Phase II Trial of RAD001 in Patients With Recurrent Low Grade Glioma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed intracranial low-grade glioma* at initial diagnosis,
including any of the following histological subtypes:

- Astrocytoma

- No pilocytic astrocytomas

- Oligodendroglioma

- Mixed oligoastrocytoma NOTE: *Histologically confirmed progression to high-grade
gliomas are allowed provided patient has undergone prior radiotherapy

- Evaluable disease

- Unequivocal evidence of tumor recurrence or progression by histology and MRI, as
determined by the following:

- Histological review of pathology by an attending neuro-pathologist at the
University of California San Francisco (UCSF)

- Radiographic review of MRI* (performed within the past 14 days) by an attending
neuro-oncologist or neuro-radiologist at UCSF NOTE: *MRI must be performed after
≥ 5 days on a stable dose of steroids or a new baseline MRI is required

- Paraffin-embedded tissue samples acquired from surgery at time of recurrence must be
available

- No leptomeningeal or uncontrolled brain metastases, including those who require
glucocorticoids for their metastases

- Must be registered in University of California San Francisco Neuro-Oncology database

PATIENT CHARACTERISTICS:

- Karnofsky performance status 60-100%

- Life expectancy > 8 weeks

- ANC ≥ 1.5 x 10^9/L

- Platelet count ≥ 100 x 10^9/L

- Hemoglobin > 9 g/dL

- Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)

- INR < 1.3 (or < 3 on anticoagulants)

- ALT and AST ≤ 2.5 times ULN

- Serum creatinine ≤ 1.5 times ULN

- Fasting serum cholesterol* ≤ 300 mg/dL OR ≤ 7.75 mmol/L

- Fasting triglycerides* ≤ 2.5 times ULN NOTE: *If one or both of these thresholds is
exceeded, the patient can only be included after initiation of appropriate lipid
lowering medication

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No significant medical illnesses that, in the opinion of the investigator, cannot be
adequately controlled with appropriate therapy, or would compromise the patient's
ability to tolerate study therapy

- No other cancer except nonmelanoma skin cancer or carcinoma in-situ of the cervix,
unless in complete remission and off all therapy for that disease within the past 3
years

- No active, bleeding diathesis

- No severe and/or uncontrolled medical conditions or other conditions that would
preclude participation in the study, including any of the following:

- NYHA class III-IV symptomatic congestive heart failure

- Unstable angina pectoris

- Myocardial infarction within the past 6 months

- Serious uncontrolled cardiac arrhythmia

- Other clinically significant cardiac disease

- Severely impaired lung function (i.e., oxygen [O_2] saturation 88% or less at
rest on room air by pulse oximetry must undergo further pulmonary function tests
to confirm normal pulmonary function and eligibility)

- Uncontrolled diabetes, defined by fasting serum glucose > 1.5 times ULN

- Active (acute or chronic) or uncontrolled severe infections

- Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent
hepatitis)

- No impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of everolimus, including any of the following:

- Ulcerative disease

- Uncontrolled nausea

- Vomiting

- Diarrhea

- Malabsorption syndrome

- Small bowel resection

- No known HIV positivity

- No known hypersensitivity to everolimus or other rapamycins (i.e., sirolimus,
temsirolimus) or to its excipients

- No history of noncompliance to medical regimens

- Must be willing and able to comply with the protocol

PRIOR CONCURRENT THERAPY:

- Recovered from all prior therapy

- Treatment for relapses prior to this recurrence allowed

- No prior therapy for this recurrence (e.g., radiotherapy)

- Supportive care (e.g., steroids or antiepileptics) does not constitute treatment
of recurrence)

- No prior mTOR inhibitor (i.e., sirolimus, temsirolimus, or everolimus)

- More than 5 days since prior enzyme-inducing antiepileptic agent

- More than 1 week since prior and no concurrent immunization with attenuated live
vaccines

- Less than 4 months since prior surgical procedure for this recurrence

- At least 2 weeks since prior non-cytotoxic or biologic agents (e.g., interferon,
tamoxifen, thalidomide, or cis-retinoic acid)

- At least 4 weeks since prior radiotherapy

- At least 4 weeks since prior cytotoxic therapy (≥ 6 weeks since nitrosourea, 3 weeks
since procarbazine, and 2 weeks since vincristine)

- At least 4 weeks since prior and no concurrent investigational agent

- No other concurrent anticancer agents

- Concurrent enzyme-inducing antiepileptic agents allowed provided treatment is limited
to no more than 10 days during study