A Study Evaluating Atezolizumab, With or Without Bevacizumab, in Participants With Unresectable Hepatocellular Carcinoma and Child-pugh B7 and B8 Cirrhosis
Atezolizumab: Atezolizumab will be administered at a dose of 1200 milligrams (mg) by intravenous (IV) infusion on Day 1 of each 21-day cycle.
Bevacizumab: Bevacizumab will be administered at a dose of 15 milligrams per kilogram (mg/kg) by IV infusion on Day 1 of each 21-day cycle.
Study summary
The purpose of this study is to assess the safety 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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 participants
* 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 Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
* Eastern Cooperative Oncology Group (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
* Absolute neutrophil count ≥1.0 x 10\^9 per liter (/L) (≥1000 per microliter \[/μL\]) without granulocyte colony-stimulating factor support
* Platelet count ≥ 50 × 109/L (50,000/μL) without transfusion
* Hemoglobin ≥ 80 grams per liter (g/L) (8 grams per deciliter \[g/dL\]) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × upper limit of normal (ULN)
* Serum bilirubin ≤ 3 × ULN
* Creatinine clearance ≥ 50 milliliters per minute (mL/min) (calculated using the Cockcroft-gault formula)
* Serum albumin ≥ 20 g/L (2.0 g/dL) without transfusion in the prior 3 months
* International normalized ratio (INR) ≤2.3
General Exclusion Criteria:
* Pregnancy or breastfeeding
* Prior treatment with cluster of differentiation 137 (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
* Participants 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
* Participants on preventative hormonal therapies (i.e., tamoxifen and other hormonal inhibitors) are not excluded
* 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
* Actively 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
* Hepatic encephalopathy is allowed if no active symptoms or stable within 3 months of study treatment
* History, planned, or recommended placement of transjugular intrahepatic portosystemic shunt (TIPS) is excluded from Cohort A only. TIPS is acceptable in Cohort B
* Diagnostic paracentesis is allowed. Therapeutic paracentesis: one large volume paracentesis prior to enrollment with diuretic controlled ascites is allowed.
* Participants with ascites controlled on diuretics are allowed
* History of spontaneous bacterial peritonitis within last 12 months
Primary outcome measure(s)
Percentage of Participants With Adverse Events (AEs) — Baseline through the end of the study (up to approximately 36 months) An AE is any untoward medical occurrence in a participant 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 Cohorts A and B.
Trial sites (59)
Facility
City
Region
Status
University of Arizona Cancer Center
Tucson
Arizona
UC San Diego Moores Cancer Center
La Jolla
California
University of Southern California-Keck School of Medicine -1975 Zonal Ave
Los Angeles
California
University of Southern California
Newport Beach
California
University of California Irvine Medical Center
Orange
California
California Liver Research Institute
Pasadena
California
University of California Davis Medical Center
Sacramento
California
Stanford Health Care
Stanford
California
Harbor UCLA Medical Center
Torrance
California
Cedars Sinai Comprehensive Transplant Center
West Hollywood
California
Rocky Mountain Cancer Centers (Williams) - USOR
Denver
Colorado
Hartford Healthcare Cancer Institute at Hartford Hospital
Hartford
Connecticut
George Washington University- Medical Faculty Associates
Washington D.C.
District of Columbia
Washington DC VA Medical Center
Washington D.C.
District of Columbia
Orlando Health Inc.
Orlando
Florida
Northwestern University
Chicago
Illinois
University of Illinois Health Outpatient Care Center
Chicago
Illinois
The Duchossois Center for Advanced Medicine
Chicago
Illinois
University of Kentucky - Markey Cancer Center
Lexington
Kentucky
LSU Health Baton Rouge
Baton Rouge
Louisiana
Our Lady of the Lake Cancer Institute
Baton Rouge
Louisiana
Tufts Medical Center
Boston
Massachusetts
Beth Israel Deaconess Medical Center
Boston
Massachusetts
Veterans Affairs Ann Arbor Healthcare System
Ann Arbor
Michigan
Barbara Ann Karmanos Cancer Institute
Detroit
Michigan
Henry Ford Health System
Detroit
Michigan
Saint Luke?s Hospital of Kansas City
Kansas City
Missouri
MorristownMedicalCenter
Morristown
New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick
New Jersey
Rutgers Cancer Institute of New Jersey at University Hospital
Newark
New Jersey
NYU Langone Hospital - Long Island
Mineola
New York
NYU Langone Medical Center
New York
New York
Icahn School of Medicine at Mount Sinai
New York
New York
Montefiore Medical Center
The Bronx
New York
James J Peters Veterans Administration Medical Center - NAVREF
The Bronx
New York
Levine Cancer Institute
Charlotte
North Carolina
Dayton VA Medical Center - NAVREF - PPDS
Dayton
Ohio
The University of Oklahoma Health Sciences Center
Oklahoma City
Oklahoma
Kaiser Permanente Westside Medical Center
Hillsboro
Oregon
OHSU Knight Cancer Institute Hematology Oncology
Portland
Oregon
+ 19 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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