Ph I Dose Escalation Trial of Vandetanib in Combo w Etoposide for Malignant Gliomas

Inclusion Criteria: Patients have baseline evaluations ≤14days prior to 1st dose of study drug unless otherwise specified * Patients with confirmed malignant glioma (MG) who are recurrence/relapse * Patients may not have stereotactic tumor biopsy \< 1 week or surgical resection or open biopsy \< 4 weeks before starting study drug * For stratum of non-EIAED patients, each patient must be off all EIAEDs for \> 2 weeks prior to starting study drug; similarly for stratum of EIAED patients, each patient must be on EIAED for \>2 weeks prior to starting study drug * Patients should be on non-increasing dose of steroids for \>7 days prior to obtaining baseline MRI with gadolinium (Gd-MRI) of brain * Patients should be on non-increasing dose of steroids for \>7 days prior to starting study drug * Multifocal disease is eligible * Age ≥ 18 years * Karnofsky Performance Status (KPS) ≥70 * Absolute Neutrophil Count ≥1.0 x 10 9/L * Hemoglobin (Hgb) ≥9 g/dL * Platelets ≥100 x 10 9/L * Serum creatinine ≤1.5 x ULRR or measured 24-hr CrCl ≥50mL/min/1.73m2 * Life expectancy ≥ 12 weeks * Written informed consent obtained prior to screening procedures * Negative Beta-HCG pregnancy test for women of child-bearing potential Exclusion Criteria: * Laboratory Results: * Serum direct bilirubin \>1.5 x upper limit of normal (ULN) of reference range * Serum creatinine \>1.5 x ULRR \& CrCl \<30 mL/min * Potassium, \<4.0 mmol/L despite supplementation; serum calcium, magnesium out of normal range despite supplementation * ALT or AST \> 2.5 x ULRR * Evidence of severe/uncontrolled systemic disease or any concurrent condition which in Investigator's opinion makes it undesirable for patient to participate in trial or which would jeopardize compliance with protocol * Clinically significant cardiovascular event such as myocardial infarction, superior vena cava syndrome, New York Heart Association classification of heart disease \>2 within 3 months before entry; or presence of cardiac disease that, in opinion of Investigator, increases risk of ventricular arrhythmia * History of arrhythmia which is symptomatic/requires treatment/asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded. * Previous history of QTc prolongation as result from other medication that required discontinuation of that medication * Congenital long QT syndrome, or 1st degree relative with unexplained sudden death \<40 years * Presence of left bundle branch block * QTc with Bazett's correction that's unmeasureable, or ≥ 480msec on screening EEG. * Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes/induce CYP3A4 function except for EIAEDs * Hypertension not controlled by medical therapy * Currently active diarrhea that may affect ability of patient to absorb study regimen/tolerate diarrhea * Women who are currently pregnant/breast feeding * Previous or current malignancies of other histologies the last year, with exception of cervical carcinoma in situ \& adequately treated basal cell or squamous cell carcinoma of skin * Receipt of any investigational agents \<30 days prior to commencing study treatment unless pt has recovered from all anticipated toxicities of investigational agent * Last dose of prior chemo discontinued \< 4 weeks before start of study therapy unless pt has recovered from all anticipated toxicities of chemo * Last XRT \< 4 weeks before start of study therapy, unless patient has recovered from all anticipated toxicities of XRT * Any unresolved toxicity \>CTC gr1 from previous anti-cancer therapy * Previous enrollment/randomization of treatment in present study * Major surgery \< 4 weeks/incompletely healed surgical incision before starting study therapy * Patients who have received prior oral VEGFR, EGFR or PDGFR-directed therapies. Patients who received prior Avastin will be eligible as long as at least 6 weeks has elapsed since last dose. * Patients taking warfarin sodium