UMIN-CTR Clinical Trial

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

Hepatocellular Carcinoma

Classification by specialty

Hepato-biliary-pancreatic medicine

Hepato-biliary-pancreatic surgery

Classification by malignancy

Malignancy

Genomic information

NO

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

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)

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

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

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

Institute

National Center for Global Health and Medicine

Institute

Department

Personal name

Organization

National Center for Global Health and Medicine

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

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

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2022

Year

01

Month

15

Day

URL releasing protocol

Publication of results

Unpublished

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

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 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.

Registered date

2022

Year

01

Month

14

Day

Last modified on

2022

Year

01

Month

13

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053192