Repeated Super-Selective Intraarterial Cerebral Infusion of Bevacizumab (Avastin) for Treatment of Newly Diagnosed GBM

Phase 1

Completed

• Conditions: Glioblastoma Multiforme; Brain Tumor
• Interventions: Drug: Bevacizumab

• Registration Number: NCT01811498
• Lead Sponsor: Northwell Health

Brief Summary

The high-grade malignant brain tumors, glioblastoma multiforme (GBM), comprise the majority of all primary brain tumors in adults. This group of tumors also exhibits the most aggressive behavior, resulting in median overall survival of only 9-12 months. Initial therapy consists of either surgical resection, external beam radiation, or both. All patients experience a recurrence after first-line therapy, so improvements in both first-line and salvage therapy are critical to enhancing quality-of-life and prolonging survival. It is unknown if currently used intravenous (IV) therapies even cross the blood brain barrier (BBB). We have shown in a previous phase I trial that a single Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab (up to 15mg/kg) is safe and effective in the treatment of recurrent GBM. Therefore, this phase I/II clinical research trial is an extension of that trial in that we seek to test the hypothesis that repeated dosing of intra-arterial Bevacizumab is safe and effective in the treatment of newly diagnosed malignant glioma. By achieving the aims of this study we will also determine if repeated intra-arterial Bevacizumab improves progression free and overall survival in newly diagnosed patients. We expect that this project will provide important information regarding the utility of repeated SIACI Bevacizumab therapy for malignant glioma, and may alter the way these drugs are delivered to our patients in the near future.

Detailed Description

The experimental aspects of this experimental plan will include:

1. Subjects will first be treated with Mannitol prior to chemotherapy infusion (Mannitol 20%; delivered IA, 12.5 mL over 2 minutes) in order to disrupt the blood brain barrier. This technique has been used in several thousand subjects in previous studies for the IA delivery of chemotherapy for malignant glioma.

2. Subjects will then be treated with repeated intraarterial delivery (SIACI) of Bevacizumab. Each subject will receive one dose of IA Bevacizumab on day 30, followed by chemoradiation. SIACI of Bevacizumab will be repeated every three months for a total of 3 infusions.

Study Timeline

• Study Start: 2013-02
• Study First Submitted: 2013-03-12
• Study First Submitted QC: 2013-03-12
• Study First Posted: 2013-03-14
• Primary Completion: 2021-08
• Study Completion: 2021-10
• Results First Submitted: 2022-08-16
• Status Verified: 2024-01
• Results First Submitted QC: 2024-01-23
• Last Update Submitted: 2024-01-23
• Results First Posted: 2024-01-30
• Last Update Posted: 2024-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SIACI of Bevacizumab	Bevacizumab	Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	Percent of Participants with 6 Month Progression-Free Survival	PFS was defined from the date of the first dose of SIACI Bevacizumab until first documentation of disease pro- gression, or death from any cause, whichever occurred first.
Overall Survival (OS)	8 months, and until death of any cause, up to approximately 8 years	Overall Survival was defined from the date of the first dose of SIACI Bevacizumab until death from any cause.

Secondary Outcome Measures

Name	Time	Method
Number of Adverse Events	30 days post treatment	The descriptive frequency of subjects experiencing toxicities will be tabulated.

Trial Locations

Locations (1)

Lenox Hill Brain Tumor Center; 🇺🇸 New York, New York, United States