Tumor Treating Fields With Chemoradiation in Newly Diagnosed GBM

Study Overview
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Brief Summary
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The study is an open-label pilot study in newly diagnosed glioblastoma patients following surgery. Eligible patients will receive treatment with tumor treating fields therapy using the Optune device starting less than 2 weeks prior to start of chemoradiation. Patients will receive radiation and temozolomide at a routine treatment dose and schedule.

Detailed Description
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The study is an open-label pilot study in newly diagnosed glioblastoma patients following surgery. Eligible patients will receive treatment with tumor treating fields therapy using the Optune device starting less than 2 weeks prior to start of chemoradiation. Patients will receive radiation and temozolomide at a routine treatment dose and schedule. The expected toxicity is skin related, and patients will be followed closely with weekly skin and neurological examinations during radiation therapy and for 8 weeks afterwards to capture any delayed toxicity as they begin adjuvant therapy per routine treatment. As long as study treatment is tolerated and their conditions remain stable, patients will continue the treatment for up to 24 months. Prior to enrollment, an exploratory analysis of radiation dosimetry will be performed by phantom modeling incorporating the Optune arrays. The study incorporates three stages of recruitment to confirm the safety of combining tumor treating fields therapy with concurrent chemoradiation: a safety lead-in cohort of the first 6 patients enrolled, a second safety lead-in cohort of 9 patients, and an expansion cohort with 15 additional patients.

Official Title
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Safety and Tolerability of Tumor Treating Fields (TTFields) Combined With Chemoradiation in Newly Diagnosed Glioblastoma (Unity)

Conditions
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Glioblastoma, Cancer of Brain, Glioblastoma Multiforme, Brain Tumor

Intervention / Treatment
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* Device: Tumor Treating Fields
* Drug: Temozolomide
* Radiation: Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: GBM or Gliosarcoma by histology MGMT methylation status and IDH mutation status must be assessed at the study site or patient's referral center. MGMT status will be used for stratification purposes but will not exclude patients from this study if they are either methylated, unmethylated, or indeterminate, or in process at the time of enrollment. Similarly, subjects with tumors that are IDH mutated or wild type are both eligible. Supratentorial location Maximum safe resection (including patients who can only safely be biopsied) 22 years of age or older Estimated survival of at least 12 weeks KPS 70% or greater at time of entry to study Patient provided written informed consent, or provided by a legally authorized representative Willingness to comply with all procedures, including visits or evaluations, imaging, laboratory tests and rescue measures Acceptable method of birth control (see appendix) Have had a contrast-enhanced brain MRI after tumor resection procedure. If biopsy alone performed, cranial CT may be used in place of MRI, only if the patient had a preoperative MRI scan within 14 days of the biopsy. The following time period must have elapsed prior to study enrollment: 3-6 weeks (21-42 days) from time of definitive surgery or 2-4 weeks (14-28 days) from the time of biopsy, for those who were only able to safely have a biopsy and not full resection. Exclusion Criteria: Craniotomy or stereotactic biopsy wound dehiscence or infection Known by history to be HIV positive or to have an AIDS-related illness, active Hepatitis B, or active Hepatitis C (testing not required) Presence of skull defects (bullets, metal fragments, missing bone) Patients with implanted electronic medical devices (including but not limited to: pacemaker, vagal nerve stimulator, or pain stimulator) Prior invasive malignancy, unless disease free for 3 or more years, with the exception of basal cell carcinoma, cervical carcinoma in situ, or melanoma in situ Recurrent malignant gliomas or higher grade gliomas transformed from previous low grade (II) glioma Patients with any current Primary brain stem or spinal cord tumor Prior use of temozolomide Prior treatment with Avastin Individuals requiring >8mg of dexamethasone per day within 7 days prior to Day 1 (high dose steroid taper following craniotomy with >8mg of dexamethasone is allowed during the screening period, but subjects must taper down to 8mg or less of dexamethasone (or bioequivalent) within 7 days prior to Day 1). Clinically significant lab abnormalities at screening showing bone marrow, hepatic, and renal dysfunction: Thrombocytopenia (platelet count < 100 x 103/μL) Neutropenia (absolute neutrophil count < 1.5 x 103/μL) Significant liver function impairment - AST or ALT > 3 times the upper limit of normal Total bilirubin > upper limit of normal Significant renal impairment (serum creatinine > 1.7 mg/dL) CTC grade 4 non-hematological Toxicity (except for alopecia, nausea, vomiting) at screening Inability to swallow pills Clinically significant or unstable comorbid medical condition, per investigator discretion (for example, active or uncontrolled infection requiring systemic therapy, including known HIV or hepatitis B or C virus) Known current alcohol or drug abuse, per investigator discretion. Prior history of substance abuse is permissible if subject has been sober for the past 3 years. Any clinically significant psychiatric condition that would prohibit patient willingness or ability to successfully complete study procedures, per investigator discretion Patients with an allergy to or an inability to have gadolinium contrast dye administered with MRI Patients with aneurysm clips or implanted metal objects in the brain Patients with significant skin breakdown on the scalp Patients who cannot receive standard of care radiation therapy and can only receive hypofractionated radiation due to age and poor performance status , per investigator discretion

Ages Eligible for Study
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Minimum Age: 22 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: Sequential Assignment
Interventional Model Description: The study is an open-label pilot study. Following surgery, eligible patients will start tumor treating fields therapy with the Optune device less than 2 weeks prior to radiation and temozolomide given at a dose and schedule conforming to routine treatment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Patients will receive trimodal therapy consisting of tumor treating fields therapy with the Optune device concurrent with temozolomide and radiation therapy. | Device: Tumor Treating Fields<br>* Optune is intended as a treatment for adult patients (22 years of age or older) with histologically-confirmed glioblastoma multiforme (GBM). Treatment will begin approximately 1 week prior to start of radiation and temozolomide treatment and continue concurrently throughout the duration of the study.<br>* Other names: Novocure;Drug: Temozolomide<br>* Patients will be given temozolomide according to routine treatment dosing and schedule.<br>* Other names: Temodar;Radiation: Radiation Therapy<br>* Patients will be given radiation therapy according to routine treatment dosing and schedule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of treatment-related adverse events associated with trimodal therapy | Number of patients who experienced a treatment-related adverse event | 15 weeks (8 weeks after completion of trimodal therapy) | 
| Severity of treatment-related adverse events associated with trimodal therapy | Number of patients who experienced a treatment-related serious adverse event based on the NCI Common Terminology Criteria for Adverse Events (version 4.03) | 15 weeks (8 weeks after completion of trimodal therapy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival at 6 months and 24 months | Number of patients who are progression free at 6 months and 24 months | 24 months | 
| Overall Survival Rate | Number of patients alive at 24 months | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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temozolomide, tumor treating fields, optune, novocure, glioblastoma, brain tumor