Everolimus With and Without Temozolomide in Adult Low Grade Glioma

Inclusion Criteria:

* Age \>= 18 years
* Karnofsky performance scale score (KPS) \>= 60
* Adequate bone marrow function as shown by: Absolute Neutrophil Count (ANC) \>= 1.5 x 10\^9/L, Platelets \>= 100 x 10\^9/L, hemoglobin \>= 9.0 g/dL;
* Adequate liver function as shown by: Total serum bilirubin ≤ 2.0 mg/dL, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<=2.5x upper limit of normal (ULN), International Normalized Ratio (INR) \<= 2;
* Adequate renal function: serum creatinine \<=1.5 x ULN;
* Fasting serum cholesterol \<= 300 mg/dL OR \<= 7.75 mmol/L AND fasting triglycerides \<= 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 with confirmed reduction of lab values to within eligibility parameters;
* Signed informed consent prior to any screening procedures
* Histologically proven supratentorial low-grade glioma at initial diagnosis; pathology must have been reviewed by University of California, San Francisco (UCSF) neuropathology. Eligible low-grade gliomas include: astrocytoma, oligodendroglioma and mixed oligoastrocytoma. Pilocytic astrocytomas are excluded.
* Patient's tumor must have documentation of the presence of an Isocitrate dehydrogenase 1 (IDH1) and/or Isocitrate dehydrogenase 2 (IDH2) mutation of any type.
* Results of 1p/19q chromosomal status and p-PRAS40 testing must be available to permit treatment selection.
* Evaluable disease
* Must begin treatment within 120 days of surgical procedure

Exclusion Criteria:

* No prior tumor treatment except for surgery at diagnosis, and must have adequately recovered from surgery
* Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus) or to temozolomide
* Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus or temozolomide
* Uncontrolled diabetes mellitus as defined by HbA1c \> 8.0% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary;
* Any severe and/or uncontrolled medical conditions such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease; symptomatic congestive heart failure of New York heart Association Class III or IV; active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus(HBV-DNA and/or positive Hepatitis B Surface Antigen (HbsAg), quantifiable hepatitis C virus (HCV-RNA); known severely impaired lung function (spirometry and Diffusing capacity of the lungs for carbon monoxide (DLCO) 50% or less of normal and O2 saturation 88% or less at rest on room air); active, bleeding diathesis;
* Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled corticosteroids are allowed, and treatment with low dose Decadron (\<= 3mg daily) is allowed;
* Known history of HIV seropositivity;
* Positive serological test results for hepatitis B
* Positive serological test result for hepatitis C
* Recipients of live attenuated vaccines within 1 week of start of treatment and during the study. Avoid close contact with others who have received live attenuated vaccines. Examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines;
* History of another primary malignancy, with the exceptions of: non-melanoma skin cancer, and carcinoma in situ of the cervix, uterus, or breast, unless the patient has been disease free for \>= 3 years;
* History of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study;
* Currently part of or have participated in any clinical investigation with an investigational therapeutic drug within 1 month prior to dosing;
* Pregnant or nursing (lactating) women;
* Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, who are not willing to use adequate methods of contraception during the study and for 8 weeks after the end of treatment.
* Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential.
* Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment