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TACE Combined With Bevacizumab in HCC (BCLC-B) Beyond Up-To-Seven Criteria (B-TACE)

Primary Purpose

Hepatocellular Carcinoma by BCLC Stage

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Bevacizumab Biosimilar QL 1101
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 by BCLC Stage focused on measuring TACE, Bevacizumab Biosimilar, Hepatocellular carcinoma, Beyond up to seven criteria, Combination therapy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: The patient voluntarily joined the study and signed an informed consent form; ≥18 and ≤ 70 years old, both male and female; Clinically diagnosed or pathologically confirmed hepatocellular carcinoma, at least one measurable focus without local treatment (according to mRECIST requirements, the measurable focus spiral CT scan length ≥ 10 mm or enlargement Short diameter of lymph node ≥15 mm); Child-Pugh score ≤ 7 points; BCLC-B stage and multiple tumors beyond up-to-seven criteria; Newly diagnosed patients who have not received targeted therapy or immunotherapy in the past; ECOG score: 0~1; Expected survival period ≥ 12 weeks; The functions of vital organs meet the following requirements (no blood components, cell growth factors and other corrective treatment drugs are allowed within 14 days before the first administration): The absolute count of neutrophils≥1.5×109/L; Platelet ≥80×109/L; Hemoglobin ≥90 g/L; Serum albumin ≥28 g/L; Thyroid-stimulating hormone (TSH)≤1×ULN (if abnormal, the levels of FT3 and FT4 should be examined at the same time, if the levels of FT3 and FT4 are normal, they can be included in the group); Bilirubin≤1.5×ULN (within 7 days before the first administration); ALT and AST ≤3×ULN (within 7 days before the first dose); AKP≤ 2.5×ULN; Serum creatinine≤1.5×ULN; Non-surgical sterilization or female patients of childbearing age need to use a medically approved contraceptive method (such as an intrauterine device, contraceptive, or condom) during the study treatment period and within 3 months after the end of the study treatment period; Female patients of childbearing age who undergo surgical sterilization must be negative in serum or urine HCG within 72 hours before enrollment in the study; and must be non-lactating; for male patients whose partners are women of childbearing age, at the last time use effective methods for contraception within 3 months. Exclusion Criteria: The patient has any active autoimmune disease or a history of autoimmune disease; The patient is using immunosuppressive agents or systemic hormone therapy to achieve the purpose of immunosuppression (dose>10mg/day prednisone or other curative hormones), and continues to use it within 2 weeks before enrollment; The number of system treatment lines ≥ 2 lines; Severe allergic reaction to other monoclonal antibodies; Those with a known history of central nervous system metastasis or hepatic encephalopathy; Patients who have received liver transplantation in the past; Ascites with clinical symptoms, those who need puncture, drainage, or those who have received ascites drainage within the past 3 months, except those who have only a small amount of ascites on imaging but not accompanied by clinical symptoms; Suffer from high blood pressure and cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg); Uncontrolled cardiac clinical symptoms or diseases, such as: NYHA level 2 or higher heart failure, unstable angina pectoris, myocardial infarction occurred within 1 year, clinically significant supraventricular or ventricular arrhythmia requires treatment or intervention , QTc>450ms (male); QTc>470ms (female); Abnormal coagulation function (INR>2.0, PT>16s), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy, and allow the preventive use of low-dose aspirin and low molecular heparin; Significant clinically significant bleeding symptoms or clear bleeding tendency occurred within 3 months before randomization, such as pertussis/hemoptysis 2.5ml or more, gastrointestinal bleeding, esophageal and gastric varices with bleeding risk, hemorrhagic stomach Ulcer or vasculitis, etc., if the stool occult blood is positive at the baseline, it can be re-examined. If it is still positive after the re-examination, a gastroscopy is required. If the gastroscope shows severe esophageal and gastric varices, it cannot be included in the group (3 before the group) Except those who have undergone gastroscopy within a month or less to exclude such cases); Arterial/venous thrombosis events that occurred within 6 months before randomization, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; Known genetic or acquired bleeding and thrombotic tendency (such as hemophilia patients, coagulation dysfunction, thrombocytopenia, etc.); Urine routine test showed urine protein ≥ ++ and confirmed 24-hour urine protein content> 1.0 g; Patients who have previously received radiotherapy, chemotherapy, hormone therapy, and surgery, after the completion of the treatment (last medication) and less than 4 weeks before the study medication; molecular targeted therapy (including other oral targeted drugs used in clinical trials) is less than the first study medication <5 drug half-lives, or patients whose adverse events (except alopecia) caused by previous treatment have not recovered to ≤ CTCAE level 1; The patient has active infection, fever of unknown origin within 7 days before medication ≥38.5℃, or baseline white blood cell count >15×109/L; Patients with congenital or acquired immune deficiencies (such as HIV-infected persons); Patients with HBV DNA>2000 IU/ml (or 104 copies/ml), HCV RNA>103 copies/ml, HBsAg+ and anti-HCV antibody positive; The patient suffered from other malignant tumors in the past 3 years or at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ); Patients with bone metastases who received palliative radiotherapy within 4 weeks before participating in the study >5% of the bone marrow area; The patient has previously received other anti-PD-1 antibody therapy or other immunotherapy against PD-1/PD-L1, or has previously received apatinib therapy; Live vaccine may be vaccinated less than 4 weeks before study medication or may be administered during the study period; According to the judgment of the investigator, the patient has other factors that may affect the results of the study or cause the study to be terminated halfway, such as alcoholism, drug abuse, other serious diseases (including mental illness) that require combined treatment, and serious laboratory tests Abnormalities, accompanied by family or social factors, will affect the safety of patients.

Sites / Locations

  • Sun Yat-sen University Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

B-TACE

Arm Description

TACE Combined With Bevacizumab Biosimilar

Outcomes

Primary Outcome Measures

Objective response rate (ORR) by RECIST 1.1 and mRECIST
ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1 and mRECIST

Secondary Outcome Measures

Disease control rate (DCR)
DCR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) or stable disease (SD) at the time of data cutoff as assessed by RECIST 1.1 and mRECIST.
Duration of response (DOR) by RECIST 1.1 and mRECIST
DOR is defined as the time from the first documentation of CR or PR to the date of first documentation of disease progression or death (whichever occurs first) as assessed by RECIST 1.1 and mRECIST.
Progression-free survival (PFS) by RECIST 1.1 and mRECIST
assessed by RECIST 1.1 and mRECIST.
Overall survival rate (OSR)
OSR in 6- and 12-months.
Progression-free survival time (mPFS)
The progression-free survival time (mPFS) defined as the time from the first study dose date to the date of first documentation of disease progression as assessed by RECIS.
Median overall survival time (mOS)
ase (date of first study dose) until date of death from any cause. Participants who are lost to follow-up and the participants who are alive at the date of data cutoff will be censored at the date the participant was last known alive or the cut-off date, whichever comes earlier.

Full Information

First Posted
May 20, 2023
Last Updated
May 20, 2023
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT05883176
Brief Title
TACE Combined With Bevacizumab in HCC (BCLC-B) Beyond Up-To-Seven Criteria
Acronym
B-TACE
Official Title
TACE Combined With Bevacizumab in Patients With BCLC-B Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria: a Prospective Single-arm Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 1, 2023 (Anticipated)
Primary Completion Date
May 31, 2025 (Anticipated)
Study Completion Date
July 1, 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

5. Study Description

Brief Summary
The purpose of this study is to evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with anti-VEGF (Bevacizumab Biosimilar) in patients with BCLC-B stage hepatocellular carcinoma beyond up-to-seven criteria.
Detailed Description
This is a prospective, single-arm, phase II study to evaluate the efficacy and safety of TACE combined with anti-VEGF (Bevacizumab Biosimilar) in patients with BCLC-B stage hepatocellular carcinoma beyond up-to-seven criteria. Subjects who meet the admission criteria will be treated with Bevacizumab Biosimilar after TACE until disease progression, intolerable toxicity, death, patient withdrawal or the investigators determine that the drug must be discontinued. The primary outcome is the objective response rate (ORR). The secondary outcomes include the duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival rate (OSR) in 6- and 12-months, the median progression-free survival time (mPFS) and median overall survival time (mOS). This study also aims to assess the safety and adverse events of TACE combined with anti-VEGF (Bevacizumab Biosimilar) for HCC (BCLC-B stage) 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 by BCLC Stage
Keywords
TACE, Bevacizumab Biosimilar, Hepatocellular carcinoma, Beyond up to seven criteria, Combination therapy

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
B-TACE
Arm Type
Experimental
Arm Description
TACE Combined With Bevacizumab Biosimilar
Intervention Type
Drug
Intervention Name(s)
Bevacizumab Biosimilar QL 1101
Other Intervention Name(s)
TACE
Intervention Description
TACE + Bevacizumab (15mg/kg, intra-arterial infusion, Q3W) for 4 cycles, followed by maintenance therapy with Bevacizumab (15mg/kg, intravenously, Q3W) to a maximum total cycle of 18 unless any evidence of disease progression or unacceptable side effects.
Primary Outcome Measure Information:
Title
Objective response rate (ORR) by RECIST 1.1 and mRECIST
Description
ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1 and mRECIST
Time Frame
From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 2 years)
Secondary Outcome Measure Information:
Title
Disease control rate (DCR)
Description
DCR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) or stable disease (SD) at the time of data cutoff as assessed by RECIST 1.1 and mRECIST.
Time Frame
From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to 2 years)
Title
Duration of response (DOR) by RECIST 1.1 and mRECIST
Description
DOR is defined as the time from the first documentation of CR or PR to the date of first documentation of disease progression or death (whichever occurs first) as assessed by RECIST 1.1 and mRECIST.
Time Frame
From the first documentation of CR or PR to the first date of documentation of disease progression or death whichever occurs first (up to 2 years)
Title
Progression-free survival (PFS) by RECIST 1.1 and mRECIST
Description
assessed by RECIST 1.1 and mRECIST.
Time Frame
From date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurs first (up to 2 years)
Title
Overall survival rate (OSR)
Description
OSR in 6- and 12-months.
Time Frame
From date of first dose of study drug to the date of first documentation of death from any cause, whichever occurs first (up to 2 years)
Title
Progression-free survival time (mPFS)
Description
The progression-free survival time (mPFS) defined as the time from the first study dose date to the date of first documentation of disease progression as assessed by RECIS.
Time Frame
From date of first dose of study drug to the date of first documentation of death from any cause, whichever occurs first (up to 2 years)
Title
Median overall survival time (mOS)
Description
ase (date of first study dose) until date of death from any cause. Participants who are lost to follow-up and the participants who are alive at the date of data cutoff will be censored at the date the participant was last known alive or the cut-off date, whichever comes earlier.
Time Frame
From the start date of the Treatment Phase until date of death from any cause (up to 2 years)
Other Pre-specified Outcome Measures:
Title
Treatment-related adverse events
Description
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.
Time Frame
From the start date of the Treatment Phase until date of death from any cause (up to 2 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The patient voluntarily joined the study and signed an informed consent form; ≥18 and ≤ 70 years old, both male and female; Clinically diagnosed or pathologically confirmed hepatocellular carcinoma, at least one measurable focus without local treatment (according to mRECIST requirements, the measurable focus spiral CT scan length ≥ 10 mm or enlargement Short diameter of lymph node ≥15 mm); Child-Pugh score ≤ 7 points; BCLC-B stage and multiple tumors beyond up-to-seven criteria; Newly diagnosed patients who have not received targeted therapy or immunotherapy in the past; ECOG score: 0~1; Expected survival period ≥ 12 weeks; The functions of vital organs meet the following requirements (no blood components, cell growth factors and other corrective treatment drugs are allowed within 14 days before the first administration): The absolute count of neutrophils≥1.5×109/L; Platelet ≥80×109/L; Hemoglobin ≥90 g/L; Serum albumin ≥28 g/L; Thyroid-stimulating hormone (TSH)≤1×ULN (if abnormal, the levels of FT3 and FT4 should be examined at the same time, if the levels of FT3 and FT4 are normal, they can be included in the group); Bilirubin≤1.5×ULN (within 7 days before the first administration); ALT and AST ≤3×ULN (within 7 days before the first dose); AKP≤ 2.5×ULN; Serum creatinine≤1.5×ULN; Non-surgical sterilization or female patients of childbearing age need to use a medically approved contraceptive method (such as an intrauterine device, contraceptive, or condom) during the study treatment period and within 3 months after the end of the study treatment period; Female patients of childbearing age who undergo surgical sterilization must be negative in serum or urine HCG within 72 hours before enrollment in the study; and must be non-lactating; for male patients whose partners are women of childbearing age, at the last time use effective methods for contraception within 3 months. Exclusion Criteria: The patient has any active autoimmune disease or a history of autoimmune disease; The patient is using immunosuppressive agents or systemic hormone therapy to achieve the purpose of immunosuppression (dose>10mg/day prednisone or other curative hormones), and continues to use it within 2 weeks before enrollment; The number of system treatment lines ≥ 2 lines; Severe allergic reaction to other monoclonal antibodies; Those with a known history of central nervous system metastasis or hepatic encephalopathy; Patients who have received liver transplantation in the past; Ascites with clinical symptoms, those who need puncture, drainage, or those who have received ascites drainage within the past 3 months, except those who have only a small amount of ascites on imaging but not accompanied by clinical symptoms; Suffer from high blood pressure and cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg); Uncontrolled cardiac clinical symptoms or diseases, such as: NYHA level 2 or higher heart failure, unstable angina pectoris, myocardial infarction occurred within 1 year, clinically significant supraventricular or ventricular arrhythmia requires treatment or intervention , QTc>450ms (male); QTc>470ms (female); Abnormal coagulation function (INR>2.0, PT>16s), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy, and allow the preventive use of low-dose aspirin and low molecular heparin; Significant clinically significant bleeding symptoms or clear bleeding tendency occurred within 3 months before randomization, such as pertussis/hemoptysis 2.5ml or more, gastrointestinal bleeding, esophageal and gastric varices with bleeding risk, hemorrhagic stomach Ulcer or vasculitis, etc., if the stool occult blood is positive at the baseline, it can be re-examined. If it is still positive after the re-examination, a gastroscopy is required. If the gastroscope shows severe esophageal and gastric varices, it cannot be included in the group (3 before the group) Except those who have undergone gastroscopy within a month or less to exclude such cases); Arterial/venous thrombosis events that occurred within 6 months before randomization, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; Known genetic or acquired bleeding and thrombotic tendency (such as hemophilia patients, coagulation dysfunction, thrombocytopenia, etc.); Urine routine test showed urine protein ≥ ++ and confirmed 24-hour urine protein content> 1.0 g; Patients who have previously received radiotherapy, chemotherapy, hormone therapy, and surgery, after the completion of the treatment (last medication) and less than 4 weeks before the study medication; molecular targeted therapy (including other oral targeted drugs used in clinical trials) is less than the first study medication <5 drug half-lives, or patients whose adverse events (except alopecia) caused by previous treatment have not recovered to ≤ CTCAE level 1; The patient has active infection, fever of unknown origin within 7 days before medication ≥38.5℃, or baseline white blood cell count >15×109/L; Patients with congenital or acquired immune deficiencies (such as HIV-infected persons); Patients with HBV DNA>2000 IU/ml (or 104 copies/ml), HCV RNA>103 copies/ml, HBsAg+ and anti-HCV antibody positive; The patient suffered from other malignant tumors in the past 3 years or at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ); Patients with bone metastases who received palliative radiotherapy within 4 weeks before participating in the study >5% of the bone marrow area; The patient has previously received other anti-PD-1 antibody therapy or other immunotherapy against PD-1/PD-L1, or has previously received apatinib therapy; Live vaccine may be vaccinated less than 4 weeks before study medication or may be administered during the study period; According to the judgment of the investigator, the patient has other factors that may affect the results of the study or cause the study to be terminated halfway, such as alcoholism, drug abuse, other serious diseases (including mental illness) that require combined treatment, and serious laboratory tests Abnormalities, accompanied by family or social factors, will affect the safety of patients.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fei Gao, Ph.D., M.D.
Phone
86-13760869828
Email
gaof@sysucc.org.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Han Qi, M.D.
Phone
86-15920316143
Email
Qih@sysucc.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fei Gao, Ph.D., M.D.
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

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TACE Combined With Bevacizumab in HCC (BCLC-B) Beyond Up-To-Seven Criteria

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