Ketogenic Diet in Children With Malignant or Recurrent/Refractory Brain Tumor

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the effect of the ketogenic diet on tumor size and quality of life in pediatric patients with malignant or recurrent/refractory brain tumors.

Detailed Description
-----------------
Brain tumors account for nearly 20% of all childhood malignancies. Of these, gliomas represent 50% of all brain tumors in children and young adults. Gliomas are classically divided into two subtypes - low-grade and high-grade. Low-grade gliomas (LGG) include pilocytic astrocytomas and diffuse astrocytomas, and high-grade gliomas (HGG) include anaplastic astrocytoma and glioblastoma multiforme. Although patients with grade I and II tumors have a good prognosis with 5-year overall survival rates of 80-90%, those cases that are recurrent, refractory, and/or unresectable remain a challenge. The prognosis of children and young adults with recurrent or refractory malignant brain tumors remains poor despite dramatic improvements in treatment over the past few decades, with only a minority achieving long-term survival if recurrence occurs following initial surgical resection and adjuvant chemotherapy. For patients with HGG prognosis remains dismal despite aggressive treatment. In this subset of patients, the 5-year overall survival for anaplastic astrocytoma ranges from 20-40% and for glioblastoma 15-20%. Diffuse intrinsic brain stem gliomas (DIPG) have the worst overall prognosis with a nine-month mean overall survival and with most patients dying from the disease within 2 years. Thus, the development of new treatment protocols for children and young adults with both high grade gliomas and with recurrent or refractory low grade gliomas is crucial to improving the survival rates of these patients. The Ketogenic Diet (KD) has been in clinical use for nearly a century, initially designed to mimic the effects of starvation. Over the last two decades metabolic studies have been gaining momentum as increasingly promising in disease modification of central nervous system disorders and tumors. Tests in animals and studies in adult patients with brain tumors have shown that there are advantages to using the ketogenic diet. These include: improved response of the tumor to standard treatment (chemotherapy/radiation) and improvement in quality of life measures (alertness).

Official Title
-----------------
A Phase II Study of the Ketogenic Diet in Children With Malignant or Recurrent/Refractory Brain Tumor

Conditions
-----------------
Brain Tumors

Intervention / Treatment
-----------------
* Other: Ketogenic Diet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis Medulloblastoma, high-grade glioma, low-grade glioma, and ependymoma are eligible. Other central nervous system tumors may be considered for treatment at discretion of investigator. Pathology is required unless diffuse intrinsic pontine glioma or optic pathway tumor. The patient should have failed first line therapy and be considered refractory, relapsed, or recurrent. Exceptions are Grade III and Grade IV gliomas including brain stem gliomas who can be enrolled at initial diagnosis. Prior Therapy Patients should have already had first line standard of care therapy, unless their initial diagnosis is high grade glioma or DIPG in which case they are eligible. Patients with high grade glioma can be enrolled after the completion of initial radiation. Investigator discretion may also be used. Organ Function Requirements A. Functioning gastrointestinal system, i.e. ability to chew and swallow or alternative means of nutrition therapy such as a gastrostomy or jejunostomy tube B. SGPT (ALT) < 3 x upper normal limit; Total Bilirubin ≤ 2 x upper normal limit C. No active pancreatitis D. No arrhythmia or prolonged QT. Exclusion Criteria: History of cardiac arrhythmia Patient unable to chew/swallow and who do not consent to alternative methods of nutrition support, e.g. nasogastric or nasoduodenal tube, or gastrostomy or jejunostomy tube placement.

Ages Eligible for Study
-----------------
Minimum Age: 12 Months
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Interventional Model Description: Ketogenic Diet will be initiated as inpatient, once all necessary studies are obtained and reviewed. The classic ketogenic diet will be initiated, and once ketosis is reached and patient demonstrates tolerance to diet he/she will be discharged home. Follow-up visits will be necessary up to 1 year.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Ketogenic Diet<br>Participants will be provided a consultation with a ketogenic dietitian, and test the tolerance to the diet in an inpatient mode | Other: Ketogenic Diet<br>* Once tolerance to the diet has been assessed, participants will be placed in the ketogenic diet, followed-up every three months until the one year completion.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | To evaluate the overall response rate of subjects with malignant or refractory brain tumors receiving dietary therapy with the ketogenic diet | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life Measures | To evaluate the changes of quality of life of subjects with relapsed or refractory brain tumors receiving dietary therapy with the ketogenic diet using age-appropriate quality of life modules (Peds QL). | one year | 
| Ketosis Levels | To compare the betahydroxybutyrate level to decrease tumor size using MRI. | one year | 
| Blood Glucose Levels | To compare average blood glucose during ketogenic diet initiation compared to decrease in tumor size at time of first follow-up MRI. | one year | 
| Correlation of ketosis levels and ketogenic diet | To evaluate correlation between degree of ketosis (betahydroxybutyrate level) and ketogenic diet ratio. | one year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ketogenic Diet, brain tumors