Super-Selective Intraarterial Intracranial Infusion of Avastin (Bevacizumab)
This study has been completed.
Information provided by (Responsible Party):
John A. Boockvar, North Shore Long Island Jewish Health System
First received: August 26, 2009
Last updated: April 20, 2015
Last verified: April 2015
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.
Drug: Super-Selective Intraarterial Intracranial Infusion of BEVACIZUMAB
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Phase I Trial of Super-Selective Intraarterial Intracranial Infusion of Avastin (Bevacizumab) For Treatment of Relapsed/Refractory Glioblastoma Multiforme and Anaplastic Astrocytoma
Primary Outcome Measures:
- To determine the safety of superselective intracranial intraarterial infusion of Avastin up to a dose of 10mg/kg IA. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- 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. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Six-month progression-free survival (PFS) and overall survival (OS) will be assessed by Kaplan-Meier survival analysis, assuming adequate follow-up time. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||January 2014 (Final data collection date for primary outcome measure)
Drug: Super-Selective Intraarterial Intracranial Infusion of BEVACIZUMAB
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.
Other Name: Avastin
|Ages Eligible for Study:
||18 Years and older (Adult, Senior)
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
- 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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00968240
|Lenox Hill Brain Tumor Center
|New York, New York, United States, 10075 |
||John Boockvar, MD
||Weill Cornell Medical College-New York Presbyterian Hospital
||John A. Boockvar, Associate Professor, North Shore Long Island Jewish Health System
History of Changes
|Other Study ID Numbers:
|Study First Received:
||August 26, 2009
||April 20, 2015
||United States: Institutional Review Board
Keywords provided by Northwell Health:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 27, 2016
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Angiogenesis Modulating Agents
Physiological Effects of Drugs