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NovoTTF-100A With Bevacizumab and Carmustine in Treating Patients With Glioblastoma Multiforme in First Relapse

Primary Purpose

Adult Brain Glioblastoma, Recurrent Adult Brain Neoplasm

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Electric Field Therapy
Bevacizumab
Carmustine
Quality-of-Life Assessment
Sponsored by
University of California, Davis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Brain Glioblastoma

Eligibility Criteria

22 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed GBM
  • Progressive disease after temozolomide and radiation therapy (in "first relapse")
  • At least 28 days since chemotherapy or radiation
  • Karnofsky performance score at least 70%
  • Platelet count >= 130/mm^3
  • Absolute neutrophil count >= 1500/mm^3
  • Calculated creatinine clearance greater than 45 mg/dl using the Cockcroft-Gault formula
  • Aspartate aminotransferase (AST) < 2 times the upper limit of normal
  • Bilirubin < 1.5 times the upper limit of normal
  • Subjects with child-bearing potential agree to use effective means of contraception

Exclusion Criteria:

  • Prior systemically administered nitrosoureas or vascular endothelial growth factor (VEGF) targeted therapy
  • Chemotherapy for glioma other than temozolomide or Gliadel wafers (steroids are allowed)
  • Pregnant or breast feeding
  • Active inflammatory bowel disease
  • Abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months
  • Hypertension: systolic blood pressure (SBP) > 150 or diastolic blood pressure (DBP) > 100 mm mercury (Hg) despite antihypertensive medications
  • New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF); myocardial infarction or unstable angina within 6 months
  • History of thrombosis
  • Symptomatic peripheral vascular disease, stroke or transient ischemic attack within 6 months
  • Bleeding risks: Required to be on therapeutic anticoagulation (aspirin is allowed), coagulopathy (e.g. hemophilia or von Willebrand's disease); any grade III or greater hemorrhage, major surgical procedure, or significant trauma within 28 days; core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days
  • Activated partial thromboplastin time (APTT) must not exceed 32.5 seconds (normal range 21.8-31.5 seconds); international normalized ratio (INR) must not exceed 1.30 (normal range 0.87-1.18)
  • Serious, non-healing wound, ulcer, or bone fracture
  • Active implanted medical device (e.g. deep brain stimulators, spinal cord stimulators, vagus nerve stimulators, pacemakers, defibrillators, and programmable shunts), a skull defect (such as missing bone with no replacement), a shunt, or bullet fragments
  • Known sensitivity to conductive hydrogels like the gel used on electrocardiogram (ECG) stickers or transcutaneous electrical nerve stimulation (TENS) electrodes
  • Human immunodeficiency virus (HIV) positive
  • Proteinuria at screening as demonstrated by urine dipstick >= 2+
  • Prior organ transplantation
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), clopidogrel or any other drug whose goal is to inhibit platelet function
  • Unable to give signed informed consent

Sites / Locations

  • University of California Davis Comprehensive Cancer Center
  • Piedmont Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (bevacizumab, carmustine, NovoTTF-100A)

Arm Description

Patients receive bevacizumab IV over 30-90 minutes every 2 weeks beginning on day -7 for up to 13 doses and carmustine IV over 4 hours every 8 weeks beginning on day 1 for up to 3 doses. Patients also undergo NovoTTF-100A according to standard procedures starting one week before the first dose of carmustine.

Outcomes

Primary Outcome Measures

Incidence of adverse events, assessed by National Cancer Institute-Common Terminology Criteria 4.0 toxicity criteria
Toxicity summaries will be provided for all subjects who have received any part of the study treatment. Statistical analysis will include estimates of proportions with each class of toxicity with a 95% confidence interval.
Progression Free Survival
Will be estimated using the product-limit method of Kaplan and Meier.
Overall Survival
Will be estimated using the product-limit method of Kaplan and Meier.
Quality of life as measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and BN-20 brain cancer module
Change in tumor volume using magnetic resonance imaging (MRI)
Mean change in linear dimension will be evaluated for shrinkage using a paired t-test. If the assumption of normality is violated, a signed rank test will be used. The Response Assessment in Neuro-oncology (RANO) criteria will be part of the MRI evaluation.
Change in linear dimension using MRI
Mean change in linear dimension will be evaluated for shrinkage using a paired t-test. If the assumption of normality is violated, a signed rank test will be used. The RANO criteria will be part of the MRI evaluation.

Secondary Outcome Measures

Full Information

First Posted
January 22, 2015
Last Updated
January 5, 2018
Sponsor
University of California, Davis
Collaborators
National Cancer Institute (NCI), NovoCure Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02348255
Brief Title
NovoTTF-100A With Bevacizumab and Carmustine in Treating Patients With Glioblastoma Multiforme in First Relapse
Official Title
A Phase II, Multi-institutional Trial of NOVO-TTF-100A, BCNU and Bevacizumab for GBM in First Relapse
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Withdrawn
Why Stopped
Poor Accrual
Study Start Date
January 2016 (Actual)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Davis
Collaborators
National Cancer Institute (NCI), NovoCure Ltd.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies the safety of NovoTTF-100A in combination with bevacizumab and carmustine and to see how well they work in treating patients with glioblastoma multiforme that has returned for the first time. NovoTTF-100A, a type of electric field therapy, delivers low intensity, alternating "wave-like" electric fields that may interfere with multiplication of the glioblastoma multiforme cells. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carmustine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving NovoTTF-100A together with bevacizumab and carmustine may be an effective treatment for glioblastoma multiforme.
Detailed Description
PRIMARY OBJECTIVES: I. Establish the safety of NovoTTF-100A in combination with bevacizumab and BCNU (carmustine) in glioblastoma multiforme (GBM) patients who have relapsed after chemoradiation therapy (first relapse). II. Determine the 6 month overall survival (OS). III. Determine the 6 month progression free survival (PFS). IV. Evaluate the effect of this therapy regimen on quality-of-life. OUTLINE: Patients receive bevacizumab intravenously (IV) over 30-90 minutes every 2 weeks beginning on day -7 for up to 13 doses and carmustine IV over 4 hours every 8 weeks beginning on day 1 for up to 3 doses. Patients also undergo NovoTTF-100A according to standard procedures starting one week before the first dose of carmustine. After completion of study treatment, patients are followed up for 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Brain Glioblastoma, Recurrent Adult Brain Neoplasm

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (bevacizumab, carmustine, NovoTTF-100A)
Arm Type
Experimental
Arm Description
Patients receive bevacizumab IV over 30-90 minutes every 2 weeks beginning on day -7 for up to 13 doses and carmustine IV over 4 hours every 8 weeks beginning on day 1 for up to 3 doses. Patients also undergo NovoTTF-100A according to standard procedures starting one week before the first dose of carmustine.
Intervention Type
Procedure
Intervention Name(s)
Electric Field Therapy
Intervention Description
Undergo NovoTTF-100A
Intervention Type
Biological
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin, rhuMab-VEGF
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Carmustine
Other Intervention Name(s)
FDA 0345
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Incidence of adverse events, assessed by National Cancer Institute-Common Terminology Criteria 4.0 toxicity criteria
Description
Toxicity summaries will be provided for all subjects who have received any part of the study treatment. Statistical analysis will include estimates of proportions with each class of toxicity with a 95% confidence interval.
Time Frame
Up to 12 months
Title
Progression Free Survival
Description
Will be estimated using the product-limit method of Kaplan and Meier.
Time Frame
Time from first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 6 months
Title
Overall Survival
Description
Will be estimated using the product-limit method of Kaplan and Meier.
Time Frame
Time from first day of treatment to time of death due to any cause, assessed up to 6 months
Title
Quality of life as measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and BN-20 brain cancer module
Time Frame
Up to 6 months
Title
Change in tumor volume using magnetic resonance imaging (MRI)
Description
Mean change in linear dimension will be evaluated for shrinkage using a paired t-test. If the assumption of normality is violated, a signed rank test will be used. The Response Assessment in Neuro-oncology (RANO) criteria will be part of the MRI evaluation.
Time Frame
Baseline to day 168
Title
Change in linear dimension using MRI
Description
Mean change in linear dimension will be evaluated for shrinkage using a paired t-test. If the assumption of normality is violated, a signed rank test will be used. The RANO criteria will be part of the MRI evaluation.
Time Frame
Baseline to day 168

10. Eligibility

Sex
All
Minimum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed GBM Progressive disease after temozolomide and radiation therapy (in "first relapse") At least 28 days since chemotherapy or radiation Karnofsky performance score at least 70% Platelet count >= 130/mm^3 Absolute neutrophil count >= 1500/mm^3 Calculated creatinine clearance greater than 45 mg/dl using the Cockcroft-Gault formula Aspartate aminotransferase (AST) < 2 times the upper limit of normal Bilirubin < 1.5 times the upper limit of normal Subjects with child-bearing potential agree to use effective means of contraception Exclusion Criteria: Prior systemically administered nitrosoureas or vascular endothelial growth factor (VEGF) targeted therapy Chemotherapy for glioma other than temozolomide or Gliadel wafers (steroids are allowed) Pregnant or breast feeding Active inflammatory bowel disease Abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months Hypertension: systolic blood pressure (SBP) > 150 or diastolic blood pressure (DBP) > 100 mm mercury (Hg) despite antihypertensive medications New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF); myocardial infarction or unstable angina within 6 months History of thrombosis Symptomatic peripheral vascular disease, stroke or transient ischemic attack within 6 months Bleeding risks: Required to be on therapeutic anticoagulation (aspirin is allowed), coagulopathy (e.g. hemophilia or von Willebrand's disease); any grade III or greater hemorrhage, major surgical procedure, or significant trauma within 28 days; core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days Activated partial thromboplastin time (APTT) must not exceed 32.5 seconds (normal range 21.8-31.5 seconds); international normalized ratio (INR) must not exceed 1.30 (normal range 0.87-1.18) Serious, non-healing wound, ulcer, or bone fracture Active implanted medical device (e.g. deep brain stimulators, spinal cord stimulators, vagus nerve stimulators, pacemakers, defibrillators, and programmable shunts), a skull defect (such as missing bone with no replacement), a shunt, or bullet fragments Known sensitivity to conductive hydrogels like the gel used on electrocardiogram (ECG) stickers or transcutaneous electrical nerve stimulation (TENS) electrodes Human immunodeficiency virus (HIV) positive Proteinuria at screening as demonstrated by urine dipstick >= 2+ Prior organ transplantation Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), clopidogrel or any other drug whose goal is to inhibit platelet function Unable to give signed informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert O'Donnell
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Piedmont Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States

12. IPD Sharing Statement

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NovoTTF-100A With Bevacizumab and Carmustine in Treating Patients With Glioblastoma Multiforme in First Relapse

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