Predictive Biomarkers in Patients With Advanced Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab

Advanced Hepatocellular Carcinoma Clinical Trial

— HCC  

Official title:

Investigation of Predictive Biomarkers in Patients With Advanced Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05173298
• Other study ID #: 2021-07-080
• Status: Recruiting
• Start date: August 2, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: CHA University
• Contact: Hong Jae Chon, MD,PhD
• Phone: 82-031-780-3928
• Email: minidoctor[@]cha.ac.kr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this observational study is to learn about in patients with advanced hepatocellular carcinoma treated with atezoliozumab and bevacizumab.

In this clinical study, we intend to analyze the multiomics data by analyzing the peripheral blood and tumor tissue before and after treatment of patients with advanced liver cancer receiving systemic drug treatment, and analyzing the correlation with the treatment. This is an exploratory study that aims to discover biomarkers that are highly correlated with treatment response.

Description:

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide, and HCC is more frequently observed in Asia, including South Korea. As HCC is often accompanied by chronic hepatitis B or C virus and liver cirrhosis, treatment of HCC consider not only the tumor but also various factors such as liver function and the patient's performance status. Local treatment and surgery are possible in the early stages of HCC. However, it has a high recurrence rate even after curative surgeries due to underlying cirrhosis and the tumor microenvironment.

Although several studies have investigated gene mutations and differences in treatment response in advanced HCC through next-generation sequencing (NGS), studies on transcriptome analysis of advanced HCC through RNA-sequencing are hard to find, with a need for future research into precise classification and clinical significance of HCC based on multi-omics data to establish multi-omics data and discover biomarkers highly associated with treatment response in HCC patients who received atezolizumab and bevacizumab combination.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

The following two groups will be integrated and analyzed. The criteria for both groups are the same.

Group 1. Prospective Group

Inclusion Criteria

• Those above the age of 20 who understand the purpose of the study and agree to participate in the collection of samples during the study.

• Patients who have been diagnosed with unresectable advanced HCC through imaging, histological, or cytological tests.

• Patients who underwent an NGS test with advanced HCC tissues

• Patients planning to receive atezolizumab and bevacizumab combination therapy

• Patients with measurable lesions based on RECIST v1.1

• ECOG performance status 0 or 1

• Patients with a life expectancy of at least three months

Exclusion Criteria

• Patients who have systemic conditions accompanied by instability of vital signs, such as infections or organ failure

• Those with mental/neurological conditions or dementia who have difficulties understanding and completing the consent form

• Those who are assessed as not suitable for this study, at the discretion of the researcher

Group 2. Retrospective Group

Inclusion Criteria

• Those above the age of 20 who understand the purpose of the study and agree to participate in the collection of samples during the study.

• Patients who have been diagnosed with unresectable advanced HCC through imaging, histological, or cytological tests.

• Patients who underwent an NGS test with advanced HCC tissues

• Patients have received atezolizumab and bevacizumab combination therapy

• Patients with measurable lesions based on RECIST v1.1

• ECOG performance status 0 or 1

• Patients with a life expectancy of at least three months

Exclusion criteria

• Patients who have systemic conditions accompanied by instability of vital signs, such as infections or organ failure

• Those with mental/neurological conditions or dementia who have difficulties understanding and completing the consent form

• Those who are assessed as not suitable for this study, at the discretion of the researcher

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• atezolizumab plus bevacizumab
1200 mg of atezolizumab plus 15 mg/kg of body weight of bevacizumab intravenously every 3 weeks

Locations

Country	Name	City	State
Korea, Republic of	CHA Bundang Medical Center	Seongnam-si	Gyeonggi-do

Sponsors (2)

Lead Sponsor	Collaborator
CHA University	Boryung Pharmaceutical Co., Ltd

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (7)

Boyault S, Rickman DS, de Reynies A, Balabaud C, Rebouissou S, Jeannot E, Herault A, Saric J, Belghiti J, Franco D, Bioulac-Sage P, Laurent-Puig P, Zucman-Rossi J. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology. 2007 Jan;45(1):42-52. doi: 10.1002/hep.21467. — View Citation

Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745. — View Citation

Hoshida Y, Toffanin S, Lachenmayer A, Villanueva A, Minguez B, Llovet JM. Molecular classification and novel targets in hepatocellular carcinoma: recent advancements. Semin Liver Dis. 2010 Feb;30(1):35-51. doi: 10.1055/s-0030-1247131. Epub 2010 Feb 19. — View Citation

Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1. — View Citation

Llovet JM, Montal R, Sia D, Finn RS. Molecular therapies and precision medicine for hepatocellular carcinoma. Nat Rev Clin Oncol. 2018 Oct;15(10):599-616. doi: 10.1038/s41571-018-0073-4. — View Citation

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. — View Citation

Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C, Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele B, Webber AL, Ebbinghaus SW, Ma J, Siegel AB, Cheng AL, Kudo M; KEYNOTE-224 investigators. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018 Jul;19(7):940-952. doi: 10.1016/S1470-2045(18)30351-6. Epub 2018 Jun 3. Erratum In: Lancet Oncol. 2018 Sep;19(9):e440. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	collected tumor samples	tumor samples from patients with hepatocellular carcinoma (incidence of analysis of the expression patterns of various immune response-related proteins through H&E staining, immunochemical staining, and immunofluorescent staining methods, association with treatment response and survival duration)	through study completion, an average of 3 years
Primary	collected blood samples	blood samples from patients with hepatocellular carcinoma (incidence of Flow cytometry, ELISA analysis, single cell RNA sequencing, association with treatment response and survival duration	through study completion, an average of 3 years
Secondary	Multi-omics analysis	Multi-omics analysis to further subtype and find therapeutic targets of HCC Multi-omics analysis is a total and integrated analysis of various molecular levels such as dielectric and protein.	3 years
Secondary	Biomarkers on the efficacy of Atezolizumab+Bevacizumab for advanced HCC	Molecular biomarker associated with overall survival, progression-free survival and objective response rate in patients who receive atezolizumab plus bevacizumab A gene-based biomarker that predicts the therapeutic response of patients administered with Atezolizumab and Bevacizumab.	3 years