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Single Arm, Prospective, Multicenter Clinical Study of TACE With Adebrelimab and Bevacizumab for Unresectable Hepatocellular Carcinoma

Primary Purpose

Adebrelimab, Hepatocellular Carcinoma, Transformation

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
TACE with adebrelimab and bevacizumab
Sponsored by
The First Affiliated Hospital of Xiamen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adebrelimab

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age: 18 ~ 75, both male and female; Strictly comply with the primary liver cancer diagnosis and treatment standard (2022 edition) clinical diagnosis criteria or primary hepatocellular carcinoma diagnosed by pathological histology or cytology examination, and at least one measurable lesions (according to the RECIST1.1 standard, the spiral CT scan of 10mm or short diameter of 15mm); Patients without previous systematic treatment and inoperable resection / radical ablation surgery, but who can tolerate TACE; The CNLC stage is Ⅱa-Ⅲb stage; The Child-Pugh grade of liver function is A grade or B grade (5-7 points); The ECOG PS score is 0-1 points; Expected survival period of 12 weeks; If the patient has active hepatitis B virus (HBV) infection: HBV-deoxyribonucleic acid (DNA) must be <2000 IU / mL (if the study site has only copy / mL testing units, Must be <12500 copy / mL), And received at least 14 days before initiating anti-HBV treatment (according to local standard therapy, e. g. entecavir) and willing to receive antiviral treatment throughout the study; hepatitis C virus (HCV) ribonucleic acid (RNA) positive patients must receive antiviral treatment according to local standard treatment guidelines and liver function within grade CTCAE 1 elevation; Main organs function are normal and meet the following criteria: (1) The blood routine examination standards should be met with: (no blood transfusion within 14 days) A. Hemoglobin (HB), 90g / L, B. White blood cell count (WBC) 3109 / L C. Absolute neutrophil count (ANC) 1.5109 / L, D. Platelet (PLT) 80109 / L;(2) Biochemical examination shall meet the following standards: A. Bilirubin (BIL) <1.5 times the upper limit of normal value (ULN); B. Glutamic gamma aminotransferase (ALT) and glutamate aminotransferase AST <5 ULN; C. Serum creatinine (Cr)≤1.5ULN; Women of childbearing age must have negative pregnancy test (serum) or urine HCG within 7 days before enrollment and are willing to use appropriate contraception during treatment and 24 weeks after the last administration of test drug; for men, surgical sterilization or agree to use appropriate contraception during and 24 weeks after the last administration of trial drug; The subjects volunteered to join the study and had good compliance with the follow-up. Exclusion Criteria: Pregnant or lactating women; The pathology is clearly cholangiocytic carcinoma or mixed cell carcinoma; Diffuse liver cancer; Patients with autoimmune diseases, organ / hematopoietic stem cell transplantation or other malignant tumors (except for cured basal skin cell carcinoma and cervix carcinoma in situ); Patients with consciousness disorders or unable to cooperate with the treatment, combined with patients with mental illness; Patients who have participated in other clinical trials in the recent three months; Previous history of other malignancies or have received targeted therapy and other PD-1 / PD-L1 inhibitor therapy; Received major surgery or chemotherapy or other systemic therapy for target lesions (including not limited to radiation therapy, ablation therapy, etc.) within 1 month prior to enrollment; Use of immunosuppressants or systemic hormone therapy within 14 days before enrollment to achieve immunosuppressive purposes (dose> 10mg / day prednisone or other efficacy hormones); Liver function was graded as Child-Pugh C, which could not be improved by liver care treatment; esophageal (gastric fundus) varices rupture and bleeding within 1 month before treatment; Uncorrectable coagulopathy and severe blood abnormalities, with severe bleeding tendency. Platelet count <50109 / L and severe coagulation abnormalities against surgery (anticoagulation therapy and / or anticoagulant therapy should be stopped for more than 1 week before radiation therapy); A stubborn amount of ascites, pleural fluid, malignant fluid; Active infection, especially the inflammation of the biliary tract system; Severe functional failure of the liver, kidney, heart, lung, brain and other major organs; Previously allergic to PD-1 / PD-L1 mAb / any component of the targeted drug or other similar trials; Patients with hypertension who cannot be reduced to the normal range by antihypertensive medication (systolic blood pressure> 140 mmHg, diastolic blood pressure> 90 mmHg); Previous severe cardiovascular disease, including but not limited to the following diseases: myocardial ischemia or myocardial infarction, poorly controlled arrhythmia (including 450 ms in QTc men and 470 ms in women); cardiac dysfunction by NYHA, or cardiac ultrasound indicating left ventricular ejection fraction (LVEF) <50%; Patients with positive urinary protein (urinary protein test of 2 + or above, or 24-hour urinary protein quantification of> 1.0g); Failure to swallow tablets, malabsorption syndrome, or any condition affecting gastrointestinal absorption; According to the discretion of the investigator, patients with other concomitant diseases that seriously endanger patient safety or affect the completion of the study; Patients with radiotherapy, targeted therapy, and other contraindications to immunotherapy.

Sites / Locations

  • The First Affiliated Hospital of Xiamen University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single arm

Arm Description

Outcomes

Primary Outcome Measures

Objective response rate(ORR)
Refers to the proportion of all subjects with the best overall response (BOR) as complete remission (CR) or partial remission (PR) according to mRECIST 1.1 criteria.
Occurence of AE and SAE
Occurence of Adverse Event (AE) and Serious Adverse Event (SAE) (NCI CTCAE 5.0)

Secondary Outcome Measures

Radical (R0) resection rate after conversion therapy
The cut margin had no residual cancer cells
percent conversion
The ates of conversion to operable patients in inoperable patients
Pathological complete response rate (pCR)
The rate of no remaining tumor cells in the excised tissue samples
Major pathological response rate (MPR)
The ratio of the tumor cells active in the removed tissue samples is less than 10%.
Progression-free survival (PFS)
PFS was defined as the subject's date from the date of the first dose to the date of the first documented tumor progression (as assessed by mRECIST criteria, with or without continuation of treatment) or the date of death from any cause, whichever occurred first.
Disease control rate(DCR)
Refers to the proportion of all subjects with the best overall response (BOR) according to mRECIST criteria as complete remission (CR), partial remission (PR) and stable disease (SD).
Relapse-free survival time (RFS)
Time from date of cure surgery to time of recurrence or death
Overall survival(OS)
Defined as the time from the date of the first dose to the death of the subject from any cause.

Full Information

First Posted
July 25, 2023
Last Updated
July 25, 2023
Sponsor
The First Affiliated Hospital of Xiamen University
Collaborators
Jiangsu HengRui Medicine Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05970666
Brief Title
Single Arm, Prospective, Multicenter Clinical Study of TACE With Adebrelimab and Bevacizumab for Unresectable Hepatocellular Carcinoma
Official Title
Single Arm, Prospective, Multicenter Clinical Study of TACE With Adebrelimab and Bevacizumab for Unresectable Hepatocellular Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 1, 2023 (Anticipated)
Primary Completion Date
August 1, 2026 (Anticipated)
Study Completion Date
August 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital of Xiamen University
Collaborators
Jiangsu HengRui Medicine Co., Ltd.

4. Oversight

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

5. Study Description

Brief Summary
To evaluate the efficacy and safety of TACE combined with adebrelimab and bevacizumab transformation in unresectable hepatocellular carcinoma

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adebrelimab, Hepatocellular Carcinoma, Transformation, Bevacizumab, TACE

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
71 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single arm
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
TACE with adebrelimab and bevacizumab
Intervention Description
TACE treatment once; Adebrelimab: 20mg/kg, every 3 weeks (21 days); Bevacizumab; 15mg/kg, every 3 weeks (21 days);
Primary Outcome Measure Information:
Title
Objective response rate(ORR)
Description
Refers to the proportion of all subjects with the best overall response (BOR) as complete remission (CR) or partial remission (PR) according to mRECIST 1.1 criteria.
Time Frame
Up to 2 years
Title
Occurence of AE and SAE
Description
Occurence of Adverse Event (AE) and Serious Adverse Event (SAE) (NCI CTCAE 5.0)
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Radical (R0) resection rate after conversion therapy
Description
The cut margin had no residual cancer cells
Time Frame
Up to 2 years
Title
percent conversion
Description
The ates of conversion to operable patients in inoperable patients
Time Frame
Up to 2 years
Title
Pathological complete response rate (pCR)
Description
The rate of no remaining tumor cells in the excised tissue samples
Time Frame
Up to 2 years
Title
Major pathological response rate (MPR)
Description
The ratio of the tumor cells active in the removed tissue samples is less than 10%.
Time Frame
Up to 2 years
Title
Progression-free survival (PFS)
Description
PFS was defined as the subject's date from the date of the first dose to the date of the first documented tumor progression (as assessed by mRECIST criteria, with or without continuation of treatment) or the date of death from any cause, whichever occurred first.
Time Frame
Up to 2 years
Title
Disease control rate(DCR)
Description
Refers to the proportion of all subjects with the best overall response (BOR) according to mRECIST criteria as complete remission (CR), partial remission (PR) and stable disease (SD).
Time Frame
Up to 2 years
Title
Relapse-free survival time (RFS)
Description
Time from date of cure surgery to time of recurrence or death
Time Frame
Up to 2 years
Title
Overall survival(OS)
Description
Defined as the time from the date of the first dose to the death of the subject from any cause.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age: 18 ~ 75, both male and female; Strictly comply with the primary liver cancer diagnosis and treatment standard (2022 edition) clinical diagnosis criteria or primary hepatocellular carcinoma diagnosed by pathological histology or cytology examination, and at least one measurable lesions (according to the RECIST1.1 standard, the spiral CT scan of 10mm or short diameter of 15mm); Patients without previous systematic treatment and inoperable resection / radical ablation surgery, but who can tolerate TACE; The CNLC stage is Ⅱa-Ⅲb stage; The Child-Pugh grade of liver function is A grade or B grade (5-7 points); The ECOG PS score is 0-1 points; Expected survival period of 12 weeks; If the patient has active hepatitis B virus (HBV) infection: HBV-deoxyribonucleic acid (DNA) must be <2000 IU / mL (if the study site has only copy / mL testing units, Must be <12500 copy / mL), And received at least 14 days before initiating anti-HBV treatment (according to local standard therapy, e. g. entecavir) and willing to receive antiviral treatment throughout the study; hepatitis C virus (HCV) ribonucleic acid (RNA) positive patients must receive antiviral treatment according to local standard treatment guidelines and liver function within grade CTCAE 1 elevation; Main organs function are normal and meet the following criteria: (1) The blood routine examination standards should be met with: (no blood transfusion within 14 days) A. Hemoglobin (HB), 90g / L, B. White blood cell count (WBC) 3109 / L C. Absolute neutrophil count (ANC) 1.5109 / L, D. Platelet (PLT) 80109 / L;(2) Biochemical examination shall meet the following standards: A. Bilirubin (BIL) <1.5 times the upper limit of normal value (ULN); B. Glutamic gamma aminotransferase (ALT) and glutamate aminotransferase AST <5 ULN; C. Serum creatinine (Cr)≤1.5ULN; Women of childbearing age must have negative pregnancy test (serum) or urine HCG within 7 days before enrollment and are willing to use appropriate contraception during treatment and 24 weeks after the last administration of test drug; for men, surgical sterilization or agree to use appropriate contraception during and 24 weeks after the last administration of trial drug; The subjects volunteered to join the study and had good compliance with the follow-up. Exclusion Criteria: Pregnant or lactating women; The pathology is clearly cholangiocytic carcinoma or mixed cell carcinoma; Diffuse liver cancer; Patients with autoimmune diseases, organ / hematopoietic stem cell transplantation or other malignant tumors (except for cured basal skin cell carcinoma and cervix carcinoma in situ); Patients with consciousness disorders or unable to cooperate with the treatment, combined with patients with mental illness; Patients who have participated in other clinical trials in the recent three months; Previous history of other malignancies or have received targeted therapy and other PD-1 / PD-L1 inhibitor therapy; Received major surgery or chemotherapy or other systemic therapy for target lesions (including not limited to radiation therapy, ablation therapy, etc.) within 1 month prior to enrollment; Use of immunosuppressants or systemic hormone therapy within 14 days before enrollment to achieve immunosuppressive purposes (dose> 10mg / day prednisone or other efficacy hormones); Liver function was graded as Child-Pugh C, which could not be improved by liver care treatment; esophageal (gastric fundus) varices rupture and bleeding within 1 month before treatment; Uncorrectable coagulopathy and severe blood abnormalities, with severe bleeding tendency. Platelet count <50109 / L and severe coagulation abnormalities against surgery (anticoagulation therapy and / or anticoagulant therapy should be stopped for more than 1 week before radiation therapy); A stubborn amount of ascites, pleural fluid, malignant fluid; Active infection, especially the inflammation of the biliary tract system; Severe functional failure of the liver, kidney, heart, lung, brain and other major organs; Previously allergic to PD-1 / PD-L1 mAb / any component of the targeted drug or other similar trials; Patients with hypertension who cannot be reduced to the normal range by antihypertensive medication (systolic blood pressure> 140 mmHg, diastolic blood pressure> 90 mmHg); Previous severe cardiovascular disease, including but not limited to the following diseases: myocardial ischemia or myocardial infarction, poorly controlled arrhythmia (including 450 ms in QTc men and 470 ms in women); cardiac dysfunction by NYHA, or cardiac ultrasound indicating left ventricular ejection fraction (LVEF) <50%; Patients with positive urinary protein (urinary protein test of 2 + or above, or 24-hour urinary protein quantification of> 1.0g); Failure to swallow tablets, malabsorption syndrome, or any condition affecting gastrointestinal absorption; According to the discretion of the investigator, patients with other concomitant diseases that seriously endanger patient safety or affect the completion of the study; Patients with radiotherapy, targeted therapy, and other contraindications to immunotherapy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianbo Chen
Phone
15605921022
Email
274439002@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jianbo Chen
Organizational Affiliation
The First Affiliated Hospital of Xiamen University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Feng Ye
Organizational Affiliation
The First Affiliated Hospital of Xiamen University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
congren Wang
Organizational Affiliation
Quanzhou First Hospital
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Qinghe Cai
Organizational Affiliation
Affiliated Hospital of Putian University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Jiafei Chen
Organizational Affiliation
Putian First Hospital
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Yongzhong Wang
Organizational Affiliation
Sanming Second Hospital
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Feng Lin
Organizational Affiliation
Ningde Mindong Hospital
Official's Role
Study Director
Facility Information:
Facility Name
The First Affiliated Hospital of Xiamen University
City
Xiamen
State/Province
Fujian
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianbo Chen
Phone
15605921022
Email
274439002@qq.com

12. IPD Sharing Statement

Learn more about this trial

Single Arm, Prospective, Multicenter Clinical Study of TACE With Adebrelimab and Bevacizumab for Unresectable Hepatocellular Carcinoma

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