Description:
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.
Title
- Brief Title: Repeated Super-selective Intraarterial Cerebral Infusion of Bevacizumab (Avastin) for Treatment of Relapsed GBM and AA
- Official Title: Phase I/II Trial Of Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab (Avastin) for Treatment of Relapsed/Refractory Glioblastoma Multiforme and Anaplastic Astrocytoma.
Clinical Trial IDs
- ORG STUDY ID:
14-353
- NCT ID:
NCT01269853
Conditions
- Glioblastoma Multiforme
- Anaplastic Astrocytoma
Interventions
| Drug | Synonyms | Arms |
|---|
| Bevacizumab | | Arm 2 |
| Bevacizumab | | Arm 1 |
Purpose
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.
Detailed Description
The current standard of care for recurring GBM is for patients to receive Bevacizumab
(Avastin) intravenously (IV) at 10mg/kg every two weeks until their tumor grows more than
25%. At that point, these patients are deemed treatment failures and are given another
treatment. Because of the blood brain barrier (BBB) where IV drugs do not penetrate the blood
vessel walls well to get into the brain, no one knows for sure if these IV drugs actually get
into the brain after infusion. We have recently completed a Phase I clinical trial that has
shown that SIACI of Bevacizumab is safe and effective up to a dose of 15mg/kg in patients
with recurrent malignant glioma. This two arm open-label, non-randomized trial is a follow up
study to that trial and will ask two simple questions: Is it safe to deliver repeated doses
of Bevacizumab intraarterially using these super selective intraarterial delivery techniques?
Is it necessary to combine this IA regimen of treatment with biweekly IV Bevacizumab in order
to improve progression free survival (PFS) and overall survival (OS)? Information from this
trial will yield important answers to the durability and efficacy of this delivery technique
and may radically change the way chemotherapy is given to our patients with brain tumors.
Current Standard of Care:
Day 0: Intravenous Bevacizumab (10mg/kg) Day 14, 28 (and every two weeks thereafter):
Intravenous Bevacizumab
Therefore the experimental aspects of this treatment plan will include:
1. Subjects will first be treated with Mannitol prior to chemotherapy infusion (Mannitol
20%; 12.5 mL/s over 2 minutes) in order to disrupt the blood brain barrier. This
technique has been used in several thousand patients in previous studies for the IA
delivery of chemotherapy for malignant glioma. We have used this without complication in
the 30 patients from our Phase I protocol as well.
2. To treat patients with one of two arms with repeated intraarterial delivery (SIACI) of
Bevacizumab for patients with recurring or relapsing high grade glioma. Each arm gets IA
delivery with one arm getting IV Bevacizumab biweekly as well and the other arm not
getting intervening IV therapy. In each arm, IA therapy is repeated when MRI shows
progression. Persistent progression after three intraarterial chemotherapies would
remove the patient from the trial.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm 2 | Experimental | | |
| Arm 1 | Experimental | | |
Eligibility Criteria
Inclusion Criteria:
- 18 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.
Exclusion Criteria:
- 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Composite overall response rate (CORR) |
| Time Frame: | 6 months |
| Safety Issue: | |
| Description: | We will determine this composite overall response rate (CORR) through the Response Assessment in Neuro-Oncology (RANO) criteria |
Secondary Outcome Measures
| Measure: | The safety of repeated SIACI of mannitol and Bevacizumab at 15mg/kg. |
| Time Frame: | 1 month |
| Safety Issue: | |
| Description: | The descriptive frequency of subjects experiencing toxicities will also be tabulated. |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Northwell Health |
Trial Keywords
- GBM
- AA
- AO
- Brain
- Tumors
- Malignant
- Glioblastoma
- Multiforme
- Anaplastic
- Astrocytoma
Last Updated
September 10, 2020
