Clinical trial NCT06096779: A Study Evaluating Atezolizumab, With or Without Bevacizumab, in Participants With Unresectable Hepatocellular Carcinoma and Child-Pugh B7 and B8 Cirrhosis
Official title: A Phase II, Open-Label, Multi-Cohort, Multicenter Study in Patients With Unresectable Hepatocellular Carcinoma and Child-Pugh B7 and B8 Cirrhosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Cirrhosis
liver cancer
liver tumor
Child-Pugh B
hepatocellular carcinoma
atezolizumab
bevacizumab
Immune Checkpoint Inhibitor
Digestive System Neoplasms
Kirros
ML44719
liver disease
Genentech
Immunotherapy
CPB
CPB 7
CPB 8
Tecentriq
Avastin
HCC
Cirrhotic Liver
Fatty Liver
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2023-10-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 of atezolizumab plus bevacizumab (Cohort A) or atezolizumab monotherapy (Cohort B) in this population.

Eligibility criteria: 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 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
* Absolute neutrophil count ≥1.0 x 109/L (≥1000/μL) without granulocyte colony-stimulating factor support
* Platelet count ≥ 50 × 109/L (50,000/μL) without transfusion
* Hemoglobin ≥ 80 g/L (8 g/dL) AST and ALT ≤ 5 × upper limit of normal (ULN)
* Serum bilirubin ≤ 3 × ULN
* Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula)
* Serum albumin ≥ 20 g/L (2.0 g/dL) without transfusion in the prior 3 months
* INR ≤2.3

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
* 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 within 3 months is an exclusion criteria
* Participants with ascites controlled on diuretics are allowed.
* History of spontaneous bacterial peritonitis within last 12 months

Primary outcomes:
measure: Percentage of Participants with Adverse Events
timeFrame: Baseline through the end of the study (up to approximately 36 months)
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California-Keck School of Medicine -1975 Zonal Ave
state: California
city: Newport Beach
country: United States
facility: University of Southern California
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Pasadena
country: United States
facility: California Liver Research Institute
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Health Care
state: California
city: Torrance
country: United States
facility: Harbor UCLA Medical Center
state: California
city: West Hollywood
country: United States
facility: Cedars Sinai Comprehensive Transplant Center
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers (Williams) - USOR
state: Colorado
city: Hartford
country: United States
facility: Hartford Healthcare Cancer Institute at Hartford Hospital
state: Connecticut
city: Washington
country: United States
facility: Washington DC VA Medical Center
state: District of Columbia
city: Orlando
country: United States
facility: Orlando Health Inc.
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Health Outpatient Care Center
state: Illinois
city: Chicago
country: United States
facility: The Duchossois Center for Advanced Medicine
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky - Markey Cancer Center
state: Kentucky
city: Baton Rouge
country: United States
facility: LSU Health Baton Rouge
state: Louisiana
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Physician Group
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Veterans Affairs Ann Arbor Healthcare System
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke?s Hospital of Kansas City
state: Missouri
city: Morristown
country: United States
facility: MorristownMedicalCenter
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Newark
country: United States
facility: Rutgers Cancer Institute of New Jersey at University Hospital
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Bronx
country: United States
facility: James J Peters Veterans Administration Medical Center - NAVREF
state: New York
city: Mineola
country: United States
facility: Long Island Heart Associates
state: New York
city: New Hyde Park
country: United States
facility: R.J. Zuckerberg Cancer Hospital/Northwell Health - BRANY - PPDS
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Dayton
country: United States
facility: Dayton VA Medical Center - NAVREF - PPDS
state: Ohio
city: Oklahoma City
country: United States
facility: The University of Oklahoma Health Sciences Center
state: Oklahoma
city: Hillsboro
country: United States
facility: Kaiser Permanente Westside Medical Center
state: Oregon
city: Portland
country: United States
facility: OHSU Knight Cancer Institute Hematology Oncology
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Veterans Affairs Pittsburgh Healthcare System - NAVREF - PPDS
state: Pennsylvania
city: Germantown
country: United States
facility: The West Clinic (East Campus)
state: Tennessee
city: Nashville
country: United States
facility: Nashville General Hospital at Meharry
state: Tennessee
city: Dallas
country: United States
facility: Liver Institute at Methodist Dallas
state: Texas
city: Dallas
country: United States
facility: Moody Outpatient Center ? Parkland Health
state: Texas
city: Dallas
country: United States
facility: Texas Oncology (Worth) - USOR
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Denison
country: United States
facility: Texas Oncology - Denison Cancer Center
state: Texas
city: Houston
country: United States
facility: Kelsey Research Foundation
state: Texas
city: Houston
country: United States
facility: Michael E Debakey VA Medical Center - NAVREF - PPDS
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Murray
country: United States
facility: Intermountain Healthcare
state: Utah
city: Saint George
country: United States
facility: Intermountain Cancer Center
state: Utah
city: Falls Church
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Newport News
country: United States
facility: Maryview Hospital, Inc.
state: Virginia
city: Richmond
country: United States
facility: Bon Secours St. Mary's Hospital
state: Virginia
city: Richmond
country: United States
facility: VCU Medical Center North Hospital
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: