Repeated Super-selective Intraarterial Cerebral Infusion of Bevacizumab (Avastin) for Treatment of Relapsed GBM and AA

NCT01269853 | Recruiting Phase 1

• 1 other identifier: 14-353
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The high-grade malignant brain tumors, glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), 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 durations of only 9-12 months for GBM, and 3-4 years for AA. 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). The investigators have shown in a previous phase I trial that a single Super-selective 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 the investigators seek to test the hypothesis that repeated dosing of intraarterial Bevacizumab is safe and effective in the treatment of recurrent malignant glioma. By achieving the aims of this study the investigators will also determine if IV therapy with Bevacizumab should be combined with repeated selected intraarterial Bevacizumab to improve progression free and overall survival. The investigators 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 the patients in the near future.

Conditions

Glioblastoma Multiforme; Anaplastic Astrocytoma

Keywords

GBM; AA; AO; Brain; Tumors; Malignant; Glioblastoma; Multiforme; Anaplastic; Astrocytoma

Outcome Measures

Primary Outcomes (2)

• Composite overall response rate (CORR)

  We will determine this composite overall response rate (CORR) through the Response Assessment in Neuro-Oncology (RANO) criteria

  6 months

• Progression-free survival (PFS) and overall survival (OS)

  Six-month progression-free survival (PFS) and overall survival (OS) will be assessed by Kaplan-Meier survival analysis, assuming adequate follow-up time

  6 month

Secondary Outcomes (1)

• The safety of repeated SIACI of mannitol and Bevacizumab at 15mg/kg.

  1 month

Study Arms (2)

Arm 2

EXPERIMENTAL

Drug: Bevacizumab

Arm 1

EXPERIMENTAL

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

Experimental portion of this proposal: This trial will have two experimental arms that will be open labeled and non-randomized. ARM 1 (If the patient has multifocal disease or leptomeningeal disease) Day 0: Intraarterial Bevacizumab single dose (15mg/kg) after Mannitol to open the blood brain barrier Day 28: Intravenous Bevacizumab (10mg/kg) every two weeks thereafter until disease progression on MRI scan. If progression occurs, repeat Intraarterial Bevacizumab single dose (15mg/kg) to area of progression and wait 28 days and then restart Intravenous Bevacizumab (10mg/kg) every two weeks thereafter until progression on MRI scan. Repeat Cycle

Arm 2

Eligibility Criteria

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

You may qualify if:

• years of age or older.
• Patients with a documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA).
• Patients must have at least one confirmed and evaluable tumor site. A confirmed tumor site is one in which is biopsy-proven.
• Patients must have a Karnofsky performance status 70% (or the equivalent ECOG level of 0-2).
• Patients must agree to use a medically effective method of contraception during and for a period of three months after the treatment period.

You may not qualify if:

• Previous treatment with greater than 2 cycles of Bevacizumab at 10mg/kg (2 IV Infusions).
• Women who are pregnant or lactating.
• Patients with significant inter-current 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.

Sponsors & Collaborators

• Northwell Health: lead
• Feinstein Institute for Medical Research: collaborator

Study Sites (1)

Lenox Hill Brain Tumor Center

New York, New York, 10065, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Astrocytoma; Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; 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

• John Boockvar, MD

  Feinstein Institute for Medical Research

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Boockvar, MD

CONTACT

212-434-3905; jboockvar@nshs.edu

Tamika Wong, MPH

CONTACT

212-434-4836; twong4@nshs.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 22, 2010
• First Posted: January 4, 2011
• Study Start: October 1, 2010
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: April 9, 2025

Record last verified: 2025-04

Locations

US (1)