DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme, meeting 1 of the following criteria:

  • Phase I

    • In first or second recurrence or relapse
    • At least 1 measurable or evaluable enhancing lesion by gadolinium MRI (Gd-MRI) of the brain within the past 3 weeks

  • Phase II, group 1

    • In first or second recurrence or relapse by Gd-MRI of the brain within the past 3 weeks
    • Requires tumor biopsy OR surgical resection for tumor debulking or for confirmation of recurrence

  • Phase II, group 2

    • In first recurrence or relapse
    • At least 1 bidimensionally measurable enhancing lesion (≥ 1.5 cm^2 using product of the largest perpendicular diameters) by Gd-MRI of the brain within the past 3 weeks
• Multifocal disease allowed

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Hemoglobin ≥ 9 g/dL
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• No acute or chronic liver disease

Renal

• Total calcium (corrected) normal*
• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 50 mL/min
• No proteinuria by dipstick OR
• Total urinary protein ≤ 500 mg AND creatinine clearance ≥ 50 mL/min by 24-hour urine collection
• No acute or chronic renal disease NOTE: *Supplements allowed

Cardiovascular

• LVEF ≥ 45% by MUGA or echocardiogram
• No complete left bundle branch block
• No requirement for a cardiac pacemaker
• No congenital long QT syndrome
• No ventricular or atrial tachyarrhythmias
• No clinically significant resting bradycardia, defined as < 50 beats per minute
• QTc ≤ 480 msec by ECG
• No right bundle branch block and left anterior hemiblock (bifascicular block)
• No uncontrolled hypertension OR history of labile hypertension
• No unstable angina pectoris OR angina pectoris occurrence within the past 3 months
• No congestive heart failure
• No acute myocardial infarction within the past 3 months
• No history of poor compliance with an antihypertensive regimen
• No other impaired cardiac function or clinically significant cardiac disease

Gastrointestinal

• No unresolved diarrhea ≥ grade 2

• No impairment of gastrointestinal (GI) function or GI disease that would significantly alter absorption of study drugs, including any of the following:

  • Ulcerative disease
  • Uncontrolled nausea
  • Vomiting
  • Malabsorption syndrome

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• Potassium normal*
• Magnesium normal*
• Phosphorus normal*
• Cholesterol ≤ 300 mg/dL (treatment allowed)
• Triglycerides ≤ 2.5 times ULN (treatment allowed)
• No known HIV positivity
• No peripheral neuropathy ≥ grade 2
• No uncontrolled diabetes
• No active or uncontrolled infection
• No other severe and/or uncontrolled medical condition that would preclude study participation or compliance

• No contraindication to MRI, including any of the following:

  • Cardiac pacemaker
  • Ferromagnetic metal implants other than those approved as safe for use with magnetic resonance scanners (e.g., some types of aneurysm clips or shrapnel)
  • Claustrophobia
  • Obesity exceeding magnetic resonance equipment limits
• No other clinically significant primary malignancy requiring active intervention NOTE: *Supplements allowed

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 2 weeks since prior hematopoietic colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) except epoetin alfa
• More than 2 weeks since prior immunotherapy and recovered
• No concurrent biologic therapy
• No concurrent prophylactic hematopoietic growth factors (e.g., G-CSF or GM-CSF) unless approved by the study sponsor

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• Prior polifeprosan 20 with carmustine implant (Gliadel® wafer) allowed
• No other concurrent chemotherapy

Endocrine therapy

• Must be on stable or deceasing doses of steroids for at least 7 days before baseline Gd-MRI of the brain and before starting study drug
• No concurrent tamoxifen

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery

• More than 1 week since prior tumor biopsy
• More than 2 weeks since prior surgical resection
• More than 2 weeks since prior major non-CNS surgery and recovered
• No prior small bowel resection

Other

• At least 2 weeks since prior and no concurrent enzyme-inducing anticonvulsant drugs
• More than 4 weeks since prior investigational drugs and recovered
• No prior epidermal growth factor receptor- or ErbB-2-directed therapy (phase II only)
• No prior vascular endothelial growth factor (VEGF) or VEGF receptor-directed therapy (phase II only)
• No prior mTOR-directed therapy (phase II only)
• No concurrent therapeutic warfarin

• No concurrent treatment with any medication that may prolong QT interval, including any of the following:

  • Quinidine
  • Procainamide
  • Disopyramide
  • Amiodarone
  • Sotalol
  • Bretylium
  • Ibutilide
  • Thioridazine
  • Mesoridazine
  • Chlorpromazine
  • Amitriptyline
  • Imipramine
  • Desipramine
  • Doxepin
  • Erythromycin
  • Clarithromycin
  • Ketoconazole
  • Halofantrine
  • Quinine
  • Chloroquine
  • Mefloquine
  • Moxifloxacin
  • Gatifloxacin
  • Pimozide
  • Risperidone
  • Ziprasidone
  • Venlafaxine
  • Maprotiline
  • Lithium
  • Pentamidine
  • Droperidol
  • Dolasetron
• No concurrent digoxin or verapamil
• No concurrent tacrolimus
• No other concurrent investigational agents