Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically proven high-grade glioma (glioblastoma, anaplastic astrocytoma,
anaplastic oligodendroglioma, mixed anaplastic oligoastrocytoma, anaplastic
ependymoma) that is progressive or recurrent following standard upfront radiation
therapy + temozolomide

- Measurable contrast-enhancing progressive or recurrent high-grade glioma (single or
multiple lesions) by MRI imaging within 30 days of starting treatment

- Must have a plan for retreatment with temozolomide at 150-200 mg/m² for 5 days per
cycle; each cycle = 28 days

- Must have previously tolerated at least one cycle of adjuvant temozolomide
therapy in the prior treatment of the glioma

PATIENT CHARACTERISTICS:

- Karnofsky performance status ≥ 60%

- Hemoglobin ≥ 9 g/dL

- Absolute neutrophil count ≥ 1,500/µL

- Platelets ≥ 100,000/µL

- Total bilirubin < or equal to 3 times institutional upper limit of normal (ULN)

- AST(SGOT)/ALT(SGPT) < or equal to 3 times ULN

- Creatinine normal OR creatinine clearance ≥ 50 mL/min

- Serum potassium, magnesium, and calcium levels normal (may be corrected to those
levels by supplementation during screening period)

- Not pregnant or nursing

- Negative pregnancy test

- Women of childbearing potential and men must agree to use adequate contraception

- Able to tolerate MRIs

- CT scans cannot be substituted for MRIs in this study

- No concurrent malignancy except curatively treated basal or squamous cell carcinoma
of the skin or carcinoma in situ of the cervix, breast, or bladder

- Subjects with prior malignancies must be disease-free for ≥ five years

- Mini-Mental State Exam score of ≥ 15

- Patients must identify a caregiver/support person who will agree to assist with the
remote cardiac monitor and taking/recording blood pressure at home

- No serious concurrent infection or medical illness, which would jeopardize the
ability of the subject to receive the treatment outlined in this protocol with
reasonable safety

- No uncontrolled intercurrent illness including, but not limited to, hypertension,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements

- No history of known, active hepatitis

- No screening QTc interval ≥ 450 mSec for males or 470 mSec for females

- No PR interval > 250 mSec

- No systolic blood pressure < or equal 100 mm Hg at baseline

- No history (within six months) of myocardial infarction, unstable angina,
uncontrolled hypertension, or congestive heart failure

- No high-grade (second degree or above) AV block or persistent sinus bradycardia of
less than 50 BPM

- No known HIV-positivity

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered to CTCAE grade < or equal 2 from toxicities related to prior therapy

- An interval of at least 3 months must have elapsed since the completion of the most
recent course of radiation therapy, the last dose of temozolomide (TMZ), or placement
of Gliadel wafers

- No prior cytotoxic therapies other than temozolomide and Gliadel wafers

- Prior anti-VEGF therapies are allowed if more than four months have elapsed from the
end of prior treatment

- 30 days must have elapsed since previous treatment of the brain tumor with any other
agents

- Must be maintained on a stable or decreasing corticosteroid regimen (no increase for
7 days) prior to the start of treatment

- Patients may not be receiving any other investigational agents or chemotherapeutic
agents other than temozolomide

- No anti-arrhythmia medication other than beta-blockers or digoxin

- No requirement for a calcium channel blocker for blood pressure control that cannot
be switched to an antihypertensive with an alternative mechanism of action

- Permitted anti-hypertensive medications include: chlorothiazide,
hydrochlorothiazide, atenolol, nadolol, enalapril, lisinopril, eprosartan, and
irbesartan

- Patients cannot receive any statin while on trial except pravastatin

- No treatment with an H2 blocker, other than famotidine

- If the patient requires a proton pump inhibitor (PPI), then esomeprazole,
pantoprazole, or rabeprazole may be given

- No concurrent enzyme-inducing anti-epileptic drugs (EIAEDs)

- Patients previously treated with EIAEDs may be enrolled if they have been off
the EIAED for 10 days or more prior to the first dose of mibefradil

- Patients taking an anticoagulant must use warfarin or a low molecular weight heparin

- Unfractionated heparin is not permitted

- No drugs that are substrates of CYP3A4, CYP2D6, and CYP1A2 except for the ones that
are explicitly permitted

- No drugs that have potential to interfere with metabolism or excretion of mibefradil

- Patients who are taking and cannot discontinue over-the-counter (OTC) medications and
nutritional supplements, including herbal or "Chinese" medications, are not eligible,
except for the following:

- OTC medications that are allowed at labeled doses during dosing with mibefradil
are acetaminophen, aspirin, diphenhydramine, calcium carbonate antacids, branded
multiple vitamin supplements and pseudoephedrine

- Topical preparations and decongestant nasal sprays are allowed