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

January 23, 2024 updated by: John Boockvar, MD Zucker SOM @Hofstra/Northwell, Northwell Health

Phase I/II Trial of Repeated Super-Selective Intraarterial Cerebral Infusion of Bevacizumab (Avastin) for Treatment of Newly Diagnosed Glioblastoma Multiforme

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Lenox Hill Brain Tumor Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Criteria for Inclusion:

  • Male or female patients of ≥18 years of age.
  • Patients with documented histologic diagnosis of glioblastoma multiforme (newly diagnosed)

  • Patients must have at least one confirmed and evaluable tumor site.∗

    *A confirmed tumor site is one which is biopsy-proven. NOTE: Radiographic procedures (e.g., Gd-enhanced MRI or CT scans) documenting existing lesions must have been performed within three weeks of treatment on this research study.

  • Patients must have a Karnofsky performance status ≥70% (or the equivalent ECOG level of 0-2) and an expected survival of ≥ three months.
  • Patients must agree to use a medically effective method of contraception during and for a period of three months after the treatment period. A pregnancy test will be performed on each premenopausal female of childbearing potential immediately prior to entry into the research study.

Criteria for Exclusion:

  • Previous treatment with Bevacizumab.
  • Women who are pregnant or lactating.
  • Women of childbearing potential and fertile men who decline to use effective contraception during and for a period of three months after the treatment period.
  • Patients with significant intercurrent medical or psychiatric conditions that would place them at increased risk or affect their ability to receive or comply with treatment or post-treatment clinical monitoring.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SIACI of Bevacizumab
Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab
Drug: Bevacizumab
Other Names:
  • Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: 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.
Percent of Participants with 6 Month Progression-Free Survival
Overall Survival (OS)
Time Frame: 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.
8 months, and until death of any cause, up to approximately 8 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Adverse Events
Time Frame: 30 days post treatment
The descriptive frequency of subjects experiencing toxicities will be tabulated.
30 days post treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwell Health

Collaborators

Feinstein Institute for Medical Research

Investigators

  • Principal Investigator: John Boockvar, MD, Feinstein Institute for Medical Research

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2013

Primary Completion (Actual)

August 1, 2021

Study Completion (Actual)

October 1, 2021

Study Registration Dates

First Submitted

March 12, 2013

First Submitted That Met QC Criteria

March 12, 2013

First Posted (Estimated)

March 14, 2013

Study Record Updates

Last Update Posted (Actual)

January 30, 2024

Last Update Submitted That Met QC Criteria

January 23, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14-352

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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