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

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

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma; Bevacizumab; TACE; Adebrelimab; Transformation
• Intervention / Treatment: Drug: TACE with adebrelimab and bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 71
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jianbo Chen; Phone Number: 15605921022; Email: 274439002@qq.com

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China
      • Recruiting
      • The First Affiliated Hospital of Xiamen University
      • Contact: Jianbo Chen; Phone Number: 15605921022; Email: 274439002@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: 18 ~ 75, both male and female；
2. 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）；
3. Patients without previous systematic treatment and inoperable resection / radical ablation surgery, but who can tolerate TACE;
4. The CNLC stage is Ⅱa-Ⅲb stage;
5. The Child-Pugh grade of liver function is A grade or B grade (5-7 points);
6. The ECOG PS score is 0-1 points;
7. Expected survival period of 12 weeks;
8. 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;
9. 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；
10. 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;
11. The subjects volunteered to join the study and had good compliance with the follow-up.

Exclusion Criteria:

1. Pregnant or lactating women;
2. The pathology is clearly cholangiocytic carcinoma or mixed cell carcinoma;
3. Diffuse liver cancer;
4. 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);
5. Patients with consciousness disorders or unable to cooperate with the treatment, combined with patients with mental illness;
6. Patients who have participated in other clinical trials in the recent three months;
7. Previous history of other malignancies or have received targeted therapy and other PD-1 / PD-L1 inhibitor therapy;
8. 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;
9. Use of immunosuppressants or systemic hormone therapy within 14 days before enrollment to achieve immunosuppressive purposes (dose> 10mg / day prednisone or other efficacy hormones);
10. Liver function was graded as Child-Pugh C, which could not be improved by liver care treatment；
11. esophageal (gastric fundus) varices rupture and bleeding within 1 month before treatment；
12. 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);
13. A stubborn amount of ascites, pleural fluid, malignant fluid;
14. Active infection, especially the inflammation of the biliary tract system;
15. Severe functional failure of the liver, kidney, heart, lung, brain and other major organs;
16. Previously allergic to PD-1 / PD-L1 mAb / any component of the targeted drug or other similar trials;
17. Patients with hypertension who cannot be reduced to the normal range by antihypertensive medication (systolic blood pressure> 140 mmHg, diastolic blood pressure> 90 mmHg);
18. 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%;
19. Patients with positive urinary protein (urinary protein test of 2 + or above, or 24-hour urinary protein quantification of> 1.0g);
20. Failure to swallow tablets, malabsorption syndrome, or any condition affecting gastrointestinal absorption;
21. According to the discretion of the investigator, patients with other concomitant diseases that seriously endanger patient safety or affect the completion of the study;
22. Patients with radiotherapy, targeted therapy, and other contraindications to immunotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm	Drug: TACE with adebrelimab and bevacizumab; TACE treatment once; Adebrelimab: 20mg/kg, every 3 weeks (21 days); Bevacizumab; 15mg/kg, every 3 weeks (21 days);

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 2 years
Occurence of AE and SAE	Occurence of Adverse Event (AE) and Serious Adverse Event (SAE) （NCI CTCAE 5.0）	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Up to 2 years
Radical (R0) resection rate after conversion therapy	The cut margin had no residual cancer cells	Up to 2 years
percent conversion	The ates of conversion to operable patients in inoperable patients	Up to 2 years
Pathological complete response rate (pCR)	The rate of no remaining tumor cells in the excised tissue samples	Up to 2 years
Major pathological response rate (MPR)	The ratio of the tumor cells active in the removed tissue samples is less than 10%.	Up to 2 years
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.	Up to 2 years
Relapse-free survival time (RFS)	Time from date of cure surgery to time of recurrence or death	Up to 2 years
Overall survival（OS）	Defined as the time from the date of the first dose to the death of the subject from any cause.	Up to 2 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Xiamen University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Study Director: Feng Lin, Ningde Mindong Hospital; Principal Investigator: Jianbo Chen, The First Affiliated Hospital of Xiamen University; Principal Investigator: Feng Ye, The First Affiliated Hospital of Xiamen University; Study Director: congren Wang, Quanzhou First Hospital; Study Director: Qinghe Cai, Affiliated Hospital of Putian University; Study Director: Jiafei Chen, Putian First Hospital; Study Director: Yongzhong Wang, Sanming Second Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2023
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): November 15, 2026

Study Registration Dates

• First Submitted: July 25, 2023
• First Submitted That Met QC Criteria: July 25, 2023
• First Posted (Actual): August 1, 2023

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: 23-OBU-FJ-HCC-II-012

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No