Clinical trial NCT05173298: Predictive Biomarkers in Patients With Advanced Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab
Official title: Investigation of Predictive Biomarkers in Patients With Advanced Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Advanced Hepatocellular Carcinoma
Keywords: Hepatocellular carcinoma
Lead sponsor: CHA University
Sponsor class: OTHER
Collaborators: name: Boryung Pharmaceutical Co., Ltd
First posted: 2021-12-29
Enrollment: 100
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with advanced HCC will be recruited at CHA Bundang Medical Center

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: collected tumor samples
timeFrame: through study completion, an average of 3 years
measure: collected blood samples
timeFrame: through study completion, an average of 3 years
Secondary outcomes:
measure: Multi-omics analysis
timeFrame: 3 years
measure: Biomarkers on the efficacy of Atezolizumab+Bevacizumab for advanced HCC
timeFrame: 3 years
Other outcomes:
Locations:
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Center
state: Gyeonggi-do
Study officials:
affiliation: Principal Investigator
name: Hongjae Chon, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
citation: 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.
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.
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.