The purpose of this research study is to learn if the study drug RAD001 can shrink or slow the growth of low-grade gliomas. Additionally, the safety of RAD001 will be studied. RAD001 is a drug that may act directly on tumor cells by inhibiting tumor cell growth and proliferation.
OBJECTIVES: Primary * To determine the response of children with chemotherapy-refractory or progressive low-grade gliomas to everolimus. Secondary * To evaluate pharmacogenetic polymorphisms of cytochrome P450 3A4 \& 3A5 alleles and P-glycoprotein/MDR for their influence on the metabolism of everolimus in this patient population. * To evaluate the role of Apolipoprotein E genotypes as predictors for development of hyperlipidemia during therapy with everolimus. * To assess preliminary correlations of response with changes in pharmacodynamic parameters including p70s6 kinase activity in peripheral blood mononuclear cells. * To describe the toxicity of everolimus when administered to this patient population. * To characterize the pharmacokinetic profile of everolimus when administered to this patient population. STATISTICAL DESIGN: This study used a one-stage design to evaluate response to everolimus. If at least 3 responders are observed in 20 evaluable patients, then everolimus will be considered promising. If the true response rate is 5% (null hypothesis), the chance of concluding the treatment is active is 0.08 (Type I error). If the true response rate is 25% (alternative hypothesis), the chance of concluding the treatment is active is 0.91 (power).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
23
Phoenix Children's Hospital Center for Cancer and Blood Disorders
Phoenix, Arizona, United States
The Children's Hospital
Denver, Colorado, United States
University of Florida College of Medicine
Gainesville, Florida, United States
Overall Response
Overall response is classified as complete response (CR), partial response (PR), stable disease (SD) or Progressive Disease (PD) on therapy.Description: Overall response is classified as complete response (CR), partial response (PR), stable disease (SD) or Progressive Disease (PD) on therapy. Response for target lesions (up to5) is based on 3 dimensions with an elliptical model volume used: 0.5L\*W\*T; (L) tumor extent in plane perpendicular to the selected plane; (W) longest measurement of the tumor width; (T) transverse measurement perpendicular to the width. CR is disappearance all target and non-target lesions and no new lesions. PR is \>/= 65% decrease in sum of the products (referent baseline). PD 40% or more increase in any target lesion (referent smallest product observed on therapy). SD is none of the above. PR and SD classification as long as absent new lesions and unequivocal progression for non-target lesions else PD.
Time frame: Disease evaluations (MRI brain, including volumetric analysis) occurred at baseline, at the end of course 1, every 3 courses during treatment up to 12 courses and at early treatment discontinuation.
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