A Phase II Study of Everolimus (RAD001) for Children With Chemotherapy and/or Radiation-Refractory Progressive or Recurrent Low-Grade Gliomas

Inclusion Criteria:

- Patients must have histologic verification of one of the eligible diagnoses listed
here: Astrocytoma variants; fibrillary, protoplasmic, mixed: Pilocytic astrocytoma;
including pilomyxoid variants: Pleomorphic xanthoastrocytoma: infantile desmoplastic
astrocytoma: ganglioglioma: oligodendroglial tumors: mixed glioma.

- Patients must have received at least one cancer-directed therapy and patients with
allergies to carboplatin must have demonstrated progressive disease after cessation
of therapy.

- Must have at least one measurable site of disease that has not been previously
irradiated. If the patient has previous irradiation to the marker lesion(s), there
must be evidence of progression since radiation treatment.

- Patients must be between 3 years of age and 21 years of age

- Karnofsky Performance Status of 50% or greater for patients less than 10 years of age
or Lansky Score of 50% or greater for patients 10 and up.

- Participants must have recovered from the acute toxic effects of all prior
chemotherapy or radiotherapy prior to entering the study. Refer to protocol for
specific time restrictions with prior therapy completion.

- Adequate bone marrow function as defined in protocol

- Adequate renal function as defined in protocol

- Adequate liver function as defined in protocol

- Patients must have a fasting LDL cholesterol within the normal range per
institutional guidelines

- Patients taking cholesterol lowering agent must be on a single medication and on a
stable dose for at least 4 weeks

- Fasting serum cholesterol as outlined in protocol

- Patients must not be taking enzyme-inducing anticonvulsants

- Patients may not be currently receiving strong inhibitors of CYP3A4

Exclusion Criteria:

- Presence of NF1 by clinical examination or by genetic testing

- Patients who have had a major surgery or significant traumatic injury within 2 weeks
of start of study drug, patients who have not recovered from teh side effects of any
major surgery, or patients that may require major surgery during the course of the
study

- Patients receiving chronic, systemic treatment with corticosteroids or another
immunosuppressive agent. Topical or inhaled are allowed

- Evidence of plexiform neurofibroma, malignant peripheral nerve sheath tumor, or other
cancer requiring treatment with chemotherapy or radiation therapy

- Uncontrolled brain or leptomeningeal metastases from plexiform neurofibromas,
malignant peripheral nerve sheath tumors, or other cancers (other than astrocytoma
variants; fibrillary, protoplasmic, mixed: Pilocytic astrocytoma; including
pilomyxoid variants: Pleomorphic xanthoastrocytoma: infantile desmoplastic
astrocytoma: ganglioglioma: oligodendroglial tumors: mixed glioma), including
patients who continue to require glucocorticoids for control of symptoms related to
brain or leptomeningeal metastases.

- Other malignancies within the past three years except for adequately treated
carcinoma of the cervix or basal or squamous cell carcinomas of the skin

- Patients who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation in the study (see protocol for
examples)

- Known history of HIV seropositivity

- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of RAD001

- Active, bleeding diathesis or oral anti-vitamin K medication (except low dose
coumarin)

- Female patients who are pregnant or breast feeding

- Prior treatment with an mTOR inhibitor

- Known hypersensitivity to RAD001 or other rapamycins or to is excipients

- Dental braces or prosthesis that interferes with tumor imaging

- Patients with a positive history of Hepatitis B or Hepatitis C

- Patients should not receive immunization with attenuated live vaccines within one
week of study entry or during study period.