Brain Tumor, Glioblastoma Multiforme
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGBevacizumab
Sponsors
Feinstein Institute for Medical Research
Northwell Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Percent of Participants with 6 Month Progression-Free Survival | PFS was defined from the date of the first dose of SIACI Bevacizumab until first documentation of disease pro- gression, or death from any cause, whichever occurred first. |
| Overall Survival (OS) | 8 months, and until death of any cause, up to approximately 8 years | Overall Survival was defined from the date of the first dose of SIACI Bevacizumab until death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events | 30 days post treatment | The descriptive frequency of subjects experiencing toxicities will be tabulated. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SIACI of Bevacizumab Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab
Bevacizumab | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | SIACI of Bevacizumab |
|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 12.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 23 |
| other Total, other adverse events | 16 / 23 |
| serious Total, serious adverse events | 0 / 23 |
Outcome results
Primary
Overall Survival (OS)
Overall Survival was defined from the date of the first dose of SIACI Bevacizumab until death from any cause.
Time frame: 8 months, and until death of any cause, up to approximately 8 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SIACI of Bevacizumab | Overall Survival (OS) | 23.1 months |
Primary
Progression-free Survival (PFS)
PFS was defined from the date of the first dose of SIACI Bevacizumab until first documentation of disease pro- gression, or death from any cause, whichever occurred first.
Time frame: Percent of Participants with 6 Month Progression-Free Survival
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SIACI of Bevacizumab | Progression-free Survival (PFS) | 91.3 percentage of participants |
Secondary
Number of Adverse Events
The descriptive frequency of subjects experiencing toxicities will be tabulated.
Time frame: 30 days post treatment
Population: Total of 23 participants some who had multiple AE's therefore the adverse events number exceeds particpants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SIACI of Bevacizumab | Number of Adverse Events | Grade 1 Adverse Events | 31 Adverse events |
| SIACI of Bevacizumab | Number of Adverse Events | Grade 2 Adverse Events | 15 Adverse events |
| SIACI of Bevacizumab | Number of Adverse Events | Grade 3 Adverse Events | 12 Adverse events |