This protocol is designed to generate and provide preliminary data to determine the safety and activity of combination therapy using tumor treating fields (TTFields; Optune(NovoTTF-100A); Novocure, Haifa, Israel), a novel FDA-approved therapy utilizing alternating electric fields to inhibit tumor cell growth, along with bevacizumab (Avastin; Genentech, San Francisco, CA), a humanized monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), and hypofractionated stereotactic radiotherapy, a highly-focal abbreviated course of brain irradiation, in the treatment of patients with bevacizumab-naive recurrent GBM. Each of these individual therapies, and also several combinations in doublets, has already demonstrated safety and efficacy but prospective clinical data for the concurrent combination of all three therapies are lacking.
The combination of Optune(NovoTTF) with the active regimen of bevacizumab and hypofractionated stereotactic radiotherapy bases the addition of an effective new treatment in the setting of a safe regimen with favorable survival reports. To date, no clinical data are available on the interaction of concomitant tumor treating fields with radiation therapy either with or without bevacizumab. TTF and radiation both have the potential to enhance the other's therapeutic ratio though synergistic mechanisms of action. The addition of bevacizumab to this regimen has both therapeutic and improved-toxicity implications. A trial combining Optune with the proven regimen of HFSRT and bevacizumab for recurrent glioblastoma affords an avenue to demonstrate safety in a population who may more readily derive a benefit from novel multimodality therapy and explore the potential for synergistic effect. The endpoint of efficacy would clearly need to be more definitively addressed in a future categorical trial, which would be the logical positive outcome of this pilot study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Ummc Msgcc
Baltimore, Maryland, United States
Number of Participants With a Grade 3 or High Toxicity/Adverse Event (Primary Measure)
The ability to complete protocol treatment (i.e. tri-modality treatment) without undue acute toxicity as defined below * : \<40% rate of Grade 3 or higher nonhematologic toxicity. * : \<15% rate of Grade 4 or higher nonhematologic toxicity * : \<5% rate of Grade 4+ scalp dermatitis * : \<50% rate of Grade 2-3 scalp dermatitis Early stopping rules: Two or more Grade 2 or higher symptomatic CNS hemorrhages; Eight treatment-related Grade 3 or higher non hematologic or Grade 4 or higher hematologic toxicities.
Time frame: 6 months
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