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

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