Dysautonomia International

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

Purpose

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.

Condition

Hepatocellular Carcinoma

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

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

Study Design

Phase: Phase 2
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Cohort A: Atezolizumab+Bevacizumab	Participants will receive atezolizumab plus bevacizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator.	Drug: Atezolizumab Atezolizumab will be administered at a dose of 1200 milligrams (mg) by intravenous (IV) infusion on Day 1 of each 21-day cycle. Other names: Tecentriq; RO5541267 Drug: 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. Other names: Avastin; RO4876646
Experimental Cohort B: Atezolizumab	Participants will receive atezolizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator.	Drug: Atezolizumab Atezolizumab will be administered at a dose of 1200 milligrams (mg) by intravenous (IV) infusion on Day 1 of each 21-day cycle. Other names: Tecentriq; RO5541267

Recruiting Locations

University of Arizona Cancer Center
Tucson, Arizona 85724

UC San Diego Moores Cancer Center
La Jolla, California 92093

University of Southern California-Keck School of Medicine -1975 Zonal Ave
Los Angeles, California 90089-5601

University of Southern California
Newport Beach, California 92663

California Liver Research Institute
Pasadena, California 91105-2561

Stanford Health Care
Stanford, California 94305

Harbor UCLA Medical Center
Torrance, California 90502-2006

Cedars Sinai Comprehensive Transplant Center
West Hollywood, California 90048-2422

Rocky Mountain Cancer Centers (Williams) - USOR
Denver, Colorado 80218-1237

Hartford Healthcare Cancer Institute at Hartford Hospital
Hartford, Connecticut 06106

Washington DC VA Medical Center
Washington D.C., District of Columbia 20422-0001

Orlando Health Inc.
Orlando, Florida 32806

Northwestern University
Chicago, Illinois 60611-2908

University of Illinois Health Outpatient Care Center
Chicago, Illinois 60612-4795

The Duchossois Center for Advanced Medicine
Chicago, Illinois 60637-1426

University of Kentucky - Markey Cancer Center
Lexington, Kentucky 40536-7001

LSU Health Baton Rouge
Baton Rouge, Louisiana 70805

Our Lady of the Lake Cancer Institute
Baton Rouge, Louisiana 70808-4300

Tufts Medical Center
Boston, Massachusetts 02111

Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215

Veterans Affairs Ann Arbor Healthcare System
Ann Arbor, Michigan 48105

Barbara Ann Karmanos Cancer Institute
Detroit, Michigan 48201

Henry Ford Health System
Detroit, Michigan 48202

Saint Luke?s Hospital of Kansas City
Kansas City, Missouri 64111

MorristownMedicalCenter
Morristown, New Jersey 07962

Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey 08901

Rutgers Cancer Institute of New Jersey at University Hospital
Newark, New Jersey 07103

Long Island Heart Associates
Mineola, New York 11501-4298

NYU Langone Medical Center
New York, New York 10016-9451

Icahn School of Medicine at Mount Sinai
New York, New York 10029

Montefiore Medical Center
The Bronx, New York 10467

James J Peters Veterans Administration Medical Center - NAVREF
The Bronx, New York 10468-3904

Levine Cancer Institute
Charlotte, North Carolina 28204

Dayton VA Medical Center - NAVREF - PPDS
Dayton, Ohio 45428-9000

The University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104-5020

Kaiser Permanente Westside Medical Center
Hillsboro, Oregon 97124-5806

OHSU Knight Cancer Institute Hematology Oncology
Portland, Oregon 97239-3011

Jefferson Health Honickman Center
Philadelphia, Pennsylvania 19107

Nashville General Hospital at Meharry
Nashville, Tennessee 37208-2918

Liver Institute at Methodist Dallas
Dallas, Texas 75203-1260

Moody Outpatient Center ? Parkland Health
Dallas, Texas 75235

Texas Oncology (Worth) - USOR
Dallas, Texas 75246-2008

University of Texas Southwestern Medical Center
Dallas, Texas 75390-0001

Texas Oncology - Denison Cancer Center
Denison, Texas 75020-0084

Kelsey Research Foundation
Houston, Texas 77025-1669

Michael E Debakey VA Medical Center - NAVREF - PPDS
Houston, Texas 77030-4211

Houston Methodist Hospital
Houston, Texas 77030

Intermountain Healthcare
Murray, Utah 84107-5741

Intermountain Cancer Center
St. George, Utah 84790

Bon Secours St. Mary's Hospital
Richmond, Virginia 23226-1925

VCU Medical Center North Hospital
Richmond, Virginia 23298-5028

Virginia Mason Medical Center
Seattle, Washington 98101

Pan American Center for Oncology Trials, LLC
Rio Piedras, Puerto Rico 00935

More Details

Status: Recruiting
Sponsor: Genentech, Inc.

Study Contact

Reference Study ID Number: ML44719 https://forpatients.roche.com/
888-662-6728 (U.S. and Canada)
global-roche-genentech-trials@gene.com

Detailed Description

This is a Phase II, open-label, multicohort, multicenter study in participants with unresectable, locally advanced, or metastatic 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.