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

NCT05811793 | Unknown

• 1 other identifier: IIT-I-2023-016
• Study Type: interventional
• Target: 36
• Locations: 0 countries
• Sites: N/A

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

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

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

  Up to 10 approximately months

Secondary Outcomes (4)

• Objective Response Rate

  Up to 10 approximately months

• Overall Survival

  Up to 10 approximately months

• Duration of Response

  Up to 10 approximately months

• Safety and Tolerability

  Up to 10 approximately months

Study Arms (1)

Bevacizumab arterial infusion combined with Tislelizumab intrathecal injection

EXPERIMENTAL

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.

Drug: Tislelizumab and Bevacizumab

Interventions

Tislelizumab and Bevacizumab DRUG

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.

Bevacizumab arterial infusion combined with Tislelizumab intrathecal injection

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• , 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.
• \. 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.
• \. Neutrophil count ≥ 1.5 × 10 \^ 9/L, hemoglobin ≥ 80 g/L, platelets ≥ 75 × 10 \^ 9/L.
• \. 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.

You may not qualify if:

• \. Pregnant or lactating women. 2. Active infection requiring intravenous antibiotics requiring therapeutic anticoagulation with warfarin.
• \. 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.
• \. Core biopsy or other minor surgical procedures, excluding placement of vascular access devices, within 7 days prior to study enrollment.

Sponsors & Collaborators

• Second Affiliated Hospital of Nanchang University: lead
• Zhejiang University: collaborator

MeSH Terms

Conditions

Glioblastoma

Interventions

tislelizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Xingen Zhu, Dr.

  Second Affiliated Hospital of Nanchang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xingen Zhu, Dr.

CONTACT

18679136068; zxg2008vip@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2023
• First Posted: April 13, 2023
• Study Start: April 15, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 30, 2025
• Last Updated: April 13, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share