Everolimus for Children With NF1 Chemotherapy-Refractory Radiographic Progressive Low Grade Gliomas

Inclusion Criteria: * Diagnosis: All patients must have a radiographically progressive low-grade glioma and at least two of the following diagnostic criteria for NF1, and/or a pathogenic NF1 gene mutation demonstrated in peripheral blood-derived DNA: * Six or more café-au-lait spots (greater than or equal to 0.5 cm in prepubertal subjects or greater than or equal to 1.5 cm in postpubertal subjects) * Freckling in the axilla and/or inguinal region * Plexiform neurofibroma * Two or more Lisch nodules * A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex) * A first-degree relative with NF1 * An optic pathway glioma * Disease Status: All patients must have radiographically progressive low-grade glioma (including NF1 related visual pathway gliomas) after failure of a carboplatin-containing regimen. Patients with recurrent/progressive disease do not require a biopsy to confirm the diagnosis. * Evaluable or Measurable Disease: Patients must have at least one evaluable or measurable site of disease according to criteria described in Section 9. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation. * Age: Patients must be greater than 1 years and less than or equal to 21 years of age at the time of study entry. * Performance Level: Karnofsky 50% for patients greater than 10 years of age and Lansky 50% for patients 10 years of age (Appendix I). Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * Prior Therapy * Patients must have failed or not been able to tolerate a carboplatin-based regimen. * Patients must have fully recovered from the acute toxic effects of all prior chemotherapy or radiotherapy prior to entering this study. * Myelosuppressive chemotherapy: Must not have received within 4 weeks of entry onto this study (6 weeks if prior nitrosourea). * Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor. * Biologic (anti-neoplastic agent): At least 14 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 14 days after administration, this period must be extended beyond the time during which adverse events are known to occur. These patients must be discussed with the Study Chair on a case-by-case basis. * Investigational Drugs: Patients must not have received an investigational drug within 14 days. * Steroids: Patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary. * Cytochrome P450 3A4 (CYP3A4) inhibitors: Patients may not be currently receiving strong inhibitors of CYP3A4, and may not have received these medications within 1 week prior to study entry. These include: * Antibiotics: clarithromycin, erythromycin, troleandomycin Anti-HIV agents: delavirdine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir * Antifungals: itraconazole, ketoconazole, fluconazole (doses greater than 200 mg/day), voriconazole * Antidepressants: nefazodone, fluvoxamine Calcium channel blockers: verapamil, diltiazem * Miscellaneous: amiodarone, * In addition, grapefruit juice should be avoided, as it inhibits CYP3A4. * CYP3A4 inducers: Patients must also avoid St. John's Wort, an inducer of CYP3A4 * Enzyme inducing anticonvulsants: Patients may not be taking enzyme-inducing anticonvulsants, and may not have received these medications within 1 week prior to study entry, as these patients may experience different drug disposition. These medications include: * Carbamazepine (Tegretol) * Felbamate (Felbatol) * Phenobarbitol * Phenytoin (Dilantin) * Primidone (Mysoline) * Oxcarbazepine (Trileptal) * Radiation therapy (XRT): * 6 months must have elapsed if the patient has received involved field XRT or gamma knife that includes all target lesions (i.e., there is no restriction if a new lesion arises outside the radiation field or a non-irradiated lesion progresses); * 6 months must have elapsed if the patient has received craniospinal XRT. * 6 weeks must have elapsed if patient has received radiation to areas outside optic glioma. * Surgery: At least 2 weeks must have elapsed since undergoing major surgery. * Organ Function Requirements: * Adequate Bone Marrow Function Defined as: * Peripheral absolute neutrophil count (ANC) \_\_1000/\_\_L * Platelet count \_\_ 100,000/\_\_ L (transfusion independent) * Hemoglobin \_\_ 9.0 gm/dL (may receive red blood cell (RBC) transfusions) * Adequate Renal Function Defined As: \- A serum creatinine based on age as follows: Age (Years) Maximum Serum Creatinine (mg/dL) \_\_5 / 5 less than age \_\_ 10 / 10 less than age \_\_ 15/ greater than 15 0.8 1.0 1.2 1.5 OR a creatinine clearance or radioisotope glomerular filtration rate (GFR) \_\_ 70ml/min/1.73 m2 * Adequate Liver Function Defined As: * Bilirubin (sum of conjugated + unconjugated) \_\_ 1.5 x upper limit of normal (ULN) for age, and * Serum glutamic pyruvic transaminase (SGPT) (alanine transaminase (ALT)) \_\_ 5 x upper limit of normal (ULN) for age, and * Serum albumin \_\_ 2 g/dL * International normalised ratio (INR) less than 1.3 (or less than 3 on anticoagulants) * Serum creatinine less than or equal to 1.5x ULN * Fasting Low-density lipoprotein cholesterol (LDL) Cholesterol: * Patients must have a fasting LDL cholesterol within the normal range per institutional guidelines * Patients taking a cholesterol lowering agent must be on a single medication and on a stable dose for at least 4 weeks * Fasting Serum Cholesterol: \- less than or equal to 300 mg/dL OR less than or equal to 7.75 mmol/L AND fasting triglycerides less than or equal to 2.5x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication. * Signed informed consent/assent Exclusion Criteria: * Chronic treatment with systemic steroids or another immunosuppressive agent. Patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary. * Evidence of an active lesion including: plexiform neurofibroma, malignant peripheral nerve sheath tumor, or other cancer requiring concurrent treatment with chemotherapy or radiation therapy. Patients not requiring treatment for these lesions are eligible for this protocol. * Patients who: * have had a major surgery or significant traumatic injury within 2 weeks of start of study drug; * have not recovered from the side effects of any major surgery (defined as requiring general anesthesia but excluding a procedure for insertion of central venous access), or * may require major surgery during the course of the study. * Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin. * Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases. * Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin). * Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: * symptomatic congestive heart failure of New York heart Association Class III or IV. * unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease. * severely impaired lung function. * uncontrolled diabetes as defined by fasting serum glucose greater than 1.5x ULN. * active (acute or chronic) or uncontrolled severe infections. * liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis. * Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal (GI) tract ulceration). * A known history of HIV seropositivity or known immunodeficiency. * Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection). A nasogastric tube (NG tube) is allowed. * Women who are pregnant or breast feeding. * Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during the time they are receiving the study drug and for 3 months thereafter. Abstinence is an acceptable method of birth control. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Women of childbearing potential will be given a pregnancy test within 7 days prior to administration of RAD001 and must have a negative urine or serum pregnancy test. * Patients who have received prior treatment with a mammalian target of rapamycin (mTOR) inhibitor. * Dental braces or prosthesis that interferes with tumor imaging. * History of noncompliance to medical regimens. * Patients unwilling to or unable to comply with the protocol or who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.