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

Phase 2

Withdrawn

• Conditions: Recurrent Adult Brain Neoplasm; Adult Brain Glioblastoma
• Interventions: Procedure: Electric Field Therapy; Biological: Bevacizumab; Drug: Carmustine; Other: Quality-of-Life Assessment

• Registration Number: NCT02348255
• Lead Sponsor: University of California, Davis

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 mult...

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).
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Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2015-01-22
• Study First Submitted QC: 2015-01-27
• Study First Posted: 2015-01-28
• Study Start: 2016-01
• Primary Completion: 2017-01
• Study Completion: 2017-01
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-05
• Last Update Posted: 2018-01-09

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (bevacizumab, carmustine, NovoTTF-100A)	Electric Field Therapy	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.
Treatment (bevacizumab, carmustine, NovoTTF-100A)	Bevacizumab	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.
Treatment (bevacizumab, carmustine, NovoTTF-100A)	Quality-of-Life Assessment	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.
Treatment (bevacizumab, carmustine, NovoTTF-100A)	Carmustine	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.

Primary Outcome Measures

Name	Time	Method
Overall Survival	Time from first day of treatment to time of death due to any cause, assessed up to 6 months	Will be estimated using the product-limit method of Kaplan and Meier.
Change in tumor volume using magnetic resonance imaging (MRI)	Baseline to day 168	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	Baseline to day 168	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.
Incidence of adverse events, assessed by National Cancer Institute-Common Terminology Criteria 4.0 toxicity criteria	Up to 12 months	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.
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	Up to 6 months
Progression Free Survival	Time from first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 6 months	Will be estimated using the product-limit method of Kaplan and Meier.

Trial Locations

Locations (2)

University of California Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

Piedmont Hospital; 🇺🇸 Atlanta, Georgia, United States