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

A Phase II, Multi-institutional Trial of NOVO-TTF-100A, BCNU and Bevacizumab for GBM in First Relapse

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.

Study Overview

• Status: Withdrawn
• Conditions: Recurrent Adult Brain Neoplasm; Adult Brain Glioblastoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Biological: Bevacizumab; Drug: Carmustine; Procedure: Electric Field Therapy

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (bevacizumab, carmustine, NovoTTF-100A); 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.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Biological: Bevacizumab; Given IV; Other Names: Avastin; rhuMab-VEGF; Drug: Carmustine; Given IV; Other Names: FDA 0345; Procedure: Electric Field Therapy; Undergo NovoTTF-100A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 12 months
Progression Free Survival	Will be estimated using the product-limit method of Kaplan and Meier.	Time from first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 6 months
Overall Survival	Will be estimated using the product-limit method of Kaplan and Meier.	Time from first day of treatment to time of death due to any cause, assessed up to 6 months
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
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.	Baseline to day 168
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.	Baseline to day 168

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: National Cancer Institute (NCI); NovoCure Ltd.
• Investigators: Principal Investigator: Robert O'Donnell, University of California, Davis

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: January 22, 2015
• First Submitted That Met QC Criteria: January 27, 2015
• First Posted (Estimate): January 28, 2015

Study Record Updates

• Last Update Posted (Actual): January 9, 2018
• Last Update Submitted That Met QC Criteria: January 5, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Glioblastoma; Brain Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Carmustine
• Other Study ID Numbers: UCDCC#249 (Other Identifier: University of California Davis Comprehensive Cancer Center); P30CA093373 (U.S. NIH Grant/Contract); 663113 (Other Identifier: UC Davis); NCI-2014-02628 (Registry Identifier: CTRP (Clinical Trial Reporting Program))