Clinical trial NCT02348255: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Adult Brain Glioblastoma
Recurrent Adult Brain Neoplasm
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: NovoCure Ltd.
First posted: 2015-01-28
Enrollment: 0
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of adverse events, assessed by National Cancer Institute-Common Terminology Criteria 4.0 toxicity criteria
timeFrame: Up to 12 months
measure: Progression Free Survival
timeFrame: Time from first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 6 months
measure: Overall Survival
timeFrame: Time from first day of treatment to time of death due to any cause, assessed up to 6 months
measure: 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
timeFrame: Up to 6 months
measure: Change in tumor volume using magnetic resonance imaging (MRI)
timeFrame: Baseline to day 168
measure: Change in linear dimension using MRI
timeFrame: Baseline to day 168
Secondary outcomes:
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
Study officials:
affiliation: University of California, Davis
name: Robert O'Donnell
role: PRINCIPAL_INVESTIGATOR
References: