UMIN-CTR Clinical Trial

Basic information
Public title	Exploratory biomarker study on tumor microenvironment using pre-treatment and refractory archival samples of hepatocellular carcinoma
Acronym	Exploratory biomarker study on tumor microenvironment by archival samples of hepatocellular carcinoma
Scientific Title	Exploratory biomarker study on tumor microenvironment using pre-treatment and refractory archival samples of hepatocellular carcinoma
Scientific Title:Acronym	Exploratory biomarker study on tumor microenvironment by archival samples of hepatocellular carcinoma
Region	Japan

Condition
Condition	Unresectable hepatocellular carcinoma
Classification by specialty	Gastroenterology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	Using archival samples (tumor and non-tumor tissue samples, blood samples) of hepatocellular carcinoma patients who received atezolizumab plus bevacizumab or molecular targeted drugs (sorafenib, lenvatinib) in unresectable HCC first-line therapy, we will comprehensively analyze the clinical course and changes in tumor microenvironment and metabolic environment before and after drug treatment. By comparing clinical data such as treatment response, we will explore changes in the tumor microenvironment, including predictors of efficacy and mechanisms of drug resistance.
Basic objectives2	Others
Basic objectives -Others	Correlation of the efficacy of atezolizumab plus bevacizumab combination therapy to the tumor microenvironment and metabolic milieu and pre- and post-treatment changes.
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Correlation between the efficacy of atezolizumab + bevacizumab combination therapy (response, early PD) and tumor microenvironment (PD-1 positive effector T cells, PD-1 positive regulatory T cells, CD36 positive regulatory T cells, angiogenesis and lymphangiogenesis) and metabolic environment (concentration of fatty acids etc.) and pre- and post-treatment changes.
Key secondary outcomes	Correlation between the efficacy and etiology of liver (metabolic environment), correlation between atezolizumab + bevacizumab combination therapy and the signature of oncogene expression and pre- and post-treatment changes. Relation of the efficacy of the molecularly targeted agents lenvatinib and sorafenib to the tumor microenvironment and metabolic environment and pre- and post-treatment changes. Relation between the efficacy of the molecularly targeted agents lenvatinib and sorafenib before and after treatment and the signatures of oncogene expression in the etiology of liver and changes in the metabolic environment.

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	Not applicable
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Patients in clinical research approved by the Ethics Review Committee of the Graduate School of Medicine, Chiba University, who have given consent in opt-out form via an information disclosure document, who meet the following eligibility criteria, and who have secondary available archival samples (tumor/non-tumor tissue samples, blood samples). 1) Unresectable hepatocellular carcinoma 2) Receiving lenvatinib, sorafenib, or atezolizumab plus bevacizumab as first-line treatment (excluding hepatic arterial infusion or hepatic arterial chemoembolization)
Key exclusion criteria	Patients who do not meet the inclusion criteria.
Target sample size	60

Research contact person
Name of lead principal investigator	1st name Naoya Middle name Last name Kato
Organization	Chiba University Hospital
Division name	Department of Gastroenterology
Zip code	260-8677
Address	1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, JAPAN
TEL	043-222-7171
Email	kato.naoya@chiba-u.jp

Public contact
Name of contact person	1st name Sadahisa Middle name Last name Ogasawara
Organization	Chiba University Hospital
Division name	Department of Gastroenterology
Zip code	260-8677
Address	1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, JAPAN
TEL	043-222-7171
Homepage URL
Email	kato.naoya@chiba-u.jp

Sponsor
Institute	Chiba University Hospital
Institute
Department

Funding Source
Organization	Chugai Pharmaceutical Co., Ltd.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor	Chugai Pharmaceutical Co., Ltd.
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Ethics Review Committee of the Graduate School of Medicine, Chiba University
Address	1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, JAPAN
Tel	043-222-7171
Email	inohana-rinri@chiba-u.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2022 Year 05 Month 10 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Enrolling by invitation
Date of protocol fixation	2022 Year 01 Month 06 Day
Date of IRB	2021 Year 12 Month 14 Day
Anticipated trial start date	2022 Year 01 Month 06 Day
Last follow-up date	2024 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other

Other related information

Patients in clinical research approved by the Ethics Review Committee of the Graduate School of Medicine, Chiba University, who have given consent in opt-out form via an information disclosure document, who meet the following eligibility criteria, and who have secondary available archival samples (tumor/non-tumor tissue samples, blood samples). 1) Unresectable hepatocellular carcinoma 2) Receiving lenvatinib, sorafenib, or atezolizumab plus bevacizumab as first-line treatment (excluding hepatic arterial infusion or hepatic arterial chemoembolization)

Management information
Registered date	2022 Year 05 Month 10 Day
Last modified on	2022 Year 05 Month 10 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000054386