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

This is open-label, single center, 2-cohort phase I dose-escalation study of vandetanib administered orally on continuous daily dosing schedule + oral etoposide among adult patients with recurrent or relapsing malignant glioma. Patients will be stratified based on whether they are receiving EIAEDs \& each stratum will independently dose escalate. Dose of vandetanib will be increased in successive cohorts of patients. Etoposide will be given daily at a dose of 50mg/day for 21 days followed by 7 days with no etoposide. Cohorts of 3-6 subjects will accrue at each dose level until maximum tolerated dose (MTD) is defined. Subjects will be adult patients with histologically confirmed malignant glioma who are presenting at time of recurrence/relapse. Up to 48 subjects will be enrolled. Sample size will be based on modified, classical "3+3" dose escalation design. Primary safety \& efficacy analysis will be conducted on all subject data at time all subjects who are still receiving study drug will have completed at least 4 cycles of treatment. Most common adverse events (AEs) associated with vandetanib are rash, diarrhea, \& asymptomatic QTc prolongation. Protracted oral dosing of etoposide is associated with toxicity that is mild in most patients \& consists mainly of myelosuppression \& diarrhea. Less commonly, protracted etoposide dosing has been associated w more significant hematologic toxicity.