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Bevacizumab in Combination With Sintilimab Versus Transcatheter Arterial Chemoembolization for the Treatment of Intermediate Stage Hepatocellular Carcinoma (Beyond Up-To-Seven Criteria) (BEST)

Primary Purpose

Hepatocellular Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Bevacizumab combined with Sintilimab
Transcatheter arterial chemoembolization
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Histologically confirmed hepatocellular carcinoma, or meet the American Association for the Study of Liver Diseases (AASLD) clinical diagnostic criteria for hepatocellular carcinoma. Age ≥ 18 years old. ECOG score 0. No systemic systemic antitumor therapy against hepatocellular carcinoma and transhepatic arterial intervention prior to treatment. Tumour extent: Barcelona Clinic Liver Cancer (BCLC) stage B unsuitable for radical surgery and/or local treatment, together with a tumour load exceeding the Up-To-Seven criteria, i.e. the sum of the size (in centimetres) of the largest tumour in the liver and the number of tumours greater than 7; tumor was bilobed with multiple lesions; at least one measurable lesion with CT/MRI showing arterial phase enhancement; no portal vein thrombus; and no extrahepatic metastasis. No risk of variceal bleeding: CT/MRI/esophagogastroduodenoscopy within 6 months did not suggest esophagogastric fundic varices and active ulcers. Child-Push A Normal hematologic function (platelets >75×10E9/L; leukocytes >3.0×10E9/L; neutrophils >1.5×10E9/L) Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN), transaminases ≤ 3 times the ULN No ascites, normal coagulation function, albumin ≥ 30g/L Serum creatinine less than 1.5 times the upper limit of normal (ULN) Life expectancy > 3 months Exclusion Criteria: Previously confirmed fibrous lamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and bile duct carcinoma. history of hepatic encephalopathy or a history of liver transplantation. pleural fluid, ascites, and pericardial effusion with clinical symptoms requiring drainage. Acute or chronic active hepatitis B or C infection with hepatitis B virus (HBV) DNA > 2000 IU/ml or 10E4 copies/ml; hepatitis C virus (HCV) RNA > 10E3 copies/ml; positive for both hepatitis B surface antigen (HbsAg) and anti-HCV antibodies. Those who were below the above criteria after antiviral therapy could be enrolled. had any of the following within the 12 months prior to study entry: myocardial infarction, severe/unstable angina, coronary artery bypass graft, congestive heart failure, cerebrovascular accident (including transient ischemic attack), pulmonary embolism; ongoing: arrhythmia ≥ grade 2 according to NCI-CTCAE criteria, prolonged QTc interval (>450 ms in men , women >470 ms); Uncontrollable hypertension, systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy. Renal failure requiring hemodialysis or peritoneal dialysis; Severe dysfunction of other vital organs; History of malignancy other than hepatocellular carcinoma within 3 years prior to screening, except for malignancies with negligible risk of metastasis or death (e.g., 5-year OS rate >90%), such as adequately treated cervical carcinoma in situ, non-melanoma skin cancer, limited prostate cancer, ductal carcinoma in situ, or stage I uterine cancer; evidence of brain or soft meningeal lesions; hemophilia or bleeding tendencies, who are taking therapeutic doses of anticoagulant therapy such as coumarin derivative drugs; pregnant or lactating females, all female patients of childbearing potential must have a pregnancy test (serum or urine) within 7 days prior to enrollment and have a negative result; Prior organ transplant history; Known HIV infection; Active Tuberculosis chemotherapy drug allergy; comorbid systemic or other serious co-morbidities that, in the judgment of the investigator, would make the patient unsuitable for participation in this study or substantially interfere with the appropriate assessment of the safety and toxicity of the prescribed protocol. Active or history of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, dry syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with other serious acute, chronic physical or psychiatric illnesses or abnormal laboratory tests that may increase the risk associated with study participation or that may interfere with the interpretation of study results or that the investigator deems unsuitable for enrollment. Patients with any history of significant noncompliance with medical regimens or inability to obtain reliable informed consent.

Sites / Locations

  • Sun Yat-Sen University Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Bevacizumab combined with Sintilimab

Transcatheter arterial chemoembolization

Arm Description

Bevacizumab combined with sintilimab, sindilizumab 200 mg IV d1, Q3W, combined with bevacizumab 15 mg/kg IV d1, Q3W treatment, treatment continued until disease progression, development of intolerable toxic reactions

Transcatheter arterial chemoembolization, patients were treated with cTACE, and the efficacy was assessed by repeat CT/MRI 1 month after the initial treatment, and if the tumor still had arterial phase enhancement, TACE treatment could be supplemented until treatment failure and withdrawal of consent.

Outcomes

Primary Outcome Measures

progression free survival,PFS
Assessed using the mRECIST criteria, defined as patient survival without tumor progression from the start of randomization to the end of year 2

Secondary Outcome Measures

overall survival, OS
Defined as the time from the start of randomization to death from any cause.
post-progression survival,PPS
Defined as overall survival minus progression-free survival time
Time to failure of treatment strategy
Time from randomization to death or need for further treatment options
Duration of Response, DOR
Time from initial response to disease progression or death in patients identified as CR or PR according to mRECIST and RECIST 1.1 criteria
objective response rate,ORR
Evaluated according to the criteria for evaluating efficacy in solid tumors (mRECIST and RECIST 1.1)
conversion rate to resection
Rate of patients whose tumors regressed and underwent surgical resection
Patient-reported outcomes, PRO
Change from baseline in overall health, quality of life, physical, role, emotional, and social functioning using the IL42-EORTCQLQ-C30 scale

Full Information

First Posted
October 14, 2023
Last Updated
October 14, 2023
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT06090656
Brief Title
Bevacizumab in Combination With Sintilimab Versus Transcatheter Arterial Chemoembolization for the Treatment of Intermediate Stage Hepatocellular Carcinoma (Beyond Up-To-Seven Criteria)
Acronym
BEST
Official Title
Bevacizumab in Combination With Sintilimab Versus Transcatheter Arterial Chemoembolization for the Treatment of Intermediate Stage Hepatocellular Carcinoma (Beyond Up-To-Seven Criteria), A Prospective, Randomized, Controlled Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 24, 2023 (Anticipated)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Transcatheter arterial chemoembolization (TACE) is recommended as the standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) (i.e., BCLC stage B). However, these patients is heterogeneous in terms of liver functional, tumor size and tumor number, and not all patients with mid-stage HCC will benefit from TACE. The ORIENT-32 trial confirmed the efficacy of sintilimab in combination with bevacizumab for unresectable hepatocellular carcinoma. No study has yet explored whether this regimen is appropriate for patients with BCLC stage B. The purpose of this study is to explore whether bevacizumab in combination with sintilimab is superior to conventional TACE therapy in patients with HCC with beyond-Up-to-seven criteria.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
88 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Bevacizumab combined with Sintilimab
Arm Type
Active Comparator
Arm Description
Bevacizumab combined with sintilimab, sindilizumab 200 mg IV d1, Q3W, combined with bevacizumab 15 mg/kg IV d1, Q3W treatment, treatment continued until disease progression, development of intolerable toxic reactions
Arm Title
Transcatheter arterial chemoembolization
Arm Type
Sham Comparator
Arm Description
Transcatheter arterial chemoembolization, patients were treated with cTACE, and the efficacy was assessed by repeat CT/MRI 1 month after the initial treatment, and if the tumor still had arterial phase enhancement, TACE treatment could be supplemented until treatment failure and withdrawal of consent.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab combined with Sintilimab
Intervention Description
Bevacizumab combined with sintilimab, sindilizumab 200 mg IV d1, Q3W, combined with bevacizumab 15 mg/kg IV d1, Q3W treatment, treatment continued until disease progression, development of intolerable toxic reactions
Intervention Type
Procedure
Intervention Name(s)
Transcatheter arterial chemoembolization
Intervention Description
Transcatheter arterial chemoembolization, patients were treated with cTACE, and the efficacy was assessed by repeat CT/MRI 1 month after the initial treatment, and if the tumor still had arterial phase enhancement, TACE treatment could be supplemented until treatment failure and withdrawal of consent.
Primary Outcome Measure Information:
Title
progression free survival,PFS
Description
Assessed using the mRECIST criteria, defined as patient survival without tumor progression from the start of randomization to the end of year 2
Time Frame
24 months
Secondary Outcome Measure Information:
Title
overall survival, OS
Description
Defined as the time from the start of randomization to death from any cause.
Time Frame
24 months
Title
post-progression survival,PPS
Description
Defined as overall survival minus progression-free survival time
Time Frame
24 months
Title
Time to failure of treatment strategy
Description
Time from randomization to death or need for further treatment options
Time Frame
24 months
Title
Duration of Response, DOR
Description
Time from initial response to disease progression or death in patients identified as CR or PR according to mRECIST and RECIST 1.1 criteria
Time Frame
24 months
Title
objective response rate,ORR
Description
Evaluated according to the criteria for evaluating efficacy in solid tumors (mRECIST and RECIST 1.1)
Time Frame
24 months
Title
conversion rate to resection
Description
Rate of patients whose tumors regressed and underwent surgical resection
Time Frame
24 months
Title
Patient-reported outcomes, PRO
Description
Change from baseline in overall health, quality of life, physical, role, emotional, and social functioning using the IL42-EORTCQLQ-C30 scale
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed hepatocellular carcinoma, or meet the American Association for the Study of Liver Diseases (AASLD) clinical diagnostic criteria for hepatocellular carcinoma. Age ≥ 18 years old. ECOG score 0. No systemic systemic antitumor therapy against hepatocellular carcinoma and transhepatic arterial intervention prior to treatment. Tumour extent: Barcelona Clinic Liver Cancer (BCLC) stage B unsuitable for radical surgery and/or local treatment, together with a tumour load exceeding the Up-To-Seven criteria, i.e. the sum of the size (in centimetres) of the largest tumour in the liver and the number of tumours greater than 7; tumor was bilobed with multiple lesions; at least one measurable lesion with CT/MRI showing arterial phase enhancement; no portal vein thrombus; and no extrahepatic metastasis. No risk of variceal bleeding: CT/MRI/esophagogastroduodenoscopy within 6 months did not suggest esophagogastric fundic varices and active ulcers. Child-Push A Normal hematologic function (platelets >75×10E9/L; leukocytes >3.0×10E9/L; neutrophils >1.5×10E9/L) Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN), transaminases ≤ 3 times the ULN No ascites, normal coagulation function, albumin ≥ 30g/L Serum creatinine less than 1.5 times the upper limit of normal (ULN) Life expectancy > 3 months Exclusion Criteria: Previously confirmed fibrous lamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and bile duct carcinoma. history of hepatic encephalopathy or a history of liver transplantation. pleural fluid, ascites, and pericardial effusion with clinical symptoms requiring drainage. Acute or chronic active hepatitis B or C infection with hepatitis B virus (HBV) DNA > 2000 IU/ml or 10E4 copies/ml; hepatitis C virus (HCV) RNA > 10E3 copies/ml; positive for both hepatitis B surface antigen (HbsAg) and anti-HCV antibodies. Those who were below the above criteria after antiviral therapy could be enrolled. had any of the following within the 12 months prior to study entry: myocardial infarction, severe/unstable angina, coronary artery bypass graft, congestive heart failure, cerebrovascular accident (including transient ischemic attack), pulmonary embolism; ongoing: arrhythmia ≥ grade 2 according to NCI-CTCAE criteria, prolonged QTc interval (>450 ms in men , women >470 ms); Uncontrollable hypertension, systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy. Renal failure requiring hemodialysis or peritoneal dialysis; Severe dysfunction of other vital organs; History of malignancy other than hepatocellular carcinoma within 3 years prior to screening, except for malignancies with negligible risk of metastasis or death (e.g., 5-year OS rate >90%), such as adequately treated cervical carcinoma in situ, non-melanoma skin cancer, limited prostate cancer, ductal carcinoma in situ, or stage I uterine cancer; evidence of brain or soft meningeal lesions; hemophilia or bleeding tendencies, who are taking therapeutic doses of anticoagulant therapy such as coumarin derivative drugs; pregnant or lactating females, all female patients of childbearing potential must have a pregnancy test (serum or urine) within 7 days prior to enrollment and have a negative result; Prior organ transplant history; Known HIV infection; Active Tuberculosis chemotherapy drug allergy; comorbid systemic or other serious co-morbidities that, in the judgment of the investigator, would make the patient unsuitable for participation in this study or substantially interfere with the appropriate assessment of the safety and toxicity of the prescribed protocol. Active or history of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, dry syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with other serious acute, chronic physical or psychiatric illnesses or abnormal laboratory tests that may increase the risk associated with study participation or that may interfere with the interpretation of study results or that the investigator deems unsuitable for enrollment. Patients with any history of significant noncompliance with medical regimens or inability to obtain reliable informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wei He
Phone
15521248313
Email
hewei@sysucc.org.cn
Facility Information:
Facility Name
Sun Yat-Sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei He
Phone
15521248313
Email
hewei@sysucc.org.cn
First Name & Middle Initial & Last Name & Degree
Binkui Li

12. IPD Sharing Statement

Learn more about this trial

Bevacizumab in Combination With Sintilimab Versus Transcatheter Arterial Chemoembolization for the Treatment of Intermediate Stage Hepatocellular Carcinoma (Beyond Up-To-Seven Criteria)

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