Temozolomide, Radiation Therapy, and Tumor Treating Fields Therapy in Treating Participants With Glioblastoma

Study Overview
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Brief Summary
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This pilot early phase I trial studies the side effects of temozolomide, radiation therapy, and tumor treating fields therapy using Novo tumor treatment fields (TTF)-200A device in participants with glioblastoma. Drugs used in chemotherapy, such as temozolomide, 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. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. NovoTTF-200A device is a portable device that produces alternating electrical fields that may disrupt growth of cancer cells. Giving temozolomide, radiation therapy, and tumor treating fields therapy using NovoTTF-200A device may work better in treating participants with glioblastoma.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the safety and toxicity of combination chemoradiotherapy with NovoTTF-200A device (Optune) treatment in newly diagnosed glioblastoma. SECONDARY OBJECTIVES: I. To determine the median progression-free survival of patients with newly diagnosed glioblastoma treated with radiotherapy with concurrent and adjuvant temozolomide plus Optune. II. To evaluate the median overall survival, 1-year overall survival, and event-free survival. III. Collect tumor O(6)-Methylguanine-DNA-methyltransferase (MGMT) methylation status and isocitrate dehydrogenase (IDH) mutation status. IV. To evaluate the level of circulating tumor deoxyribonucleic acid (DNA) in glioblastoma patient serum during treatment. V. To evaluate the quality of life of patients treated with radiotherapy with concurrent and adjuvant temozolomide plus Optune.

Official Title
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SPARE-Scalp Preservation and Radiation Plus Alternating Electric Tumor Treatment Field (NovoTTF, Optune) for Patients With Glioblastoma: A Pilot Study

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: Temozolomide
* Radiation: Radiation Therapy
* Device: NovoTTF-200A Device
* Procedure: Tumor Treating Fields Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with pathology confirmed newly diagnosed World Health Organization (WHO) grade IV glioma Karnofsky performance status (KPS) ≥ 60 Patients must have recovered from the effects of surgery per treating physician's judgment; there must be a minimum of 21 days from the day of surgery to the day of protocol treatment; for core or needle biopsy, a minimum of 14 days must have elapsed prior to the day of protocol treatment Absolute neutrophil count (ANC) ≥ 1,000 cells/mm^3 Platelets ≥ 100,000 cells/mm^3 Hemoglobin ≥ 9.0 g/dl Creatinine clearance > 30 mL/min Bilirubin < 2.0 mg/dL Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 x upper limit of normal range Women of childbearing potential must have a negative beta-human chorionic gonadotropin (HCG) pregnancy test documented within 14 days prior to registration Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 4 months after last dose of temozolomide Is able to have magnetic resonance imaging (MRI) with contrast of the brain All subjects must be able to comprehend and sign a written informed consent document. If the subject can comprehend the informed consent but is unable to sign, a LAR may sign the written informed consent document. Exclusion Criteria: Infratentorial disease (defined as glioblastoma [GBM] derived from cerebellum or brainstem) Implanted pacemaker, defibrillator or deep brain stimulator, or documented clinically significant arrhythmias A skull defect (such as, missing bone with no replacement) Women of childbearing potential who are pregnant or breastfeeding Evidence of increased intracranial pressure (midline shift > 5 mm, clinically significant papilledema) Serious medical or psychiatric illness likely to interfere with participation in this clinical study, in the opinion of the investigator Prior radiation treatment to the brain Prior treatment with temozolomide Known hypersensitivity to conductive hydrogels like the gel used on electrocardiogram (ECG) stickers or transcutaneous electrical nerve stimulation (TENS) electrodes Known active collagen vascular disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (temozolomide, radiation, NovoTTF-200A device)<br>Participants receive temozolomide PO QD starting day 1 to the end of radiation therapy and undergo 30 fractions of radiation therapy over 15-20 minutes each, 5 days a week (Monday-Friday) for 6 weeks. Beginning day 1 of radiation therapy, participants undergo tumor treatment fields therapy using NovoTTF-200A device over 18 hours or more daily in the absence of disease progression or unacceptable toxicity. Beginning 28 days after the last dose of radiation therapy, participants receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. | Drug: Temozolomide<br>* Given PO<br>* Other names: Temodar;Radiation: Radiation Therapy<br>* Undergo radiation therapy<br>* Other names: RT;Device: NovoTTF-200A Device<br>* Undergo tumor treatment fields therapy using NovoTTF-200A device<br>* Other names: Optune;Procedure: Tumor Treating Fields Therapy<br>* Undergo tumor treatment fields therapy using NovoTTF-200A device<br>* Other names: Alternating Electric Field Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NovoTTF-200A device discontinuation rate due to skin toxicity | Discontinuation events are defined as the discontinuation of NovoTTF-200A device for > 7 consecutive days due to skin toxicity of grade 3 or higher. For discontinuation rates, the method of Atkinson and Brown will be used to allow for the two-stage design. Descriptive analysis will be performed on the acute toxicity data. | Up to 30 days after finishing chemoradiation treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Will be evaluated using the Kaplan-Meier method. | From enrollment up to 1 year | 
| Overall survival | Will be evaluated using the Kaplan-Meier method. | From enrollment up to 1 year | 
| Event-free survival | Will be evaluated using the Kaplan-Meier method. | From enrollment up to 1 year |