Repeated Super-Selective Intraarterial Cerebral Infusion of Bevacizumab (Avastin) for Treatment of Newly Diagnosed GBM
| Status: | Recruiting |
|---|---|
| Conditions: | Brain Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/17/2018 |
| Start Date: | February 2013 |
| End Date: | January 2020 |
| Contact: | John Boockvar, MD |
| Email: | jboockvar@nshs.edu |
| Phone: | 212-434-3905 |
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.
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.
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.
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.
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.
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