Glioblastoma multiforme (GBM) is the most common and deadliest primary malignant neoplasm
of the central nervous system in adults. Despite an aggressive multimodality treatment
approach including surgery, radiation therapy and chemotherapy, overall survival remains
poor. Novocure has shown that when properly tuned, very low intensity, intermediate
frequency electric fields (TTFields) stunt the growth of tumor cells. The Optune system
(NovoTTFTM Therapy) is a portable battery operated device, which produces TTFields within
the human body by means of surface transducer arrays. The TTFields are applied to the
patient by means of surface transducer arrays that are electrically insulated, so that
resistively coupled electric currents are not delivered to the patient. Optune is
currently FDA-approved as a single modality treatment for recurrent GBM when both
surgical and radiotherapy options have been exhausted as well as combination with
adjuvant temozolomide for newly diagnosed GBM.
This research study is being performed to determine whether or not TTFields combined with
pulsed bevacizumab treatment increases overall survival in patients with
bevacizumab-refractory GBM compared to historical controls treated with continuous
bevacizumab alone or in combination with other chemotherapy.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02663271.
Subjects who have evidence of bevacizumab-refractory GBM will be eligible to participate
in this research study. Subjects will undergo 12 months of planned continuous treatment
with TTFields followed by pulsed bevacizumab treatment when there is evidence of further
progression per RANO, with the option of extending treatment up to a total of 24 months
in patients who have not progressed and/or have adequate performance status at the 12
month mark. Pulsed bevacizumab dosing is defined by at least one cycle on and at least
one cycle off. A cycle is defined as 8 weeks in length. If after one cycle on, there is
no evidence of a repeat response; bevacizumab will be continued for one more cycle. If
after two cycles on, there is no repeat response; bevacizumab will be continued with or
without other standard chemotherapy until death. If after at least one cycle on, there is
evidence of repeat response, bevacizumab will be discontinued for at least one cycle or
until progression is noted again per RANO, whichever is later, at which time pulsed
bevacizumab will be restarted as outlined above. The investigators believe that this
approach will produce peaks and troughs in mitotic activities of glioma cells that render
glioma cells more sensitive to the antimitotic activity of Optune during peak growth
rates, thus lowering disease burden and increasing survival. In addition, the following
will be performed: Bevacizumab will be given at 10mg/kg IV every 2 weeks. Physical
examination and quality of life (QoL) assessments will be performed bi-monthly. Brain MRI
will be performed every 2 months.
Lead OrganizationUF Health Cancer Institute - Gainesville
