PNOC 001: Phase II Study of Everolimus for Recurrent or Progressive Low-grade Gliomas in Children

Inclusion Criteria: --Patients must have radiographic progressive or recurrent confirmed world health organization (WHO) grade I or II astrocytomas, that was confirmed histologically. Progressive or recurrent disease should be based on MRI according to the definition below. Eligible histologies: * Pilocytic Astrocytoma - 90600112 * Astrocytoma, Low Grade (Fibrillary astrocytoma, WHO Grade 2) - 10065886 * Astrocytoma, Low Grade (Low-grade Astrocytoma, not otherwise specified (NOS), WHO Grade 2) - 10003571 * Tissue from the initial diagnosis or recurrence must be made available for correlative testing. * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions on MRI. * Patients may have had treatment (chemotherapy and/or radiotherapy) for any number of relapses prior to this recurrence. * Patients must have received their last dose of myelosuppressive anticancer chemotherapy at least three (3) weeks prior to study registration or at least six (6)weeks of nitrosourea. * Patients must have received their last dose of other investigational or biological agent \> 7 days prior to study entry. For agents that have known adverse events occurring beyond 7 days after administration, this period should be extended beyond the time during which adverse events are known to occur. This should be discussed with the study chair. * If patients received prior monoclonal antibody treatment, at least three half-lives must be elapsed by the time of treatment initiation. These patients should also be discussed with the study chair. * Patients must have received their last fraction of craniospinal or focal radiation to primary tumor or other sites \>12 weeks (3 months) prior to registration. --Age ≥3 and ≤21 years. * Because no dosing or adverse event data are currently available on the use of everolimus in patients \<3 years of age, these young children are excluded from this study. * Life expectancy of greater than 8 weeks. * Patients must be able to swallow pills. * Patient must have a Karnofsky (if ≥ 16 years of age) or Lansky Performance score (if ≤ 16 years of age) of ≥50 by the time of registration. * Patients must have adequate bone marrow function (ANC ≥ 1,000/mm3, platelet count of ≥ 100,000/mm3, and hemoglobin ≥ 9 gm/dL) before starting therapy. Eligibility level for hemoglobin may be reached by transfusion. * International Normalized Ratio (INR) ≤1.5. (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of low molecular weight (LMW) heparin for \>2 weeks at time of randomization). * Patients must have adequate liver function (SGPT/alanine aminotransferase (ALT) ≤ 2.5 times ULN and bilirubin ≤ 1.5 times ULN) before starting therapy. * Patients must have adequate renal function (serum creatinine ≤ 1.5 times institutional ULN for age or Glomerular filtration rate (GFR) ≥ 70 ml/min/1.73 m2) before starting therapy. * Patients must have cholesterol level \<350 mg/dL and triglycerides \< 400 mg/dL before starting therapy. In case one or both of these are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication and documentation of cholesterol \< 350mg/dL and triglycerides \< 400mg/dl before start of therapy. * Patients must have normal pulmonary function testing for age based on pulse oximetry. * The effects of everolimus on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because everolimus are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Female patients of child bearing potential must not be breastfeeding or pregnant as evidenced by a negative pregnancy test. Exclusion Criteria: * Patients with primary spinal cord tumors * Patients receiving concomitant medication that may interfere with study outcome. For example, patients cannot be on enzyme inducing anticonvulsants like phenytoin. * Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, bacille Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines * Hepatitis B/C blood test must be done at screening for all patients. Patients who test positive for Hepatitis C antibodies and the Hepatitis B antigen are ineligible. * A known history of HIV seropositivity. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with everolimus. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. * Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed. * Patients may not have therapy for this recurrence (including radiation). * Patients who do not have measurable disease on MRI. * Patients who have been previously treated with an mTOR inhibitor. * Patients with a known hypersensitivity to everolimus or other rapamycins (e.g. sirolimus, temsirolimus). * Patients receiving any other concurrent anticancer or investigational therapy. * Patients with any clinically significant unrelated systemic illness that would compromise the patient's ability to tolerate protocol therapy. * Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection. * Patients with inability to return for follow-up visits to assess toxicity to therapy. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years. Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. Hepatitis B Virus (HBV) DNA and Hepatitis C Virus (HCV) RNA Polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.