TTFields and Pulsed Bevacizumab for Recurrent Glioblastoma

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 22 Years and Over
Gender All
More Inclusion & Exclusion 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT02663271
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Florida
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

David D Tran, MD, PhD
Principal Investigator Affiliation University of Florida
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherIndustry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioblastoma Multiforme, Glioblastoma, Malignant Glioma, GBM
Additional Details

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 & Interventions

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.

Other: Historical Controls

Historical controls treated with continuous bevacizumab alone or in combination with standard chemotherapy will be compared with the Optune arm. Information will be collected: Bevacizumab or additional chemotherapy, physical examination and quality of life questionnaires 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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Florida, Gainesville, Florida

Status

Recruiting

Address

University of Florida

Gainesville, Florida, 32611

Site Contact

Deborah Sampson

deborah.sampson@neurosurgery.ufl.edu

352-273-7774

Washington University, Saint Louis, Missouri

Status

Recruiting

Address

Washington University

Saint Louis, Missouri, 63110

Site Contact

Grayson Talcott, BS

wu-grayson@wustl.edu

314-273-0656

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