RECURRENT GLIOBLASTOMANCT01925573
Optune(NOVOTTF-100A)+ Bevacizumab+ Hypofractionated Stereotactic Irradiation Bevacizumab-Naive Recurrent Glioblastoma (GCC 1344)
A study testing Optune(NOVOTTF-100A) in people with RECURRENT GLIOBLASTOMA and Brain Tumor, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
This protocol is designed to generate and provide preliminary data to determine the safety and activity of combination therapy using tumor treating fields (TTFields; Optune(NovoTTF-100A); Novocure, Haifa, Israel), a novel FDA-approved therapy utilizing alternating electric fields to inhibit tumor cell growth, along… Read more about this study
- Who is it for?
- Ages 22 years and older
- Conditions the study is for
- RECURRENT GLIOBLASTOMA, Brain Tumor
- What is being tested?
- Optune(NOVOTTF-100A)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to Aug 2019
- Phase
- Interventional
- 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
- 1 Patients with recurrent or progressive glioblastoma or other grade IV malignant glioma (i.e. glioblastoma, gliosarcoma, giant cell glioblastoma, etc.) who have failed prior radiation but who have not progressed/recurred on bevacizumab. Patients will be eligible if the original histology was lower-grade glioma and subsequent diagnosis of glioblastoma or gliosarcoma is made.
- 2 Patients with any number of recurrences are allowed. 3 Brain MRI demonstrates an enhancing tumor < 8 cm in largest diameter. 4 Karnofsky performance status ≥ 70%. 5 Age ≥ 22 years old. 6 Patients must have the following laboratory values:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- Hemoglobin (Hgb) > 10 g/dL
- Serum total bilirubin: ≤ 1.5 x ULN
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- ALT and AST ≤ 3.0 x ULN
- Adequate Renal Function: BUN and Cr < 2.0 x ULN
- Blood coagulation parameters: international normalized ratio (INR) ≤ 1.5 for patients not on warfarin 7 Minimum interval since completion of radiation treatment is 12 weeks. 8 History of standard dose CNS radiotherapy: radiation of 60 Gy in 30 fractions or 59.4 Gy in 1.8 Gy fractions, or equivalent or lower doses.
- 9 Minimum interval since last major surgery, open biopsy, or significant traumatic injury is 4 weeks 10 Minimum interval since last drug therapy:
- 3 weeks since last non-cytotoxic therapy
- 3 weeks must have elapsed since the completion of a non-nitrosourea-containing chemotherapy regimen
- 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen. 11 Patients must have signed an approved informed consent and authorization permitting release of personal health information.
- 12 Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Female patients of child-bearing potential must have a negative pregnancy test.
- 13 Patients with history of prior invasive malignancy (except non-melanomatous skin cancer) must have been disease free for a minimum of 1 year.
- 14 Patients must be maintained on a stable corticosteroid regimen from the time of their baseline scan until the start of treatment and/or for at least 5 days before starting treatment.
- 15 Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria: 16 No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices) 17 In-range INR (max ≤ 3) on a stable dose of oral anticoagulant for greater than 1 month or on a stable dose of low molecular weight heparin
Who cannot join
- 1 Any prior therapy with bevacizumab 2 Any significant hemorrhage defined as > 1 cm diameter of blood seen on the MRI or CT scan. If > 1 cm of acute blood is detected, the patient will be ineligible for this trial.
- 3 Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury.
- 4 Patients with impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- History or presence of serious uncontrolled ventricular arrhythmias
- Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)
- Uncontrolled hypertension (defined by a SBP ≥ 160 mm Hg or DBP ≥ 100 mm Hg while on anti-hypertensive medications) or history of hypertensive crisis or hypertensive encephalopathy, stroke, TIA, symptomatic peripheral vascular disease, or grade 2 CHF 5 Patients with cirrhosis, or active viral or non-viral hepatitis. 6 Patients with peptic ulcer, abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within 6 months of enrollment.
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- 7 Implanted pacemaker, defibrillator or deep brain stimulator, other implanted electronic devices in the brain or documented clinically significant arrhythmias.
- 8 Infra-tentorial tumor. 9 Known sensitivity to conductive hydrogels. 10 Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory).
- 11 Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol 12 Pregnant or breast-feeding women. 13 Patients unwilling or unable to comply with the protocol. 14 Patients treated on any other therapeutic clinical protocols within 3 weeks of starting on this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Proposed Pilot Study of Combined Optune+ Bevacizumab, and Hypofractionated Stereotactic Irradiation for Bevacizumab-Naive Recurrent Glioblastoma
This protocol is designed to generate and provide preliminary data to determine the safety and activity of combination therapy using tumor treating fields (TTFields; Optune(NovoTTF-100A); Novocure, Haifa, Israel), a novel FDA-approved therapy utilizing alternating electric fields to inhibit tumor cell growth, along with bevacizumab (Avastin; Genentech, San Francisco, CA), a humanized monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), and hypofractionated stereotactic radiotherapy, a highly-focal abbreviated course of brain irradiation, in the treatment of patients with bevacizumab-naive recurrent GBM. Each of these individual therapies, and also several combinations in doublets, has already demonstrated safety and efficacy but prospective clinical data for the concurrent combination of all three therapies are lacking.
Read the detailed description
The combination of Optune(NovoTTF) with the active regimen of bevacizumab and hypofractionated stereotactic radiotherapy bases the addition of an effective new treatment in the setting of a safe regimen with favorable survival reports. To date, no clinical data are available on the interaction of concomitant tumor treating fields with radiation therapy either with or without bevacizumab. TTF and radiation both have the potential to enhance the other's therapeutic ratio though synergistic mechanisms of action. The addition of bevacizumab to this regimen has both therapeutic and improved-toxicity implications. A trial combining Optune with the proven regimen of HFSRT and bevacizumab for recurrent glioblastoma affords an avenue to demonstrate safety in a population who may more readily derive a benefit from novel multimodality therapy and explore the potential for synergistic effect. The endpoint of efficacy would clearly need to be more definitively addressed in a future categorical trial, which would be the logical positive outcome of this pilot study.
- Conditions
- RECURRENT GLIOBLASTOMA, Brain Tumor
- Being tested
- Optune(NOVOTTF-100A)
- Keywords
- RECURRENT GLIOBLASTOMA, Brain Tumor
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Optune(NOVOTTF-100A)Device
| Study group | Role | What they receive |
|---|---|---|
| Optune+RT+Bevacuzimab | Other | Part 1:
Bevacizumab every 2 weeks plus Optune daily for 4 week cycles.
Part 2:
RT will begin post 3 round of Bevacizumab (hypofractionated radiotherapy: 30 Gy in 5 fractions or 35 Gy in 10 fractions) per physician choice.
Part 3:
Adjuvant Bevacizumab and Optune Receives: Device: Optune(NOVOTTF-100A) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a Grade 3 or High Toxicity/Adverse Event (Primary Measure)
The ability to complete protocol treatment (i.e. tri-modality treatment) without undue acute toxicity as defined below
- : <40% rate of Grade 3 or higher nonhematologic toxicity.
- : <15% rate of Grade 4 or higher nonhematologic toxicity
- : <5% rate of Grade 4+ scalp dermatitis
- : <50% rate of Grade 2-3 scalp dermatitis
Early stopping rules: Two or more Grade 2 or higher symptomatic CNS hemorrhages; Eight treatment-related Grade 3 or higher non hematologic or Grade 4 or higher hematologic toxicities.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2013 (estimated)
- Study startMay 2014
- Primary completionAug 2019
- Study completionAug 2019
Why it stopped: Poor accrual
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 RECURRENT GLIOBLASTOMAStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- NovoCure Ltd.
- Responsible party
- Principal investigator, Department of Radiation Oncology, University of Maryland, Baltimore
- Investigators
- Kwok Young, MD, Principal investigator, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01925573
- Sponsor's protocol ID
- HP-00056719
- Status last verified
- Jan 2022
- First submitted
- 13 Aug 2013
- Last updated
- 3 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proposed Pilot Study of Combined Optune+ Bevacizumab, and Hypofractionated Stereotactic Irradiation for Bevacizumab-Naive Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT01925573
- Acronym / sponsor ID
- HP-00056719
- Conditions
- RECURRENT GLIOBLASTOMA, Brain Tumor
- Keywords
- RECURRENT GLIOBLASTOMA, Brain Tumor
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- NovoCure Ltd.
- Study start
- May 2014 (actual)
- Primary completion
- Aug 2019 (actual)
- Study completion
- Aug 2019 (actual)
- First posted
- 19 Aug 2013 (estimated)
- Results
- Posted 3 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This protocol is designed to generate and provide preliminary data to determine the safety and activity of combination therapy using tumor treating fields (TTFields; Optune(NovoTTF-100A); Novocure, Haifa, Israel), a novel FDA-approved therapy utilizing alternating electric fields to inhibit tumor cell growth, along with bevacizumab (Avastin; Genentech, San Francisco, CA), a humanized monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), and hypofractionated stereotactic radiotherapy, a highly-focal abbreviated course of brain irradiation, in the treatment of patients with bevacizumab-naive recurrent GBM. Each of these individual therapies, and also several combinations in doublets, has already demonstrated safety and efficacy but prospective clinical data for the concurrent combination of all three therapies are lacking.
Detailed description
The combination of Optune(NovoTTF) with the active regimen of bevacizumab and hypofractionated stereotactic radiotherapy bases the addition of an effective new treatment in the setting of a safe regimen with favorable survival reports. To date, no clinical data are available on the interaction of concomitant tumor treating fields with radiation therapy either with or without bevacizumab. TTF and radiation both have the potential to enhance the other's therapeutic ratio though synergistic mechanisms of action. The addition of bevacizumab to this regimen has both therapeutic and improved-toxicity implications. A trial combining Optune with the proven regimen of HFSRT and bevacizumab for recurrent glioblastoma affords an avenue to demonstrate safety in a population who may more readily derive a benefit from novel multimodality therapy and explore the potential for synergistic effect. The endpoint of efficacy would clearly need to be more definitively addressed in a future categorical trial, which would be the logical positive outcome of this pilot study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Optune+RT+Bevacuzimab | Other | Device: Optune(NOVOTTF-100A)Part 1: Bevacizumab every 2 weeks plus Optune daily for 4 week cycles. Part 2: RT will begin post 3 round of Bevacizumab (hypofractionated radiotherapy: 30 Gy in 5 fractions or 35 Gy in 10 fractions) per physician choice. Part 3: Adjuvant Bevacizumab and Optune |
Who may qualify
- Ages
- 22 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 1 Patients with recurrent or progressive glioblastoma or other grade IV malignant glioma (i.e. glioblastoma, gliosarcoma, giant cell glioblastoma, etc.) who have failed prior radiation but who have not progressed/recurred on bevacizumab. Patients will be eligible if the original histology was lower-grade glioma and subsequent diagnosis of glioblastoma or gliosarcoma is made.
- 2 Patients with any number of recurrences are allowed. 3 Brain MRI demonstrates an enhancing tumor < 8 cm in largest diameter. 4 Karnofsky performance status ≥ 70%. 5 Age ≥ 22 years old. 6 Patients must have the following laboratory values:
- 9 Minimum interval since last major surgery, open biopsy, or significant traumatic injury is 4 weeks 10 Minimum interval since last drug therapy:
- 12 Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Female patients of child-bearing potential must have a negative pregnancy test.
- 13 Patients with history of prior invasive malignancy (except non-melanomatous skin cancer) must have been disease free for a minimum of 1 year.
Key exclusion criteria (9 listed)
- 1 Any prior therapy with bevacizumab 2 Any significant hemorrhage defined as > 1 cm diameter of blood seen on the MRI or CT scan. If > 1 cm of acute blood is detected, the patient will be ineligible for this trial.
- 3 Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury.
- 4 Patients with impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- 7 Implanted pacemaker, defibrillator or deep brain stimulator, other implanted electronic devices in the brain or documented clinically significant arrhythmias.
- 8 Infra-tentorial tumor. 9 Known sensitivity to conductive hydrogels. 10 Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory).
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 |
|---|---|---|
| Optune(NOVOTTF-100A) | Device | Optune+RT+Bevacuzimab |
Primary outcome
Number of Participants With a Grade 3 or High Toxicity/Adverse Event (Primary Measure)
Time frame: 6 months
The ability to complete protocol treatment (i.e. tri-modality treatment) without undue acute toxicity as defined below * : <40% rate of Grade 3 or higher nonhematologic toxicity. * : <15% rate of Grade 4 or higher nonhematologic toxicity * : <5% rate of Grade 4+ scalp dermatitis * : <50% rate of Grade 2-3 scalp dermatitis Early stopping rules: Two or more Grade 2 or higher symptomatic CNS hemorrhages; Eight treatment-related Grade 3 or higher non hematologic or Grade 4 or higher hematologic toxicities.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Kwok Young, MD principal investigator
University of Maryland, Baltimore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Optune(NOVOTTF-100A) in people with RECURRENT GLIOBLASTOMA and Brain Tumor, run by University of Maryland, Baltimore at 1 site 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 17 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 3 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Feb 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?
Number of Participants With a Grade 3 or High Toxicity/Adverse Event (Primary Measure) (time frame: 6 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 3 Feb 2022.