Organ-specific Responses to Atezolizumab Plus Bevacizumab in Advanced HCC

March 22, 2023 updated by: CHA University

Organ-specific Responses to Atezolizumab Plus Bevacizumab in Patients With Advanced Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer-related deaths globally and in Korea. Many patients diagnosed at advanced stage, and systemic therapy is mainstay of treatment in patients with advanced HCC.

However, immune-checkpoint inhibitor (ICI) monotherapy did not significantly improve overall survival in phase III studies. According to previous retrospective analyses, ICI treatment in advanced HCC showed different organ-specific responses. The intrahepatic HCC was the least responsive organ to ICI treatment. The failure of phase III trials of ICI monotherapy may have been attributed to different organ-specific response pattern of ICIs.

Combination of atezolizumab plus bevacizumab is expected to overcome the immunosuppressive microenvironment of liver and may enhance intrahepatic response of ICI.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In a previous retrospective analysis of pembrolizumab treated patients with advanced melanoma and NSCLC, patients with liver metastases showed poorer PFS compared with those without liver metastases with reduced ORR. Similar observations have also been reported in metastatic of triple-negative breast cancer patients, there were no responses in patients with liver metastases. Taken together the results of previous studies, hepatic metastases had reduced response to ICI compared with metastases at other organs, regardless of cancer types.

In addition, ICI treatment in advanced HCC showed different organ-specific responses. The poorer response rate in liver to ICI might be affected by liver-specific immunosuppressive microenvironment (TME). To overcome the unfavorable immunosuppressive TME of the liver, combination strategies are needed to achieve enhanced anti-tumor immune responses or alleviated tumor-associated immunosuppression.

Since the cause of death in most HCC patients was hepatic failure due to intrahepatic HCC or underlying liver cirrhosis, the response rate to ICI of intrahepatic tumor lesions is a crucial factor in determining the overall prognosis of advanced HCC.

Therefore, we hypothesize that combination strategy of atezolizumab plus bevacizumab may increase organ specific response in patients with advanced HCC, and may improve survival outcomes accordingly.

Objectives We hypothesize that combination strategy of atezolizumab plus bevacizumab may increase organ specific response in patients with advanced HCC, and may improve survival outcomes accordingly.

Study Type

Observational

Enrollment (Actual)

124

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13496
        • CHA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients enrollment was performed in the CHA Bundang Medical Center, Ulsan University Hospital and Chinese University of Hong Kong

Description

Inclusion Criteria:

  • Confirmed HCC pathological or non-invasive assessment according to American Association for the Study of Liver Diseases (AASLD) criteria
  • ECOG performance status 0 or 1
  • Patients who received Atezolizumab and Bevacizumab combination therapy as first-line systemic treatment for unresectable HCC
  • Barcelona Clinic Liver Cancer (BCLC) stage B or C
  • Child-Pugh class A
  • Measurable lesion
  • Adequate hematologic and organ function

Exclusion Criteria:

  • History of autoimmune disease
  • Concomitant anticoagulation at therapeutic doses. Low dose aspirin for
  • cardio protection is permitted.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Atezolizumab plus bevacizumab
Drug: Atezolizumab plus bevacizumab
Atezolizumab plus bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Organ-specific response rate
Time Frame: 1 year
Organ-specific response rate were established to evaluate the heterogenous responses of different organ systems to immunotherapy in previous analysis. We select the largest lesions representative of involved organs (up to a maximum of two per organ and five total). Lesions of each organ were measured unidimensionally. Each lesion will be evaluated according to RECIST 1.1 (CR, complete disappearance or LN short axis diameter < 1.0cm; PR, ≥30% reduction; PD, ≥20% increase; SD, neither CR, PR nor PD). New lesions did not always indicate PD, and were added to those of the original target lesions to determine the total tumor burden.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

CHA University

Collaborators

Hoffmann-La Roche

Investigators

  • Principal Investigator: Hong Jae Chon, MD, PhD, CHA University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2021

Primary Completion (Actual)

December 31, 2022

Study Completion (Actual)

March 9, 2023

Study Registration Dates

First Submitted

April 26, 2021

First Submitted That Met QC Criteria

April 26, 2021

First Posted (Actual)

April 28, 2021

Study Record Updates

Last Update Posted (Actual)

March 23, 2023

Last Update Submitted That Met QC Criteria

March 22, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-04-010-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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