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

NCT02348255 | Withdrawn Phase 2 DMC

• 4 other identifiers: UCDCC#249663113P30CA093373NCI-2014-02628
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Adult Brain Glioblastoma; Recurrent Adult Brain Neoplasm

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (1)

Treatment (bevacizumab, carmustine, NovoTTF-100A)

EXPERIMENTAL

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.

Procedure: Electric Field Therapy; Biological: Bevacizumab; Drug: Carmustine; Other: Quality-of-Life Assessment

Interventions

Electric Field Therapy PROCEDURE

Undergo NovoTTF-100A

Treatment (bevacizumab, carmustine, NovoTTF-100A)

Bevacizumab BIOLOGICAL

Given IV

Also known as: Avastin, rhuMab-VEGF

Treatment (bevacizumab, carmustine, NovoTTF-100A)

Carmustine DRUG

Given IV

Also known as: FDA 0345

Treatment (bevacizumab, carmustine, NovoTTF-100A)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (bevacizumab, carmustine, NovoTTF-100A)

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Davis: lead
• National Cancer Institute (NCI): collaborator
• NovoCure Ltd.: collaborator

Study Sites (2)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Piedmont Hospital

Atlanta, Georgia, 30309, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Bevacizumab; Carmustine

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Study Officials

• Robert O'Donnell

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2015
• First Posted: January 28, 2015
• Study Start: January 1, 2016
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: January 9, 2018

Record last verified: 2018-01

Locations

US (2)