Prospective, Randomized Controlled Trial of Surgical Resection Prior to Bevacizumab Therapy for Recurrent Glioblastoma Multiforme
18 Years
N/A
Both
Glioblastoma, Brain Neoplasm
Trial Information
Prospective, Randomized Controlled Trial of Surgical Resection Prior to Bevacizumab Therapy for Recurrent Glioblastoma Multiforme
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Median Overall Survival
Outcome Time Frame:
2 years
Safety Issue:
No
Principal Investigator
John K Park, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
National Institute of Neurological Disorders and Stroke (NINDS)
Authority:
United States: Federal Government
Study ID:
110204
NCT ID:
NCT01413438
Start Date:
July 2011
Completion Date:
December 2020
Related Keywords:
- Glioblastoma
- Brain Neoplasm
- Bevacizumab
- Quality of Life
- Glioblastoma Multiforme
- Neurosurgery
- Glioblastoma
- GBM
- Brain Tumor
- Brain Neoplasms
- Neoplasms
- Glioblastoma
Name | Location |
|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |
