Back to resultsTTFields and Pulsed Bevacizumab for Recurrent Glioblastoma
Primary Purpose
Glioblastoma Multiforme, Glioblastoma, Malignant Glioma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bevacizumab
Optune
Brain MRI
Quality of Life Questionnaires
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma Multiforme
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.
Sites / Locations
- University of Florida
- Washington University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Optune+Pulsed Bevacizumab
Arm Description
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.
Outcomes
Primary Outcome Measures
Overall Survival
Overall survival is defined as time interval from date of starting Optune to date of death or censoring whichever happens first.
Secondary Outcome Measures
Karnofsky Performance Scale
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.
Mini-Mental Status Exam
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.
Response Assessment in Neuro-Oncology (RANO) Measurement Form
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.
Full Information
NCT ID
NCT02663271
First Posted
January 21, 2016
Last Updated
May 31, 2022
Sponsor
University of Florida
Collaborators
NovoCure Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT02663271
Brief Title
TTFields and Pulsed Bevacizumab for Recurrent Glioblastoma
Official 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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Terminated
Why Stopped
stagnant enrollment
Study Start Date
December 19, 2016 (Actual)
Primary Completion Date
June 11, 2021 (Actual)
Study Completion Date
June 11, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
Collaborators
NovoCure Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme, Glioblastoma, Malignant Glioma, GBM
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Optune+Pulsed Bevacizumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Bevacizumab will be given at 10mg/kg IV every 2 weeks.
Intervention Type
Device
Intervention Name(s)
Optune
Other Intervention Name(s)
NovoTTF™-100A System
Intervention Description
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
Other
Intervention Name(s)
Brain MRI
Other Intervention Name(s)
Magnetic resonance imaging
Intervention Description
Brain MRI will be done at screening and every 8 weeks.
Intervention Type
Other
Intervention Name(s)
Quality of Life Questionnaires
Other Intervention Name(s)
Karnofsky Performance Scale, MMSE
Intervention Description
The quality of life questionnaires will be performed within 14 days of treatment and every 4 weeks.
Primary Outcome Measure Information:
Title
Overall Survival
Description
Overall survival is defined as time interval from date of starting Optune to date of death or censoring whichever happens first.
Time Frame
from date of starting Optune to date of death or censoring, whichever comes first, assessed up to 24 months
Secondary Outcome Measure Information:
Title
Karnofsky Performance Scale
Description
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.
Time Frame
Assessed up to 24 months
Title
Mini-Mental Status Exam
Description
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.
Time Frame
Assessed up to 24 months
Title
Response Assessment in Neuro-Oncology (RANO) Measurement Form
Description
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.
Time Frame
Assessed up to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David D Tran, MD, PhD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
TTFields and Pulsed Bevacizumab for Recurrent Glioblastoma
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