Everolimus (RAD001) for Children With Chemotherapy-Refractory Progressive or Recurrent Low-Grade Gliomas
|ClinicalTrials.gov Identifier: NCT00782626|
Recruitment Status : Completed
First Posted : October 31, 2008
Results First Posted : February 2, 2016
Last Update Posted : February 2, 2016
|Condition or disease||Intervention/treatment||Phase|
|Glioma Low-grade Glioma Astrocytoma||Drug: everolimus||Phase 2|
- 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.
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 (Clinical Trial)|
|Actual Enrollment :||23 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Everolimus (RAD001) for Children With Chemotherapy and/or Radiation-Refractory Progressive or Recurrent Low-Grade Gliomas|
|Study Start Date :||June 2009|
|Actual Primary Completion Date :||August 2012|
|Actual Study Completion Date :||August 2012|
Patients rcvd oral everolimus 5.0 mg/m2/day for a 28-day treatment course up to a total of 12 courses (48 weeks) if a patient had stable disease except if toxicity was unacceptable. Two dose reductions were permitted (3.0 5.0 mg/m2/day and 2.0 mg/m2/day).
Other Name: RAD001
- Overall Response [ 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. ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00782626
|United States, Arizona|
|Phoenix Children's Hospital Center for Cancer and Blood Disorders|
|Phoenix, Arizona, United States, 85016|
|United States, Colorado|
|The Children's Hospital|
|Denver, Colorado, United States, 80045|
|United States, Florida|
|University of Florida College of Medicine|
|Gainesville, Florida, United States, 32610|
|United States, Georgia|
|Children's Healthcare of Atlanta|
|Atlanta, Georgia, United States, 30322|
|United States, Maryland|
|John Hopkins Medical Center|
|Baltimore, Maryland, United States, 21231|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|New York University|
|New York, New York, United States, 10016|
|Memorial Sloan-Kettering Cancer Institute|
|New York, New York, United States, 10174|
|United States, Oregon|
|Doernbecher Children's Hospital Oregon Health & Science University|
|Portland, Oregon, United States, 97239|
|United States, Washington|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Mark W. Kieran, MD, PhD||Dana-Farber Cancer Institute|