Clinical trial NCT01811498: Repeated Super-Selective Intraarterial Cerebral Infusion of Bevacizumab (Avastin) for Treatment of Newly Diagnosed GBM
Official title: Phase I/II Trial of Repeated Super-Selective Intraarterial Cerebral Infusion of Bevacizumab (Avastin) for Treatment of Newly Diagnosed Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Glioblastoma Multiforme
Brain Tumor
Lead sponsor: Northwell Health
Sponsor class: OTHER
Collaborators: name: Feinstein Institute for Medical Research
First posted: 2013-03-14
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Percent of Participants with 6 Month Progression-Free Survival
measure: Overall Survival (OS)
timeFrame: 8 months, and until death of any cause, up to approximately 8 years
Secondary outcomes:
measure: Number of Adverse Events
timeFrame: 30 days post treatment
Other outcomes:
Locations:
city: New York
country: United States
facility: Lenox Hill Brain Tumor Center
state: New York
Study officials:
affiliation: Feinstein Institute for Medical Research
name: John Boockvar, MD
role: PRINCIPAL_INVESTIGATOR
References: