Protocol Summary

Protocol No.: OCR14874

Sponsor Protocol No.: 201600074

Study Title
A Phase 2, Multi-center, Single arm, Histologically Controlled Study Testing the Combination of TTFields and Pulsed Bevacizumab Treatment in Patients with Bevacizumab-refractory Recurrent Glioblastoma

Principal Investigator(s)
Tran, David

Objective
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.

Description
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 monthly. Brain MRI will be performed every 2 months.

Phase: Phase II

Age Group: Adult

Scope: National

Treatment
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.

Detailed Eligibility
INCLUSION CRITERIA:
1. Ages 22 years old and older
2. Histologically confirmed GBM, WHO grade IV. GBM variants and secondary GBM are allowed.
3. Unequivocal evidence of tumor progression during prior bevacizumab treatment per RANO criteria.
4. Patient is a candidate for, and agrees to proceed with additional bevacizumab treatment.
5. Karnofsky Performance Scale (KPS) ≥ 60%.
6. Planned treatment with TTFields therapy.
7. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of treatment.
8. Participants of childbearing/reproductive potential must use effective contraception.
9. Participants must be able to understand and willing to comply with protocol requirements as assessed by the investigator.

EXCLUSION CRITERIA:
1. Inability to undergo brain MRI due to medical or personal reasons.
2. Currently receiving investigational agents that are intended as treatments of recurrent GBM.
3. Skull defect such as missing bone or bullet fragments.
4. 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.
5. Intracranial hemorrhage except for tumor associated micro hemorrhage.
6. Women who are pregnant or breastfeeding.
7. Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, vagus nerve stimulator, and other implanted electronic devices in the brain or the spinal cord.
8. Tumor located entirely in the infratentorium.
9. History of hypersensitivity to hydrogel.

Applicable Disease Sites

Brain and Nervous System

Participating Institutions
UF Gainesville : Sonisha Warren
Washington University

Contact
Sonisha Warren, PhD
Phone: +1 352-294-8737
Email: sonisha.warren@neurosurgery.ufl.edu

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT02663271