Clinical Trial Finder

Inclusion Criteria:

• - Histologically confirmed GBM, WHO grade IV.

GBM variants and secondary GBM are allowed in any recurrence (including multiple) and have been treated with radiation and chemotherapy.

• - Unequivocal evidence of tumor progression during prior bevacizumab treatment per RANO criteria.

• - Patient is a candidate for, and agrees to proceed with additional bevacizumab treatment.

• - Male or female at least 22 years of age or older.

• - Karnofsky Performance Scale (KPS) ≥ 60%.

• - Planned treatment with TTFields therapy.

• - Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of treatment.

• - Participants of childbearing/reproductive potential must use effective contraception.

• - Participants must be able to understand and willing to comply with protocol requirements as assessed by the investigator.

• - Signed informed consent according to institutional guidelines prior to registration.

Exclusion Criteria:

• - Inability to undergo brain MRI due to medical or personal reasons.

• - Currently receiving investigational agents that are intended as treatments of recurrent GBM.

• - Skull defect such as missing bone or bullet fragments.

• - Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, heart attack within the previous 12 months, stroke (except for TIA) within the previous 6 months, or psychiatric illness/social situations that would limit compliance with study requirements.

• - Intracranial hemorrhage except for tumor associated micro hemorrhage.

• - Women who are pregnant or breastfeeding.

• - Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, vagus nerve stimulator, and other implanted electronic devices in the brain or the spinal cord.

• - Tumor located entirely in the infratentorium.

• - History of hypersensitivity to hydrogel.

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.

Arms

Experimental: Optune+Pulsed Bevacizumab

The subjects will undergo 12 months of planned continuous treatment with Optune. The treatment will begin at week 0 and will be continuous throughout the study. 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. In addition, the following will be performed: Bevacizumab will be given, physical examination and quality of life questionnaires will be performed and brain MRI.

Interventions

Drug: - Bevacizumab

Bevacizumab will be given at 10mg/kg IV every 2 weeks.

Device: - Optune

Optune will be worn continuously for 12 months. Optune is programmed by Novocure to deliver 200 kHz TTFields in two sequential, perpendicular field directions at a maximal intensity of 707mARMS. There will be no adjustments made to the device by investigators or patients/caregivers.

Other: - Brain MRI

Brain MRI will be done at screening and every 8 weeks.

Other: - Quality of Life Questionnaires

The quality of life questionnaires will be performed within 14 days of treatment and every 4 weeks.