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