Ketogenic Diet With Radiation and Chemotherapy for Newly Diagnosed Glioblastoma

Study Overview
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Brief Summary
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This study aims to see if reducing blood sugar and increasing ketones (a metabolic product that comes from using fats for energy) can increase survival and enhance the the effects of standard radiation and chemotherapy treatments used to treat glioblastoma multiforme (GBM). These changes occur from use of a ketogenic diet. This research has 2 goals: Show that patients can tolerate the diet and maintain low blood glucose and high blood ketone levels. Show if this diet enhances the effectiveness of standard treatment by prolonging survival of patients with a GBM.

Detailed Description
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The investigators propose to offer this study to patients with newly diagnosed glioblastoma multiforme (GBM) that undergo gross total resection (GTR) or subtotal resection (STR) of their tumor. Post-operatively, these patients and their families will be instructed in the implementation of the Ketogenic Diet (KD) and it will be started as soon as possible following surgery to achieve ketosis and reduction of blood sugar. Patients will receive standard chemoradiotherapy with fractionated external beam radiation (60Gy) and concurrent oral temozolomide chemotherapy followed by 12 adjuvant cycles of temozolomide chemotherapy on a standard dose schedule. Outcome measures of the study group will be compared to historic controls in the treatment arm from the European Organization for Research and Treatment of Cancer (EORTC) temozolomide study published by Roger Stupp et al, New England Journal of Medicine, March 10, 2005. Note: Gross Total Resection (GTR), Subtotal Resection (STR), temozolomide (Temodar), and radiation therapy are routine care for GBM and are not an investigational component of this study. Study end-points: Primary: Ketogenic diet (KD) tolerance and compliance in brain tumor patients. The diet will be considered tolerable if the patient chooses to remain compliant. Compliance is monitored by the dietician using self reporting of diet, blood glucose and blood ketone levels. Secondary: Overall survival, time to recurrence, health and therapy-related quality of life. Overall survival and progression free survival will be measured and compared to the historic controls who received chemoradiotherapy in standard dose scheduling. Laboratory correlate: Molecular/immunohistochemical analysis of tumors that do and do not respond to a KD.

Official Title
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Phase I/II Prospective Trial for Newly Diagnosed GBM, With Upfront Gross or Subtotal Resection, Followed by Ketogenic Diet With Radiotherapy and Concurrent Temodar(R) Chemotherapy Followed by Adjuvant Temodar(R) Chemotherapy.

Conditions
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Glioblastoma (GBM)

Intervention / Treatment
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* Dietary Supplement: Ketogenic Diet
* Radiation: Radiation therapy
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, 18 - 80 years of age, a single enhancing lesion of the brain with MRI appearance consistent with GBM Pathologic confirmation of GBM Zubrod Performance Scale (ZPS) < 2 Must be able to undergo MRI imaging with gadolinium Must have access to a computer and the internet (to use KetoCalculator© on-line Database) Exclusion Criteria: unable to undergo MRI with gadolinium genetic disorders of fat metabolism patients receiving sodium valproate (may cause false ketone reading in urine) diabetes enrolled in another treatment trial for GBM

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Ketogenic Diet<br>Subjects will adhere to a ketogenic diet prior to the start of and through radiation therapy course until the time of first scan after radiation ends. During radiation course, patients also take temozolomide daily. | Dietary Supplement: Ketogenic Diet<br>* Patients/families meet with the study dietician after surgery to discuss the ketogenic diet (KD), ask questions and plan clinic visits. Before radiation and chemotherapy begins, training takes place about the diet, meal planning and ketone/glucose monitoring. Ketosis will begin with the help of the dietitian one week before radiation begins. The patient will follow a classic 4/1 KD during chemo-radiation, followed by a modified Atkins diet during monthly chemotherapy. At the end of this period patients will follow a normal low carbohydrate diet similar to a Diabetic diet. The dietitian will follow the patient over the course of treatment. The patient will take and record ketone and glucose blood levels daily from start to end of treatment MRI scan, and meet with the dietitian weekly during radiation, at follow-up visits and on an as-needed basis.<br>Radiation: Radiation therapy<br>* Patients receive standard dose (60Gy/30 fractions) external beam radiation<br>Drug: Temozolomide<br>* patients receive standard dose (75 mg/kg/day) temozolomide by mouth daily with radiation for 6 weeks. patients will also have standard maintenance dose (150-200 mg/kg/day) for five days each month for 12 cycles following radiation course.<br>* Other names: chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | Number of participants with adverse events from initiation of ketogenic diet through end of radiation (while on ketogenic diet) | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | overall survival | 2 years | 
| time to progression | time to progression | 2 years | 
| quality of life | patient reported outcome of their quality of life using FACT-BR (version 4) survey | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketogenic Diet, Brain tumor, Glioma, Glioblastoma, Radiation, Chemotherapy, temozolomide