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

TACE Combined With Bevacizumab in Patients With BCLC-B Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria: a Prospective Single-arm Phase II Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma by BCLC Stage
• Intervention / Treatment: Drug: Bevacizumab Biosimilar QL 1101

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.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fei Gao, Ph.D., M.D.; Phone Number: 86-13760869828; Email: gaof@sysucc.org.cn
• Study Contact Backup: Name: Han Qi, M.D.; Phone Number: 86-15920316143; Email: Qih@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The patient voluntarily joined the study and signed an informed consent form;
2. ≥18 and ≤ 70 years old, both male and female;
3. 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);
4. Child-Pugh score ≤ 7 points;
5. BCLC-B stage and multiple tumors beyond up-to-seven criteria;
6. Newly diagnosed patients who have not received targeted therapy or immunotherapy in the past;
7. ECOG score: 0～1;
8. Expected survival period ≥ 12 weeks;
9. 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):
10. 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;
11. 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:

1. The patient has any active autoimmune disease or a history of autoimmune disease;
2. 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;
3. The number of system treatment lines ≥ 2 lines;
4. Severe allergic reaction to other monoclonal antibodies;
5. Those with a known history of central nervous system metastasis or hepatic encephalopathy;
6. Patients who have received liver transplantation in the past;
7. 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;
8. Suffer from high blood pressure and cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
9. 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);
10. 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;
11. 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);
12. 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;
13. 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;
14. 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;
15. 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);
16. Patients with HBV DNA>2000 IU/ml (or 104 copies/ml), HCV RNA>103 copies/ml, HBsAg+ and anti-HCV antibody positive;
17. 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);
18. Patients with bone metastases who received palliative radiotherapy within 4 weeks before participating in the study >5% of the bone marrow area;
19. 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;
20. Live vaccine may be vaccinated less than 4 weeks before study medication or may be administered during the study period;
21. 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
22. Abnormalities, accompanied by family or social factors, will affect the safety of patients.

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: B-TACE; TACE Combined With Bevacizumab Biosimilar	Drug: Bevacizumab Biosimilar QL 1101; 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.; Other Names: TACE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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 Measures

Outcome Measure	Measure Description	Time Frame
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.	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)
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.	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)
Progression-free survival (PFS) by RECIST 1.1 and mRECIST	assessed by RECIST 1.1 and mRECIST.	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)
Overall survival rate (OSR)	OSR in 6- and 12-months.	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)
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.	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)
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.	From the start date of the Treatment Phase until date of death from any cause (up to 2 years)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-related adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.	From the start date of the Treatment Phase until date of death from any cause (up to 2 years)

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Fei Gao, Ph.D., M.D., Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2023
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: May 20, 2023
• First Submitted That Met QC Criteria: May 20, 2023
• First Posted (Actual): May 31, 2023

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 20, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Hepatocellular carcinoma; TACE; Combination therapy; Bevacizumab Biosimilar; Beyond up to seven criteria
• 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: B-TACE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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