A Phase II Study of AZD2171 in Adult Patients With Neurofibromatosis Type 1 and Extensive Plexiform and Paraspinal Neurofibromas
I. Assess the efficacy of AZD2171, in terms of volume change in target tumors by
3-dimensional magnetic resonance imaging (3D MRI).
II. Describe and define the toxicities of AZD2171 in these patients.
I. Assess the value of 3D MRI data analysis in evaluating plexiform or paraspinal
neurofibromas compared to conventional 2-dimensional MRI data analysis.
II. Assess the value of delayed contrast-enhanced MRI (DCE-MRI) in determining changes in
vascularity of neurofibromas before and during treatment. III. Assess the quality of life
of patients treated with AZD2171. IV. Evaluate the effect of AZD2171 on biological changes
of human neurofibroma by comparing pre- and post-treatment specimens from patients involved
in this trial or, alternatively, by evaluating the effect of AZD2171 on human tumor grafts
in experimental animals.
V. Evaluate relevant pharmacodynamic markers (circulating endothelial cells [CECs] and
vascular endothelial growth factor-2 [VEGF2] levels) and pharmacogenetics analyses
(variation in kdr/flk-1 and other genes) in response to AZD2171.
OUTLINE: This is a multicenter study. Patients are stratified according to tumor location
(peripheral vs paraspinal plexiform neurofibroma). Patients receive oral AZD2171 once daily
on days 1-28.
Treatment repeats every 28 days for 26 courses in the absence of disease progression or
unacceptable toxicity. Patients with responding or stable disease may continue treatment
beyond 26 courses in the absence of disease progression or unacceptable toxicity. Quality of
life is assessed at baseline, prior to course 2, prior to course 4, and every 6 courses
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of confirmed tumor response (complete response [CR] or partial response [PR])
Decision Rule: The largest success proportion where the proposed treatment regimen would be considered ineffective in this population is 5% (i.e. null hypothesis). Conversely, the smallest success proportion that would warrant subsequent studies with the proposed regimen in this patient population is 15%. The null hypothesis is that the true success proportion in a given patient population is at most 5%. A maximum of 60 evaluable patients can be used to test the null hypothesis with this two-stage Simon design with modifications consistent with a Fleming design.
Baseline to end of treatment
United States: Food and Drug Administration
|Howard University Hospital||Washington, District of Columbia 20060|
|Mayo Clinic||Rochester, Minnesota 55905|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|Massachusetts General Hospital Cancer Center||Boston, Massachusetts 02114|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|University of Alabama at Birmingham||Birmingham, Alabama 35294-3300|
|Case Western Reserve University||Cleveland, Ohio 44106|
|Wayne State University||Detroit, Michigan 48202|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|