Inclusion Criteria

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:

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