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

Inclusion Criteria:

- Patients must have a Karnofsky performance status of > 60

- Patients must have a life expectancy > 8 weeks

- Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x
109/L, Hb >9 g/dL

- Adequate liver function as shown by:

- serum bilirubin ≤ 1.5 x ULN

- INR < 1.3 (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of
warfarin or on a stable dose of LMW heparin for > 2 weeks at the time of
registration)

- ALT and AST ≤ 2.5x ULN

- Adequate renal function: serum creatinine ≤ 1.5 x ULN

- Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5
x 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.

- Patients must have histologically proven intracranial low-grade glioma at initial
diagnosis.

- Patients must have unequivocal evidence for tumor recurrence or progression by
histology as determined by review of pathology by an attending neuro-pathologist at
UCSF

- If most recent histology shows progression to high grade glioma, patients must have
had prior radiotherapy in order to be eligible

- Paraffin-embedded sections of tissue acquired from surgery at the time of suspected
recurrence must be available for analysis

- Patients must have evidence for tumor recurrence or progression by MRI as determined
by radiographic review of images by an attending neuro-oncologist or
neuro-radiologist at UCSF

- An MRI must be used throughout the period of protocol treatment for tumor measurement

- Patients may have had treatment (including radiotherapy) for any number of relapses
prior to this recurrence

- Patients must be at least 4 weeks from the completion of any radiation therapy

- Patients must be less than 4 months from the surgical procedure for this recurrence

- Patients must have recovered from the toxic effects of prior therapy:

- 4 weeks from any investigational agent.

- 4 weeks from prior cytotoxic therapy (except 6 weeks from nitrosoureas, 3 weeks
from procarbazine, 3 weeks from vincristine)

- 3 weeks for non-cytotoxic or biologic agents e.g., interferon, tamoxifen,
thalidomide, cis-retinoic acid, etc

Exclusion Criteria:

- Patients, who have not recovered from the side effects of a major surgery or
significant traumatic injury or patients that may require major surgery during the
course of the study

- Patients receiving chronic, systemic treatment with corticosteroids or another
immunosuppressive agent. Topical or inhaled corticosteroids, and treatment with low
dose Decadron (£ 6mg daily) are allowed.

- Other malignancies within the past 3 years except for adequately treated carcinoma of
the cervix or basal or squamous cell carcinomas of the skin.

- Other than surgery, patients may not have therapy for this recurrence (including
radiation). Supportive care such as steroids or anti-epileptics does not constitute
treatment of recurrence

- Patients must not be on an enzyme inducing antiepileptic agent within 5 days of
starting protocol therapy

- Patients must not have any significant medical illnesses that in the investigator's
opinion cannot be adequately controlled with appropriate therapy or would compromise
the patient's ability to tolerate this therapy.

- 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 are ineligible.

- Patients should not receive immunization with attenuated live vaccines within one
week of study entry or during study period

- Uncontrolled brain or all leptomeningeal metastases, including patients who continue
to require glucocorticoids for brain or leptomeningeal metastases

- 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

- Impaired lung function: Oxygen saturation 88% or less at rest on room air by Pulse
Oximetry. If O2 saturation is ≤ 88% at rest, further pulmonary function tests (PFTs)
should be ordered to confirm normal pulmonary function and eligibility.

- uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN

- active (acute or chronic) or uncontrolled severe infections

- liver disease such as cirrhosis, chronic active hepatitis or chronic persistent
hepatitis

- A known history of HIV seropositivity

- 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)

- Patients with an active, bleeding diathesis

- Female patients who are pregnant or breast feeding, or adults of reproductive
potential who are not using effective birth control methods.

- Patients who have received prior treatment with an mTOR inhibitor (sirolimus,
temsirolimus, everolimus).

- Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins
(sirolimus, temsirolimus) or to its excipients