Phase I Dose Escalation of Vandetanib (Zactima, ZD6474) in Combination With 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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety, tolerability, biologic activity, & pharmacokinetic profile of vandetanib when used in combo w etoposide
6-month progression free survival
Annick Desjardins, MD
Duke University Health System
United States: Food and Drug Administration
|Duke University Health System||Durham, North Carolina 27705|