Phase II Study of Unresectable Hepatocellular Carcinoma and Cirrhosis

What is the Purpose of this Study?

The purpose of this study is to evaluate the effects of combined immunotherapy regimens (atezolizumab with bevacizumab) in patients with inoperable liver cancer and liver disease (cirrhosis). Participants may receive atezolizumab alone (if they are ineligible or could not tolerate bevacizumab). The study also aims to determine whether a biomarker test can help scientists learn more about the treatment response, prediction for progression, and drug safety in relation to liver cancer and other diseases; possible links among diseases; and new avenues for drug development and personalized therapies. A biomarker is a biological molecule found in blood, other body fluids or tissues that may be a sign of a condition or disease. Atezolizumab with bevacizumab has been approved by the U.S. Food and Drug Administration (FDA); this combination can be given for the treatment of inoperable or advanced liver cancer in patients who have not received prior systemic treatment. However, patients with diminished liver functions are notably excluded from receiving those regimens for unresectable hepatocellular carcinoma (tumor or lesion that is unable to be removed with surgery).

Eligibility

* 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

* 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
* 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

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

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

Study Details

Disease Type/Condition

Other

Principal Investigator

Yang, Ju Dong

Co-Investigators

Emily Kaymen

Age Group

Adult

Phase

IRB Number

STUDY00003625

ClinicalTrials.gov ID

NCT06096779

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org