AEE788 and Everolimus in Treating Patients With Recurrent or Relapsed Glioblastoma Multiforme

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