The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, is looking for individuals to participate in clinical studies. Participating in clinical trials allows you to play an active role in research on the nature and causes of many disorders of the brain and nervous system, and to possibly help physician-scientists develop future treatments. The information below is designed to help you quickly learn about actively recruiting research studies for which you or someone you know may be eligible.


Objective The objective of this prospective randomized controlled study is to determine the overall survival benefit of tumor resection in patients with recurrent glioblastoma multiforme (GBM). Study Population This study will recruit 42 adults with a diagnosis of recurrent grade 4 astrocytoma into each of two arms, for a total of 84 patients. All participants will be good candidates for elective surgical resection of their tumors according to the previously established NIH Recurrent Glioma Scale (NRGS), which uses performance status, tumor volume, and tumor involvement of critical/eloquent brain areas as prognostic criteria. Patients who require biopsy only or have previously been treated with bevacizumab will be excluded. Design Participants will be stratified by NRGS score (NRGS 0 or NRGS 1-2) and randomized to surgery followed by bevacizumab or to bevacizumab alone. Patients assigned to the surgical arm will undergo their procedure within 28 days of randomization. Treatment with bevacizumab at a dose of 10 mg/kg every 2 weeks will begin at least 28 days later to allow adequate craniotomy wound healing. Patients assigned to the non-surgical arm will start bevacizumab at a dose of 10 mg/kg every 2 weeks immediately. MRI evaluations will take place within 72 hours of surgery to assess extent of resection, 28 days postoperatively, 96 hours after starting bevacizumab, and then every 28 days until tumor progression is documented. Follow-up assessments will take place every 28 days while on bevacizumab until tumor progression. Once progression is established, patients will be free to pursue further surgical and/or medical salvage therapy as they wish. Patients will be followed until their time of death. Outcome Measures The primary outcome measure is median overall survival from the date bevacizumab is started. Secondary outcome measures include the rate of progression-free survival 6 months after starting bevacizumab, median progression-free survival, overall survival rates at 6 and 12 months after starting bevacizumab, objective response rate, health-related quality of life, change in KPS of 20 points or more, time to need for additional tumor therapy, and use of corticosteroids.

Eligibility Criteria:

- INCLUSION CRITERIA: Previous diagnosis of supratentorial GBM established by WHO histological criteria Age 18 or older NRGS score of 0 to 2 established by the following criteria: - KPS 80 or less (1 point) - Tumor volume 50 cc or greater (1 point) - Tumor involvement of at least 2 of the following brain areas (1 point): - Motor cortex - Language cortex - Areas directly adjacent to the proximal (M1 and/or M2) middle cerebral artery Received initial treatment for GBM with: - External beam radiation therapy - Nitrosourea or temozolomide chemotherapy - Biopsy, subtotal or gross total resection Evidence of recurrence, defined as the appearance or enlargement since previous imaging of a contrast-enhancing mass on T1-weighted MRI Have a non-deep (involving basal ganglia, thalamus, or periventricular region), non-diffuse recurrence judged to be resectable by a neurosurgeon Able to provide informed consent EXCLUSION CRITERIA: NRGS score of 3 Patients requiring biopsy only or other procedures where the goal is not tumor cytoreduction Patients who require urgent or emergency surgery due to symptoms of raised intracranial pressure or herniation Patients who have already received bevacizumab therapy Contraindication to surgery as determined by a neurosurgeon, including bleeding diathesis, unacceptable pulmonary or cardiovascular risk, significant wound healing concerns, or tumor recurrence judged to be inoperable, inaccessible, or diffuse Contraindication to bevacizumab as determined by a neuro-oncologist, including unacceptable end organ function, evidence of acute intracranial hemorrhage, or recent or active use of anticoagulants Contraindication to MRI scanning as determined by a radiologist, including pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or shrapnel fragments Pregnancy

Study Design: