Prospective, Randomized Controlled Trial of Surgical Resection Prior to Bevacizumab Therapy for Recurrent Glioblastoma Multiforme
The objective of this prospective randomized controlled study is to determine the overall
survival benefit of tumor resection in patients with recurrent glioblastoma multiforme
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.
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.
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
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Median Overall Survival
John K Park, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|