ohio, United States
The University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Kaiser Permanente Westside Medical Center
🇺🇸Hillsboro, Oregon, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Veterans Affairs Pittsburgh Healthcare System - NAVREF - PPDS
🇺🇸Pittsburgh, Pennsylvania, United States
The West Clinic (East Campus)
🇺🇸Germantown, Tennessee, United States
Nashville General Hospital at Meharry
🇺🇸Nashville, Tennessee, United States
Liver Institute at Methodist Dallas
🇺🇸Dallas, Texas, United States
Moody Outpatient Center ? Parkland Health
🇺🇸Dallas, Texas, United States
Texas Oncology (Worth) - USOR
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Texas Oncology - Denison Cancer Center
🇺🇸Denison, Texas, United States
Kelsey Research Foundation
🇺🇸Houston, Texas, United States
Michael E Debakey VA Medical Center - NAVREF - PPDS
🇺🇸Houston, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Intermountain Healthcare
🇺🇸Murray, Utah, United States
Intermountain Cancer Center
🇺🇸Saint George, Utah, United States
Inova Schar Cancer Institute
🇺🇸Falls Church, Virginia, United States
Maryview Hospital, Inc.
🇺🇸Newport News, Virginia, United States
Bon Secours St. Mary's Hospital
🇺🇸Richmond, Virginia, United States
VCU Medical Center North Hospital
🇺🇸Richmond, Virginia, United States
Pan American Center for Oncology Trials, LLC
🇵🇷Rio Piedras, Puerto Rico