A Phase II Study of AZD2171 in Recurrent Glioblastoma
I. Determine the proportion of patients with recurrent glioblastoma multiforme (GM) who are
alive and progression free 6 months after starting AZD2171 therapy.
I. Assess the biological effect of AZD2171 by using the following MRI techniques: dynamic
contrast-enhanced imaging; arterial spin-labeling imaging; perfusion-weighted imaging; and
diffusion- tensor imaging at serial time points.
II. Measure circulating endothelial and progenitor cells and plasma levels of tumstatin,
(vascular endothelial growth factor (VEGF)-A and -D, sVEGF receptors, P1GF, platelet-derived
growth factor (PDGF)-AA, PDGF-AB, PDGF-BB, Ang1, thrombospondin-1, and interleukin-8 as
markers for response to antiangiogenic therapy in recurrent GM.
III. Correlate treatment outcomes with pre-AZD2171 tumor specimens with respect to
microvascular density, basement membrane and pericyte coverage, and angiopoietin-1 and -2
expression to determine whether these immunohistochemical analyses can be predictive of the
response to AZD2171.
IV. Measure polymorphisms of kdr/flk-1 gene and genetic analysis of HIF1-alpha, TP53, and
endothelial nitric oxide synthase genes in the archival tumor specimens.
V. Determine the overall survival of patients with recurrent GM treated with AZD2171.
VI. Determine the radiographic response rate in patients with recurrent GM treated with
VII. Determine the safety of AZD2171 in this patient population.
OUTLINE: This is a multicenter study.
Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for up to 12 months.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of patients alive and progression-free at 6 months
Massachusetts General Hospital
United States: Food and Drug Administration
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