Everolimus in Treating Patients With Recurrent or Progressive Low-Grade Glioma

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