Super-Selective Intraarterial Intracranial Infusion of Avastin (Bevacizumab)

NCT00968240 | Completed Phase 1

• 1 other identifier: 0901010185
• Study Type: interventional
• Target: 30
• 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). Superselective Intraarterial Cerebral Infusion (SIACI) is a technique that can effectively increase the concentration of drug delivered to the brain while sparing the body of systemic side effects. One currently used drug called, Bevacizumab (Avastin) has been shown to be active in human brain tumors but its actual CNS penetration is unknown. This phase I clinical research trial will test the hypothesis that Bevacizumab can be safely used by direct intracranial superselective intraarterial infusion up to a dose of 10mg/kg to ultimately enhance survival of patients with relapsed/refractory GBM/AA. By achieving the aims of this study we will determine the toxicity profile and maximum tolerated dose (MTD of SIACI Bevacizumab. We expect that this project will provide important information regarding the utility of SIACI Bevacizumab therapy for malignant glioma, and may alter the way these drugs are delivered to our 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 (1)

• To determine the safety of superselective intracranial intraarterial infusion of Avastin up to a dose of 10mg/kg IA.

  3 years

Secondary Outcomes (2)

• Composite overall response rate: The composite overall response rate (CORR) will be examined. The overall response proportion along with a 95% confidence interval will be estimated via binomial proportions.

  3 years

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

  3 years

Interventions

Super-Selective Intraarterial Intracranial Infusion of BEVACIZUMAB DRUG

This phase I clinical research trial will test the hypothesis that Bevacizumab can be safely used by direct intracranial superselective intraarterial infusion up to a dose of 10mg/kg to ultimately enhance survival of patients with relapsed/refractory GBM/AA. Day 0: Intraarterial Avastin single dose (starting at 2mg/kg and up to 10mg/kg) after Mannitol to open the blood brain barrier.

Also known as: Avastin

Eligibility Criteria

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

You may qualify if:

• Male or female patients of greater or equal18 years of age.
• Patients with a documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA)
• Patients with a histologically confirmed low-grade brain tumor who relapse with an enhancing tumor on MRI can be evaluated for toxicity only.
• Patients must have at least one confirmed and evaluable tumor site.
• \*A confirmed tumor site is one in 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 greater or equal to 60% (or the equivalent ECOG level of 0-2) (see Appendix A; Performance Status Evaluation) and an expected survival of greater or equal to three months.
• Patients must be able to understand informed consent. Informed consent must be obtained at the time of patient screening.
• Because of known concerns with Avastin and wound healing, all craniotomy patients are eligible for the treatment if they have had a craniotomy \> two weeks prior to IA therapy. Craniotomy after SIACI bevacizumab therapy should wait 4 weeks.
• Pre-enrollment coagulation parameters (PT and PTT) must be less than or equal to1.5X the IUNL.
• Patients must have adequate hematologic reserve with WBC greater than or equal to 2800/mm3, absolute neutrophils greater than or equal to1500/mm3 and platelets greater than or equal to 100,000/ mm3.
• Pre-enrollment chemistry parameters must show: bilirubin\<1.5X the institutional upper limit of normal (IUNL); AST or ALT\<2.5X IUNL and creatinine\<1.5X IUNL.
• No external beam radiation for four weeks prior to treatment under this research protocol.
• No chemotherapy for three weeks prior to treatment under this research protocol.

You may not qualify if:

• Patients previously treated with more than 6 cycles (28 days each) of Bevacizumab at 10/mg/kg.
• 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.

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Lenox Hill Brain Tumor Center

New York, New York, 10075, United States

Location

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

  Weill Cornell Medical College-New York Presbyterian Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 26, 2009
• First Posted: August 28, 2009
• Study Start: July 1, 2009
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: April 22, 2015

Record last verified: 2015-04

Locations

US (1)