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

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).

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.