TTFields and Pulsed Bevacizumab for Recurrent Glioblastoma

NCT ID: NCT02663271

Last Updated: 2022-06-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-19
• Study Completion Date: 2021-06-11

Brief Summary

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.

Detailed 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 bi-monthly. Brain MRI will be performed every 2 months.

Conditions

Glioblastoma Multiforme; Glioblastoma; Malignant Glioma; GBM

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

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

Optune

Intervention Type: DEVICE

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.

Brain MRI

Intervention Type: OTHER

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

Quality of Life Questionnaires

Intervention Type: OTHER

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

Interventions

Bevacizumab

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

Intervention Type: DRUG

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.

Intervention Type: DEVICE

Brain MRI

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

Intervention Type: OTHER

Quality of Life Questionnaires

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

Intervention Type: OTHER

Other Intervention Names

Avastin; NovoTTF™-100A System; Magnetic resonance imaging; Karnofsky Performance Scale; MMSE

Eligibility Criteria

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.

• Minimum Eligible Age: 22 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NovoCure Ltd.

INDUSTRY

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David D Tran, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Gainesville, Florida, United States

Washington University

St Louis, Missouri, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

OCR14874

Identifier Type: OTHER

Identifier Source: secondary_id

IRB201600074

Identifier Type: -

Identifier Source: org_study_id