Adult Giant Cell GlioblastomaPhase 2NCT01894061
NovoTTF-100A With Bevacizumab (Avastin) in Patients With Recurrent Glioblastoma
A Phase 2 study testing Bevacizumab, NovoTTF-l00A and Quality of Life Assessment in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by Case Comprehensive Cancer Center at 3 sites in United States.
Trial summary
NovoTTF-100A is a device and Bevacizumab is a study drug that have both been approved by the FDA (Food and Drug Administration) for use as monotherapy in treating glioblastoma multiforme. Read more about this study
- Who is it for?
- Ages 22 years and older
- Conditions the study is for
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
- What is being tested?
- Bevacizumab, NovoTTF-l00A and Quality of Life Assessment
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 3 sitesUnited States
- Study dates
- 18 Sep 2013to 1 Jul 2019
- 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
- Patients with histologically confirmed glioblastoma or other grade IV malignant glioma (i.e. gliosarcoma, small cell glioblastoma, etc.), recurrent after prior external-beam fractionated radiotherapy and temozolomide chemotherapy.
- Patients with up to two prior recurrences are allowed.
- Karnofsky performance status ≥70.
- Patients must have the following laboratory values:
- Absolute neutrophil count (ANC) ≥1.5 x 10^9/L
- Platelets ≥ 100 x 10^9/L
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- Hemoglobin (Hgb) > 9 g/dL
- Serum total bilirubin: ≤ 1.5 x ULN
- ALT and AST ≤ 3.0 x ULN
- Serum creatinine ≤ 1.5 x ULN
- Blood coagulation parameters: INR ≤ 1.5
- Minimum interval since completion of radiation treatment is 12 weeks
- 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.
- Patients must have signed an approved informed consent and authorization permitting release of personal health information.
- Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. The effects of bevacizumab on developing fetus or nursing infant are not known. Female patients of child-bearing potential must have a negative pregnancy test.
- Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission. Patients with other prior malignancies must be disease-free for ≥ three years.
- 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.
Who cannot join
- Patients who have had previous treatment with bevacizumab, and or NovoTTF 100A system.
- 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
- 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 systolic blood pressure (SBP) ≥ 160 mm Hg or diastolic blood pressure (DBP) ≥ 100 mm Hg while on anti-hypertensive medications)
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- Patients with cirrhosis, or active viral or nonviral hepatitis.
- Implanted pacemaker, defibrillator or deep brain stimulator, other implanted electronic devices in the brain or documented clinically significant arrhythmias.
- Infra-tentorial tumor
- Evidence of increased intracranial pressure (clinically significant papilledema, vomiting and nausea or reduced level of consciousness)
- Known sensitivity to conductive hydrogels
- Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
- 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
- Pregnant or breast-feeding women
- Patients unwilling or unable to comply with the protocol
- Patients with leptomeningeal disease
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Cincinnati
Cincinnati, Ohio, 45220
University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: A Prospective Phase II Trial of NovoTTF-100A With Bevacizumab (Avastin) in Patients With Recurrent Glioblastoma
NovoTTF-100A is a device and Bevacizumab is a study drug that have both been approved by the FDA (Food and Drug Administration) for use as monotherapy in treating glioblastoma multiforme. The NovoTTF-l00A is a portable battery operated device which produces TTFields within the human body using surface electrodes (transducer arrays). Intermediate frequency electric fields (TTFields) stunt the growth of tumor cells.
The purpose of this study is to determine the efficacy of the combination of Bevacizumab and NovoTTF-100A in Bevacizumab naive (meaning have never received bevacizumab before) patients with recurrent glioblastoma (GBM) as measured by 6-month progression free survival.
Read the detailed description
This will be an open label Phase II trial in adults with recurrent glioblastoma (GBM). The NovoTTF-100A treatment and Bevacizumab will be administered on an outpatient basis; NovoTTF-100A treatment will be initiated in the outpatient clinic.
PRIMARY OBJECTIVES:
- To determine the efficacy of the combination of bevacizumab and NovoTTF-100A in bevacizumab-naive patients with recurrent glioblastoma (GBM) as measured by 6-month progression-free survival (PFS6).
SECONDARY OBJECTIVES:
- To assess safety and tolerability of the combination of bevacizumab and Novo-TTF-100A in this patient population.
II. To evaluate overall survival in this population. III. To determine objective response rate (ORR) by modified Revised Assessment in Neuro-Oncology (RANO) criteria in this population.
IV. To assess time-to-progression in this population. V. To assess neurocognitive function (NCF) and quality of life (QOL) in this population.
OUTLINE:
Patients receive bevacizumab intravenously (IV) on days 1 and 15. Patients also undergo electric field therapy with NovoTTF-100A for at least 18 hours daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for at least 28 days.
- Conditions
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
- Being tested
- Bevacizumab, NovoTTF-l00A, Quality of Life Assessment
- Keywords
- adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, recurrent adult brain tumor, Bevacizumab-naive, NovoTTF-100A
- Medical subject headings
- Glioblastoma, Gliosarcoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabBiological
Also called Avastin, anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, anti-VEGF rhuMAb
Bevacizumab will be administered intravenously on days 1 and 15 of each 28 day cycle. The dose of bevacizumab will be 10 mg/kg of actual body weight.
NovoTTF-l00ADevice
Also called electric field therapy
NovoTTF-100A will be worn continuously.
Quality of Life AssessmentOther
Also called FACT-Br questionnaire
Functional Assessment of Cancer Therapy including Brain Tumor module (FACT-Br) questionnaire
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab and NovoTTF-100A | Experimental | Bevacizumab will be administered intravenously on days 1 and 15 of each 28 day cycle.The dose of bevacizumab will be 10 mg/kg of actual body weight. Receives: Biological: Bevacizumab; Device: NovoTTF-l00A; Other: Quality of Life Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of Participants With 6-month Progression-free Survival (PFS6)
Efficacy of therapy as measured by percent of participants with (PFS6). This trial will be considered successful if at least 20% of participants achieve PFS at 6 months. Disease progression is defined by RANO criteria. In cases where the RANO criteria cannot be applied, progression should be based on unequivocal evidence of progressive disease sufficient to require a change in therapy. The Modified RANO criteria are a set of guidelines for evaluating treatment response clinical trials. Modified RANO Response Criteria include levels of response including Complete Response (CR), Partial Response (PR), Minor Response (MR), Stable Disease (SD), or Progressive Disease.
Measured: 6 months
Secondary outcomes (7)
Objective Response Rate (ORR) Based on RANO Criteria
ORR as defined by the modified Response Assessment in Neuro-Oncology (RANO) criteria.
Measured: 30 days after treatment completion through study completion, an average of 5 years, 9 months
Number of Participants Experiencing Grade 3/4 Toxicities Related to Therapy Combination Per by CTCAE Version 4.0.
Number of participants experiencing grade 3 or 4 toxicities related to therapy combination per by CTCAE version 4.0.
Measured: 5 years, 9 months
Median Overall Survival
Median overall survival (OS) in months
Measured: 30 days after treatment completion (Treatment continued until disease progression in the brain, death, or unacceptable side effects to patient)
Median Time-to-progression
Median time to progression by Kaplan Meier methodology. Disease progression is defined by RANO criteria. In cases where the RANO criteria cannot be applied, progression should be based on unequivocal evidence of progressive disease sufficient to require a change in therapy. The Modified RANO criteria are a set of guidelines for evaluating treatment response clinical trials. Modified RANO Response Criteria include levels of response including Complete Response (CR), Partial Response (PR), Minor Response (MR), Stable Disease (SD), or Progressive Disease.
Measured: 30 days after treatment completion (Treatment continued until disease progression in the brain, death, or unacceptable side effects to patient)
Time to Reliable Change in Neurocognitive Function (NCF)
Time to reliable change in NCF by Kaplan Meier methodology. Memory, verbal fluency, visual-motor speed, executive function and motor dexterity tests will be administered. NCF testing involves standardized psychometric instruments that are sensitive to the neurotoxic effects of cancer treatment in brain tumor clinical trials.
Measured: 30 days after treatment completion (Treatment continued until disease progression in the brain, death, or unacceptable side effects to patient)
Change From Baseline in Quality of Life (QOL) as Measured by FACT-BR Score
Functional Assessment of Cancer Therapy including Brain Tumor module (FACT-Br) is a 54-item questionnaire that has four areas of cumulative measurements (physical well-being, social/family well-being, emotional well-being and functional well-being) with a scale of 0-4. The FACT-Br total score ranges between 0 and 76. The higher the score, the better the quality of life.
Measured: Baseline, 30 days after treatment completion (Treatment continued until disease progression in the brain, death, or unacceptable side effects to patient)
Percent of Participants With 12-month Progression-free Survival
Efficacy of therapy as measured by percent of participants with 12-month PFS. Disease progression is defined by modified RANO criteria. In cases where the modified RANO criteria cannot be applied, progression should be based on unequivocal evidence of progressive disease sufficient to require a change in therapy. The Modified RANO criteria are a set of guidelines for evaluating treatment response clinical trials. Modified RANO Response Criteria include levels of response including Complete Response (CR), Partial Response (PR), Minor Response (MR), Stable Disease (SD), or Progressive Disease.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2013 (estimated)
- Study start18 Sep 2013
- Primary completion1 Jul 2019
- Study completion1 Jul 2019
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 Adult Giant Cell GlioblastomaStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe 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
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- NovoCure Ltd.
- Responsible party
- Sponsor
- Investigators
- David Peereboom, MD, Principal investigator, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01894061
- Sponsor's protocol ID
- CASE3313
- Status last verified
- Feb 2025
- First submitted
- 3 Jul 2013
- Last updated
- 17 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Phase II Trial of NovoTTF-100A With Bevacizumab (Avastin) in Patients With Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT01894061
- Acronym / sponsor ID
- CASE3313
- Conditions
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
- Keywords
- adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, recurrent adult brain tumor, Bevacizumab-naive, NovoTTF-100A
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- NovoCure Ltd.
- Study start
- 18 Sep 2013 (actual)
- Primary completion
- 1 Jul 2019 (actual)
- Study completion
- 1 Jul 2019 (actual)
- First posted
- 9 Jul 2013 (estimated)
- Results
- Posted 17 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
NovoTTF-100A is a device and Bevacizumab is a study drug that have both been approved by the FDA (Food and Drug Administration) for use as monotherapy in treating glioblastoma multiforme. The NovoTTF-l00A is a portable battery operated device which produces TTFields within the human body using surface electrodes (transducer arrays). Intermediate frequency electric fields (TTFields) stunt the growth of tumor cells.
The purpose of this study is to determine the efficacy of the combination of Bevacizumab and NovoTTF-100A in Bevacizumab naive (meaning have never received bevacizumab before) patients with recurrent glioblastoma (GBM) as measured by 6-month progression free survival.
Detailed description
This will be an open label Phase II trial in adults with recurrent glioblastoma (GBM). The NovoTTF-100A treatment and Bevacizumab will be administered on an outpatient basis; NovoTTF-100A treatment will be initiated in the outpatient clinic.
PRIMARY OBJECTIVES:
- To determine the efficacy of the combination of bevacizumab and NovoTTF-100A in bevacizumab-naive patients with recurrent glioblastoma (GBM) as measured by 6-month progression-free survival (PFS6).
SECONDARY OBJECTIVES:
- To assess safety and tolerability of the combination of bevacizumab and Novo-TTF-100A in this patient population.
II. To evaluate overall survival in this population. III. To determine objective response rate (ORR) by modified Revised Assessment in Neuro-Oncology (RANO) criteria in this population.
IV. To assess time-to-progression in this population. V. To assess neurocognitive function (NCF) and quality of life (QOL) in this population.
OUTLINE:
Patients receive bevacizumab intravenously (IV) on days 1 and 15. Patients also undergo electric field therapy with NovoTTF-100A for at least 18 hours daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for at least 28 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab and NovoTTF-100A | Experimental | Biological: Bevacizumab, Device: NovoTTF-l00A, Other: Quality of Life AssessmentBevacizumab will be administered intravenously on days 1 and 15 of each 28 day cycle.The dose of bevacizumab will be 10 mg/kg of actual body weight. |
Who may qualify
- Ages
- 22 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patients with histologically confirmed glioblastoma or other grade IV malignant glioma (i.e. gliosarcoma, small cell glioblastoma, etc.), recurrent after prior external-beam fractionated radiotherapy and temozolomide chemotherapy.
- Patients with up to two prior recurrences are allowed.
- Karnofsky performance status ≥70.
- Patients must have the following laboratory values:
- Minimum interval since completion of radiation treatment is 12 weeks
Key exclusion criteria (16 listed)
- Patients who have had previous treatment with bevacizumab, and or NovoTTF 100A system.
- 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
- Patients with impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- Patients with cirrhosis, or active viral or nonviral hepatitis.
- Implanted pacemaker, defibrillator or deep brain stimulator, other implanted electronic devices in the brain or documented clinically significant arrhythmias.
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: Avastin, anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, anti-VEGF rhuMAbBevacizumab will be administered intravenously on days 1 and 15 of each 28 day cycle. The dose of bevacizumab will be 10 mg/kg of actual body weight. | Biological | Bevacizumab and NovoTTF-100A |
| NovoTTF-l00AAlso: electric field therapyNovoTTF-100A will be worn continuously. | Device | Bevacizumab and NovoTTF-100A |
| Quality of Life AssessmentAlso: FACT-Br questionnaireFunctional Assessment of Cancer Therapy including Brain Tumor module (FACT-Br) questionnaire | Other | Bevacizumab and NovoTTF-100A |
Primary outcome
Percent of Participants With 6-month Progression-free Survival (PFS6)
Time frame: 6 months
Efficacy of therapy as measured by percent of participants with (PFS6). This trial will be considered successful if at least 20% of participants achieve PFS at 6 months. Disease progression is defined by RANO criteria. In cases where the RANO criteria cannot be applied, progression should be based on unequivocal evidence of progressive disease sufficient to require a change in therapy. The Modified RANO criteria are a set of guidelines for evaluating treatment response clinical trials. Modified RANO Response Criteria include levels of response including Complete Response (CR), Partial Response (PR), Minor Response (MR), Stable Disease (SD), or Progressive Disease.
7 secondary outcomes
Objective Response Rate (ORR) Based on RANO Criteria
Time frame: 30 days after treatment completion through study completion, an average of 5 years, 9 months
Number of Participants Experiencing Grade 3/4 Toxicities Related to Therapy Combination Per by CTCAE Version 4.0.
Time frame: 5 years, 9 months
Median Overall Survival
Time frame: 30 days after treatment completion (Treatment continued until disease progression in the brain, death, or unacceptable side effects to patient)
Median Time-to-progression
Time frame: 30 days after treatment completion (Treatment continued until disease progression in the brain, death, or unacceptable side effects to patient)
Time to Reliable Change in Neurocognitive Function (NCF)
Time frame: 30 days after treatment completion (Treatment continued until disease progression in the brain, death, or unacceptable side effects to patient)
Change From Baseline in Quality of Life (QOL) as Measured by FACT-BR Score
Time frame: Baseline, 30 days after treatment completion (Treatment continued until disease progression in the brain, death, or unacceptable side effects to patient)
Percent of Participants With 12-month Progression-free Survival
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma
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 Peereboom, MD principal investigator
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
3 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, NovoTTF-l00A and Quality of Life Assessment in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by Case Comprehensive Cancer Center at 3 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 20 inclusion and 16 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: finished, as of the sponsor's last update on 17 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 17 Feb 2025). 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?
Percent of Participants With 6-month Progression-free Survival (PFS6) (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 17 Feb 2025.