Glioblastoma MultiformePhase 2NCT02663271
TTFields and Pulsed Bevacizumab for Recurrent Glioblastoma
A Phase 2 study testing Bevacizumab, Optune and Brain MRI in people with Glioblastoma Multiforme and Glioblastoma, run by University of Florida at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 22 years and older
- Conditions the study is for
- Glioblastoma Multiforme, Glioblastoma, Malignant Glioma
- What is being tested?
- Bevacizumab, Optune and Brain MRI
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- 19 Dec 2016to 11 Jun 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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 locations and contacts
2 sites in 1 country.
United States2 sites
University of Florida
Gainesville, Florida, 32611
Washington University
St Louis, Missouri, 63110
About this study
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
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.
Read the 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
- Being tested
- Bevacizumab, Optune, Brain MRI, Quality of Life Questionnaires
- Medical subject headings
- Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
Bevacizumab will be given at 10mg/kg IV every 2 weeks.
OptuneDevice
Also called NovoTTF™-100A System
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 MRIOther
Also called Magnetic resonance imaging
Brain MRI will be done at screening and every 8 weeks.
Quality of Life QuestionnairesOther
Also called Karnofsky Performance Scale, MMSE
The quality of life questionnaires will be performed within 14 days of treatment and every 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Optune+Pulsed Bevacizumab | Experimental | 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. Receives: Drug: Bevacizumab; Device: Optune; Other: Brain MRI; Other: Quality of Life Questionnaires |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Overall survival is defined as time interval from date of starting Optune to date of death or censoring whichever happens first.
Measured: from date of starting Optune to date of death or censoring, whichever comes first, assessed up to 24 months
Secondary outcomes (3)
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.
Measured: Assessed up to 24 months
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.
Measured: Assessed up to 24 months
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.
Measured: Assessed up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2016 (estimated)
- Study start19 Dec 2016
- Primary completion11 Jun 2021
- Study completion11 Jun 2021
Why it stopped: stagnant enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- NovoCure Ltd.
- Responsible party
- Sponsor
- Investigators
- David D Tran, MD, PhD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02663271
- Sponsor's protocol ID
- IRB201600074
- Other IDs
- OCR14874
- Status last verified
- May 2022
- First submitted
- 21 Jan 2016
- Last updated
- 23 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02663271
- Acronym / sponsor ID
- IRB201600074
- Conditions
- Glioblastoma Multiforme, Glioblastoma, Malignant Glioma, GBM
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: stagnant enrollment
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- NovoCure Ltd.
- Study start
- 19 Dec 2016 (actual)
- Primary completion
- 11 Jun 2021 (actual)
- Study completion
- 11 Jun 2021 (actual)
- First posted
- 26 Jan 2016 (estimated)
- Results
- Posted 23 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Optune+Pulsed Bevacizumab | Experimental | Drug: Bevacizumab, Device: Optune, Other: Brain MRI, Other: Quality of Life QuestionnairesThe 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. |
Who may qualify
- Ages
- 22 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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%.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: AvastinBevacizumab will be given at 10mg/kg IV every 2 weeks. | Drug | Optune+Pulsed Bevacizumab |
| OptuneAlso: NovoTTF™-100A SystemOptune 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. | Device | Optune+Pulsed Bevacizumab |
| Brain MRIAlso: Magnetic resonance imagingBrain MRI will be done at screening and every 8 weeks. | Other | Optune+Pulsed Bevacizumab |
| Quality of Life QuestionnairesAlso: Karnofsky Performance Scale, MMSEThe quality of life questionnaires will be performed within 14 days of treatment and every 4 weeks. | Other | Optune+Pulsed Bevacizumab |
Primary outcome
Overall Survival
Time frame: from date of starting Optune to date of death or censoring, whichever comes first, assessed up to 24 months
Overall survival is defined as time interval from date of starting Optune to date of death or censoring whichever happens first.
3 secondary outcomes
Karnofsky Performance Scale
Time frame: Assessed up to 24 months
Mini-Mental Status Exam
Time frame: Assessed up to 24 months
Response Assessment in Neuro-Oncology (RANO) Measurement Form
Time frame: Assessed up to 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David D Tran, MD, PhD principal investigator
University of Florida
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab, Optune and Brain MRI in people with Glioblastoma Multiforme and Glioblastoma, run by University of Florida at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: from date of starting Optune to date of death or censoring, whichever comes first, assessed up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2022.