Everolimus in Treating Younger Patients with Recurrent or Progressive Low-Grade Gliomas

Inclusion Criteria

• Patients must have progressive or recurrent confirmed low-grade glioma (World Health Organization [WHO] grade I or II) that was confirmed histologically
• Tissue from the initial diagnosis or recurrence must be made available for correlative testing
• Depending on the stage of the protocol, pathway activation based on p-S6 will need to be done in real time to assess if patient is eligible; as of April 2017, pathway activation does not need to be performed in real time to access eligibility
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions on magnetic resonance imaging (MRI)
• Patients may have had treatment (chemotherapy and/or radiotherapy) or no treatment 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
• Patient must have a Karnofsky (if >= 16 years of age) or Lansky performance score (if =< 15 years of age) of >= 50 by the time of registration; 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
• Absolute neutrophil count (ANC) >= 1,000/mm^3 before starting therapy
• Platelet count of >= 100,000/mm^3 before starting therapy
• Hemoglobin >= 9 gm/dL before starting therapy; eligibility level for hemoglobin may be reached by transfusion
• Serum glutamate pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) =< 2.5 times upper limit or normal (ULN) before starting therapy
• Bilirubin =< 1.5 times ULN before starting therapy
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows: * Age: Maximum serum creatinine (mg/dL) * 3 to < 6 years: 0.8 (male and female) * 6 to < 10 years: 1 (male and female) * 10 to < 13 years: 1.2 (male and female) * 13 to < 16 years: 1.5 (male) 1.4 (female) * >= 16 years: 1.7 (male) 1.4 (female)
• 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 < 350 mg/dL and triglycerides < 400 mg/dl before start of therapy
• Patients must have normal pulmonary function testing for age based on pulse oximetry
• Female patients 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 female patient 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, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines
• Hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb) blood test must be done at screening for all patients; patients who test positive for hepatitis C antibodies or the hepatitis B antigen are ineligible
• A known history of human immunodeficiency virus (HIV) seropositivity; HIV-positive patients on combination antiretroviral therapy are ineligible
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent; Note: Patients who are currently using inhaled, intranasal, ocular, topical or other non-oral or non-IV steroids are not necessarily excluded from the study but need to be discussed with the study chair
• 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