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Efficacy and Safety of SCAI of Bevacizumab Combined With IC of Tislelizumab in the Treatment of Recurrent Glioblastoma.

Primary Purpose

Glioblastoma

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Tislelizumab and Bevacizumab
Sponsored by
Second Affiliated Hospital of Nanchang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma

Eligibility Criteria

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

Inclusion Criteria: 1, 18 ≤ age ≤ 75 years. 2. Recurrent glioblastoma who failed first-line therapy, with no more than 3 prior episodes of disease progression and at least one confirmed and evaluable lesion. 3. ECOG score 0-2 points, expected survival time ≥ 3 months; 4. Stable neurological symptoms for more than 7 days; 5. If the previous surgical resection interval is at least 4 weeks, after receiving chemotherapy for 3 weeks, after receiving radiotherapy including whole brain radiotherapy, stereotactic radiotherapy and other radiotherapy for 3 months, if receiving other intrathecal treatment drugs washout period of 7 days. 6. Neutrophil count ≥ 1.5 × 10 ^ 9/L, hemoglobin ≥ 80 g/L, platelets ≥ 75 × 10 ^ 9/L. 7. Prothrombin time/international normalized ratio and partial thromboplastin time ≤ 1.5 × upper limit of normal; 8. Total bilirubin ≤ 1.5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ×ULN, albumin ≥ 30 g/L, creatinine ≤ 2 × ULN, calculated creatinine clearance ≥ 50 mL/min, 24-hour urine creatinine clearance ≥ 50 mL/min; 9. subjects should agree to use adequate contraception from the first dose until 3 months after the last dose. Exclusion Criteria: 1. Pregnant or lactating women. 2. Active infection requiring intravenous antibiotics requiring therapeutic anticoagulation with warfarin. 3. History of allergy to monoclonal antibodies; 4. Use of non-tumor vaccines containing live viruses to prevent infectious diseases within 12 weeks before the study drug; 5. Subjects with serious medical, neurological or psychiatric disorders and judged to be unable to fully comply with study treatment or assessments; 6. Active infectious diseases within 7 days before starting the study drug; 7. Severe liver dysfunction (persistent grade 3 or greater liver adverse events) or known active chronic hepatitis, human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) test positive; 8. Patients with active autoimmune diseases requiring systemic treatment (i.e., the use of corticosteroids or immunosuppressive agents), except replacement therapy (e.g., thyroxine, insulin or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency), allowing inhalation or local steroids and adrenal replacement dose > 10 mg daily prednisone equivalent, requiring long-term systemic corticosteroid therapy (> 10 mg prednisone or equivalent per day) or any other immunosuppressive therapy (including anti-TNF-a therapy); 9. Investigate the allergic history of drug ingredients; 10. Inadequate control of hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg (using antihypertensive drugs); 11. Any past history of hypertensive crisis or hypertensive encephalopathy; 12. New York Heart Association (NYHA) Class II or greater congestive heart failure; 13. History of myocardial infarction or unstable angina within 6 months prior to enrollment; 14. History of stroke or transient ischemic attack within 6 months prior to enrollment; 15. Severe vascular diseases (such as aortic aneurysm, aortic dissection); 16. Symptomatic peripheral vascular disease. 17. Evidence of bleeding diathesis or coagulopathy. 18. Major surgery, open biopsy or severe traumatic injury within 28 days prior to study enrollment, or major surgery is expected to be required during the course of the study. 19. Core biopsy or other minor surgical procedures, excluding placement of vascular access devices, within 7 days prior to study enrollment. 20. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry; 21. Severe, non-healing wounds, ulcers or fractures. 22. Urine protein to creatinine ratio ≥ 1.0 or urine protein ≥ 2 +. 23. Subjects with high intracranial pressure who are not suitable for lumbar puncture, and the researchers believe that they are not suitable for inclusion in the study.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Bevacizumab arterial infusion combined with Tislelizumab intrathecal injection

    Arm Description

    This is a prospective, interventional, multicenter Phase 2 trial for the treatment of patients with recurrent GBM who will receive Bevacizumab arterial infusion combined with Tislelizumab intrathecal injection. The study consists of two parts: the "arterial infusion part" in part 1, where each subject will receive 15 mg/Kg of Bevacizumab by cerebral arterial infusion over 15 minutes at a fixed time (d0, d30, d60); the infusion of 20% mannitol 12.5 ml over 120 seconds prior to the infusion of Bevacizumab; and the "intrathecal injection part" in part 2, where the subject will receive a fixed dose of intrathecal PD1 therapy (Tislelizumab 20 mg, d1, Q3W) intrathecal injection every 3 weeks for 6 cycles.

    Outcomes

    Primary Outcome Measures

    Progression-Free Survival
    PFS was defined as the time from random assignment until objective tumor progression (independent image committee assessment) or death (any cause)

    Secondary Outcome Measures

    Objective Response Rate
    ORR is defined as the percentage of patients with a best overall response of CR or PR relative to the appropriate analysis set.
    Overall Survival
    OS was defined as the time from random assignment until death (any cause) or censored at the last date of known survival.
    Duration of Response
    Time from the patient 's first assessment of clinical response to the first assessment of disease progression or death from any cause.
    Safety and Tolerability
    The safety endpoints will be assessed by a review of adverse events and serious adverse events according to CTCAE up to 10 approximately months after last dose

    Full Information

    First Posted
    March 21, 2023
    Last Updated
    April 12, 2023
    Sponsor
    Second Affiliated Hospital of Nanchang University
    Collaborators
    Zhejiang University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05811793
    Brief Title
    Efficacy and Safety of SCAI of Bevacizumab Combined With IC of Tislelizumab in the Treatment of Recurrent Glioblastoma.
    Official Title
    Efficacy and Safety of Superselective Cerebral Arterial Infusion of Bevacizumab Combined With Intrathecal Injection of Tislelizumab in the Treatment of Recurrent Glioblastoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    April 15, 2023 (Anticipated)
    Primary Completion Date
    December 2024 (Anticipated)
    Study Completion Date
    December 30, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Second Affiliated Hospital of Nanchang University
    Collaborators
    Zhejiang 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
    To investigate the efficacy, safety and tolerability of superselective cerebral arterial infusion of Bevacizumab combined with intrathecal injection of Tislelizumab in the treatment of recurrent glioblastoma
    Detailed Description
    Glioblastoma multiforme (GBM) is a highly malignant intracranial tumor with a median survival of only about 15-17 months after standard treatment. Patients with GBM often experience disease recurrence, and once recurrence occurs, treatment options are very limited, with a median overall survival of only about 6 months. Results of a phase II clinical trial of nivolumab combined with standard or reduced-dose bevacizumab iv therapy for recurrent GBM showed that the median PFS for the two groups was 5.6 months vs. 4.6 months, respectively. The aim of this study is to improve the outcome of recurrent GBM patients by changing the route of administration of the two drugs, such as delivering Bevacizumab via intra-arterial infusion and administering PD-1 monoclonal antibodies via intrathecal injection.

    6. Conditions and Keywords

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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    36 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Bevacizumab arterial infusion combined with Tislelizumab intrathecal injection
    Arm Type
    Experimental
    Arm Description
    This is a prospective, interventional, multicenter Phase 2 trial for the treatment of patients with recurrent GBM who will receive Bevacizumab arterial infusion combined with Tislelizumab intrathecal injection. The study consists of two parts: the "arterial infusion part" in part 1, where each subject will receive 15 mg/Kg of Bevacizumab by cerebral arterial infusion over 15 minutes at a fixed time (d0, d30, d60); the infusion of 20% mannitol 12.5 ml over 120 seconds prior to the infusion of Bevacizumab; and the "intrathecal injection part" in part 2, where the subject will receive a fixed dose of intrathecal PD1 therapy (Tislelizumab 20 mg, d1, Q3W) intrathecal injection every 3 weeks for 6 cycles.
    Intervention Type
    Drug
    Intervention Name(s)
    Tislelizumab and Bevacizumab
    Intervention Description
    Tislelizumab is a drug material authorized for marketing in China. Tislelizumab will be administered off-label in this study. Subjects with recurrent GBM will receive intrathecal tislelizumab every 3 weeks for six times. Intrathecal administration of Bevacizumab will be performed via Ommaya reservoir or intraventricular catheter.
    Primary Outcome Measure Information:
    Title
    Progression-Free Survival
    Description
    PFS was defined as the time from random assignment until objective tumor progression (independent image committee assessment) or death (any cause)
    Time Frame
    Up to 10 approximately months
    Secondary Outcome Measure Information:
    Title
    Objective Response Rate
    Description
    ORR is defined as the percentage of patients with a best overall response of CR or PR relative to the appropriate analysis set.
    Time Frame
    Up to 10 approximately months
    Title
    Overall Survival
    Description
    OS was defined as the time from random assignment until death (any cause) or censored at the last date of known survival.
    Time Frame
    Up to 10 approximately months
    Title
    Duration of Response
    Description
    Time from the patient 's first assessment of clinical response to the first assessment of disease progression or death from any cause.
    Time Frame
    Up to 10 approximately months
    Title
    Safety and Tolerability
    Description
    The safety endpoints will be assessed by a review of adverse events and serious adverse events according to CTCAE up to 10 approximately months after last dose
    Time Frame
    Up to 10 approximately months

    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: 1, 18 ≤ age ≤ 75 years. 2. Recurrent glioblastoma who failed first-line therapy, with no more than 3 prior episodes of disease progression and at least one confirmed and evaluable lesion. 3. ECOG score 0-2 points, expected survival time ≥ 3 months; 4. Stable neurological symptoms for more than 7 days; 5. If the previous surgical resection interval is at least 4 weeks, after receiving chemotherapy for 3 weeks, after receiving radiotherapy including whole brain radiotherapy, stereotactic radiotherapy and other radiotherapy for 3 months, if receiving other intrathecal treatment drugs washout period of 7 days. 6. Neutrophil count ≥ 1.5 × 10 ^ 9/L, hemoglobin ≥ 80 g/L, platelets ≥ 75 × 10 ^ 9/L. 7. Prothrombin time/international normalized ratio and partial thromboplastin time ≤ 1.5 × upper limit of normal; 8. Total bilirubin ≤ 1.5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ×ULN, albumin ≥ 30 g/L, creatinine ≤ 2 × ULN, calculated creatinine clearance ≥ 50 mL/min, 24-hour urine creatinine clearance ≥ 50 mL/min; 9. subjects should agree to use adequate contraception from the first dose until 3 months after the last dose. Exclusion Criteria: 1. Pregnant or lactating women. 2. Active infection requiring intravenous antibiotics requiring therapeutic anticoagulation with warfarin. 3. History of allergy to monoclonal antibodies; 4. Use of non-tumor vaccines containing live viruses to prevent infectious diseases within 12 weeks before the study drug; 5. Subjects with serious medical, neurological or psychiatric disorders and judged to be unable to fully comply with study treatment or assessments; 6. Active infectious diseases within 7 days before starting the study drug; 7. Severe liver dysfunction (persistent grade 3 or greater liver adverse events) or known active chronic hepatitis, human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) test positive; 8. Patients with active autoimmune diseases requiring systemic treatment (i.e., the use of corticosteroids or immunosuppressive agents), except replacement therapy (e.g., thyroxine, insulin or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency), allowing inhalation or local steroids and adrenal replacement dose > 10 mg daily prednisone equivalent, requiring long-term systemic corticosteroid therapy (> 10 mg prednisone or equivalent per day) or any other immunosuppressive therapy (including anti-TNF-a therapy); 9. Investigate the allergic history of drug ingredients; 10. Inadequate control of hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg (using antihypertensive drugs); 11. Any past history of hypertensive crisis or hypertensive encephalopathy; 12. New York Heart Association (NYHA) Class II or greater congestive heart failure; 13. History of myocardial infarction or unstable angina within 6 months prior to enrollment; 14. History of stroke or transient ischemic attack within 6 months prior to enrollment; 15. Severe vascular diseases (such as aortic aneurysm, aortic dissection); 16. Symptomatic peripheral vascular disease. 17. Evidence of bleeding diathesis or coagulopathy. 18. Major surgery, open biopsy or severe traumatic injury within 28 days prior to study enrollment, or major surgery is expected to be required during the course of the study. 19. Core biopsy or other minor surgical procedures, excluding placement of vascular access devices, within 7 days prior to study enrollment. 20. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry; 21. Severe, non-healing wounds, ulcers or fractures. 22. Urine protein to creatinine ratio ≥ 1.0 or urine protein ≥ 2 +. 23. Subjects with high intracranial pressure who are not suitable for lumbar puncture, and the researchers believe that they are not suitable for inclusion in the study.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Xingen Zhu, Dr.
    Phone
    18679136068
    Email
    zxg2008vip@163.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Xingen Zhu, Dr.
    Organizational Affiliation
    Second Affiliated Hospital of Nanchang University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Efficacy and Safety of SCAI of Bevacizumab Combined With IC of Tislelizumab in the Treatment of Recurrent Glioblastoma.

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