- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02663271
TTFields and Pulsed Bevacizumab for Recurrent Glioblastoma
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
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 Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Florida
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Gainesville, Florida, United States, 32611
- University of Florida
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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Bevacizumab will be given at 10mg/kg IV every 2 weeks.
Other Names:
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 Names:
Brain MRI will be done at screening and every 8 weeks.
Other Names:
The quality of life questionnaires will be performed within 14 days of treatment and every 4 weeks.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: from date of starting Optune to date of death or censoring, whichever comes first, assessed up to 24 months
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Overall survival is defined as time interval from date of starting Optune to date of death or censoring whichever happens first.
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from date of starting Optune to date of death or censoring, whichever comes first, assessed up to 24 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Karnofsky Performance Scale
Time Frame: Assessed up to 24 months
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The Karnofsky Performance Scale is rated from 0 - 100 with 0 = death and 100 = normal without complaints or evidence of disease.
A higher score means the patient is better able to carry out daily activities.
Patients are evaluable for assessment of QoL after completing at least 8 weeks of treatment with the Optune device with compliance rate > 60% in at least one 4-week period.
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Assessed up to 24 months
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Mini-Mental Status Exam
Time Frame: Assessed up to 24 months
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The Mini Mental State Examination (MMSE) it is an 11-question measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall, and language.
The maximum score is 30.
The higher the score suggests less cognitive impairment.
A score of 24-30 suggests no cognitive impairment.
A score of 18-23 suggests mild cognitive impairment.
A score of 0-17 suggests severe cognitive impairment.
Patients are evaluable for assessment of QoL after completing at least 8 weeks of treatment with the Optune device with compliance rate > 60% in at least one 4-week period.
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Assessed up to 24 months
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Response Assessment in Neuro-Oncology (RANO) Measurement Form
Time Frame: Assessed up to 24 months
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The Response Assessment in Neuro-Oncology criteria were developed as an objective tool for radiologic assessment of treatment response in high-grade gliomas.
Disease progression is defined as ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions (with the absolute increase of at least 1 dimension of at least 5 mm) compared with the smallest tumor measurement obtained either at baseline.
Response assessment will be performed for patients completing at least 8 weeks of treatment with the Optune device with compliance rate > 60% in at least one 4-week period.
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Assessed up to 24 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: David D Tran, MD, PhD, University of Florida
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Astrocytoma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Glioblastoma
- Glioma
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Bevacizumab
Other Study ID Numbers
- IRB201600074
- OCR14874 (Other Identifier: University of Florida)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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