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Organ-specific Responses to Atezolizumab Plus Bevacizumab in Advanced HCC

Sponsor
CHA University (Other)
Overall Status
Recruiting
CT.gov ID
NCT04862949
Collaborator
Hoffmann-La Roche (Industry)
100
Enrollment
1
Location
12
Anticipated Duration (Months)
8.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Atezolizumab plus bevacizumab

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 Design

Study Type:
Observational
Anticipated Enrollment :
100 participants
Observational Model:
Cohort
Time Perspective:
Retrospective
Official Title:
Organ-specific Responses to Atezolizumab Plus Bevacizumab in Patients With Advanced Hepatocellular Carcinoma
Actual Study Start Date :
May 1, 2021
Anticipated Primary Completion Date :
Feb 28, 2022
Anticipated Study Completion Date :
Apr 30, 2022

Arms and Interventions

Arm Intervention/Treatment
Atezolizumab plus bevacizumab

Atezolizumab plus bevacizumab

Drug: Atezolizumab plus bevacizumab
Atezolizumab plus bevacizumab

Outcome Measures

Primary Outcome Measures

  1. Organ-specific response rate [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
19 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Cha Medical Center Seongnam-si Gyeonggi-do Korea, Republic of 13496

Sponsors and Collaborators

  • CHA University
  • Hoffmann-La Roche

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
CHA University
ClinicalTrials.gov Identifier:
NCT04862949
Other Study ID Numbers:
  • 2021-04-010-001
First Posted:
Apr 28, 2021
Last Update Posted:
Feb 24, 2022
Last Verified:
Apr 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by CHA University
Hepatocellular carcinoma, atezolizumab, bevacizumab
Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Bevacizumab
Atezolizumab

Study Results

No Results Posted as of Feb 24, 2022