UMIN-CTR Clinical Trial

Basic information
Public title	Resection of initially unresectable hepatocellular carcinoma with atezolizumab plus bevacizumab Additional study: Identification of biomarkers for predicting therapeutic effects and adverse events
Acronym	RACB additional study
Scientific Title	Resection of initially unresectable hepatocellular carcinoma with atezolizumab plus bevacizumab Additional study: Identification of biomarkers for predicting therapeutic effects and adverse events
Scientific Title:Acronym	RACB additional study
Region	Japan

Condition
Condition	Hepatocellular Carcinoma
Classification by specialty	Hepato-biliary-pancreatic medicine Hepato-biliary-pancreatic surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	Identification of the biomarkers for atezolizumab and bevasizumab in patients with unresectable HCC
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Serum cytokine, PD-L1, PD-1, CTLA-4, Immunological evaluation of surgical specimens
Key secondary outcomes	Therapeutic effect on the imaging study, Resectability, Progression-free survival, Overall survival, Adverse event, immune-related Adverse Events (irAE)

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	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1. Diagnosed with hepatocellular carcinoma and no prior medical therapy (sorafenib, lenvatinib and immunotherapy) for hepatocellular carcinoma 2.Have at least one target lesion based on RECISTver1.1 criteria 3.Age 20 years or older 4.Eastern Cooperative Oncology Group Performance Status (PS) 0-1 5.Adequate organ function If more than one test result is present within the study period, the most recent one to enrollment should be employed, and no blood transfusion and administration of hematopoietic factor products have been performed within 30 days before the test day for measurement prior to enrollment. WBC >=3000/mm3, neutrophil count >=1500/mm3, Hb >=8.5g/dL, platelet count >=60,000/mm3, total bilirubin <=3.0 mg/dL, serum albumin >=2.8g/dL, AST (GOT), ALT (GPT) <=5 times the upper limit of each medical institution (excluding cases associated with cancer) Serum creatinine <=1.5 times the upper limit of each medical institution Urine protein<= 2+ Urine protein/creatinine ratio <2.0 at any time when urine protein is >=3+ (urine protein < 2.0g in case of 24-hour urine collection). 6.Child Pugh score of 5-6 within 14 days prior to enrollment 7.No other active malignancies 8.A patient's written informed consent (IC) has been obtained after sufficient explanation of study given to the patient. 9. Hepatocellular carcinoma tumor conditions are classified as A, B, C, D, or E. *1 Unresectable hepatocellular carcinoma.
Key exclusion criteria	1. Currently receiving oral or parenteral anticoagulants or thrombolytics within 10 days prior to enrollment. 2. Have untreated or not adequately treated esophageal varices at high risk of bleeding, or a history of bleeding due to esophageal varices within 180 days prior to enrollment. 3. Had thrombosis and/or embolism within 180 days before enrollment. 4. Has undergone major surgical procedures within 28 days before enrollment. 5. Has received systemic immunostimulatory agents within 180 days prior to enrollment. 6. Has received systemic immunosuppressants within 14 days before enrollment. 7.History and complications of autoimmune disease within 180 days prior to enrollment 8. History of active double cancer or malignancy. 9. Currently participating in another study of unapproved drugs or a study requiring intervention. 10.Critical cardiovascular disease, unstable arrhythmia or unstable angina in the 90 days prior to enrollment. 11.Pregnant, breastfeeding, positive in pregnancy test, women and men unwilling to contraceptive during the study period. 12. Has clinically uncontrolled pleural effusion, pericardial effusion or ascites. 13. Has complications of hepatic encephalopathy 14. Uncontrollable hypertension, severe infection, hemodialysis 15. Has a history of serious allergic or anaphylactic reactions to chimeric antibody, humanized antibody, or fusion protein. 16.Hypersensitivity to either Chinese hamster ovary cell-derived products or components of atezolizumab or bevacizumab products. 17.Has a history of hemorrhagic disease, gastrointestinal hemorrhage or active hemoptysis. 18. Difficult to ingest medication 19.HIV-positive 20. Active pulmonary fibrosis or interstitial pneumonia 21.Has received blood transfusions or G-CSF products within 14 days prior to enrollment 22. The attending physician judges that the patient is not suitable for participating in the study.
Target sample size	50

Research contact person
Name of lead principal investigator	1st name Kyoji Middle name Last name Ito
Organization	National Center for Global Health and Medicine
Division name	Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery
Zip code	162-8655
Address	1-21-1, Toyama, Shinjuku-ku, Tokyo
TEL	03-3202-7181
Email	kyito@hosp.ncgm.go.jp

Public contact
Name of contact person	1st name Kyoji Middle name Last name Ito
Organization	National Center for Global Health and Medicine
Division name	Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery
Zip code	162-8655
Address	1-21-1, Toyama, Shinjuku-ku, Tokyo, Japan
TEL	03-3202-7181
Homepage URL
Email	kyito@hosp.ncgm.go.jp

Sponsor
Institute	National Center for Global Health and Medicine
Institute
Department

Funding Source
Organization	National Center for Global Health and Medicine
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	National Center for Global Health and Medicine
Address	1-21-1, Toyama, Shinjuku-ku, Tokyo, Japan
Tel	03-3202-7181
Email	kenkyu-shinsa@hosp.ncgm.go.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 01 Month 15 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	Preinitiation
Date of protocol fixation	2021 Year 10 Month 10 Day
Date of IRB	2021 Year 10 Month 14 Day
Anticipated trial start date	2022 Year 01 Month 15 Day
Last follow-up date	2026 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information	1. Cytokine measurement and imaging will be performed in patients with hepatocellular carcinoma, before, 6 weeks, and 12 weeks after the start of the therapy. 2. Preoperative and postoperative cytokine measurements will be performed. 3. The relationship between biomarkers and prognosis and adverse events will be evaluated.

Management information
Registered date	2022 Year 01 Month 14 Day
Last modified on	2022 Year 01 Month 13 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053192

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name

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