TAU-2014-1: Mibefradil and Hypofractionated Re-Irradiation Therapy in Recurrent GBM

Exclusion Criteria

• •Karnofsky performance status ≥60%
• •Clinical laboratory:
• •absolute neutrophil count \>1,500/microliter (mcL)
• •platelets \>100,000/mcL
• •hemoglobin \> 9 g/ dL serum bilirubin \< 1.5 times the upper limit of normal (ULN); unless due to Gilbert's syndrome (in which \<2 times ULN acceptable)
• •serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) \< 2.5 times ULN
• •serum Creatinine \< 1.5 times ULN
• •Women of childbearing potential and men must agree to use adequate contraception.
• •Women of childbearing potential must have a negative pregnancy test prior to treatment.
• •Recovered to Common Toxicity Criteria for Adverse Effects (CTCAE) grade ≤ 2 from prior therapy toxicities
• •30 days since previous treatment of brain tumor with any other agents.
• •Stable or decreasing corticosteroid regimen (no increase for 7 days) prior to the start of treatment.
• •\>18 years of age
• •Concurrent malignancy except curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix, breast, or bladder. Subjects with prior malignancies must be disease-free for ≥ five years.
• •Biopsy-confirmed exclusive radionecrosis after initial GBM therapy.
• •Receipt of other investigational agents or anti-cancer agents within 30 days
• •Serious concurrent infection or medical illness, which would jeopardize the ability of the subject to receive treatment safely.
• •Systolic blood pressure \<100 mm Hg, diastolic \<60 mm Hg.
• •Requirement for 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.
• •Known, active hepatitis.
• •corrected QT (QTc) interval ≥ 450 milliseconds (mSec) for males or ≥470 mSec for females. PR interval \> 250 mSec for males and females
• •High-grade (second degree or above) atria-ventricular (AV) block or persistent sinus bradycardia of less than 50 beats per minute (BPM).
• •Known HIV-positivity
• •Pregnant and/or lactating women
• •Anti-arrhythmia medication other than beta-blockers or digoxin.
• •Treatment with concurrent enzyme-inducing anti-epileptic drugs (EIAEDs).
• •Treatment with unfractionated heparin. Patients taking an anticoagulant must use warfarin or a low molecular weight heparin.
• •Treatment with specified drugs that are substrates of cytochrome 3A4 (CYP3A4), cytochrome 2D6 (CYP2D6), cytochrome 1A2 (CYP1A2)