PNOC 001: Phase II Study of Everolimus for Recurrent or Progressive Low-grade Gliomas in Children
This is an open label study of everolimus in children with recurrent or progressive low-grade glioma.
Pediatric Recurrent Progressive Low-grade Gliomas
Pediatric Progressive Low-grade Gliomas
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||PNOC 001: Phase II Study of Everolimus for Recurrent or Progressive Low-grade Gliomas in Children|
- Evaluation of efficacy by Progression Free Survival associated with everolimus therapy [ Time Frame: up to 6 months ] [ Designated as safety issue: No ]Determined by 6-month progression free survival. Response will be determined by bi-dimensional diameters. RECIST criteria will be collected and used for secondary evaluation. Patients will have brain MRI scans with and without gadolinium performed prior to therapy, after every second course in the first year, after every third course in the second year, and at the End of Study visit (if not done within prior 3 months). Spine MRIs should be performed prior to therapy and at the same time points as standard brain MRIs if clinically indicated.
- Estimation of Objective Response - Progression Free Survival [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]Estimate Progression Free Survival distribution along with objective response rates associated with everolimus treatment.
- Exploration of Associations with pS6 Positivity and Outcome [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]Explore associations between pS6 positivity and outcome as measured by the 6-month disease stabilization rates and Progession Free Survival.
- Estimation of Objective Response - Overall Survival [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]Estimate Overall Survival distributions along with objective response rates associated with everolimus treatment.
- Tissue Collection [ Time Frame: Up to 8 Years ] [ Designated as safety issue: No ]Collect tissue from ALL enrolled patients and prospectively analyze key molecular features including activation of the PI3K, mTOR and MAPK pathways, aberrations in PTEN, IDH1, and IDH2, and activating mutations in BRAF (KIAA1549-BRAF fusion and BRAFV600E missense BRAF mutation).
- Quantitative measures of cerebral blood [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]Explore MR quantitative measures of relative cerebral blood volume, permeability and apparent diffusion coefficient within the region of hyper-intensity on T2-weighted images as markers of disease response and/or progression in comparison to institutional evaluation of disease response and/or progression and quantitative measures of tumor response as determined by central review (based upon both area and volumetric measures.
|Study Start Date:||November 2012|
|Estimated Study Completion Date:||November 2022|
|Estimated Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
Everolimus tablet will be taken daily by mouth with water. Twenty-eight days will constitute one course and subsequent courses will immediately follow with no break in the administration of the drug. Dosing is based on the BSA (body surface area) calculated at the beginning of each course of therapy. Patients will also be provided with a drug diary for everolimus. The maximum time on study is 24-months, but if there is no disease progression or adverse events, the patient may speak with a doctor about continuing the treatment off-study.
Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.
This is an open label study of everolimus in children with recurrent or progressive low-grade glioma. All patients will receive everolimus at a dose of 5 mg/m2/dose daily. An adaptive Simon two-stage design for phase 2 studies of targeted therapies will be used to assess the efficacy primary objective. The proposed treatment with everolimus will be deemed not worthy of further investigation in this patient population if the true PFS at 6-months (PFS6) is less than 50%. If in the first stage, with a combined sample size of 25, there is preliminary evidence to suggest efficacy of everolimus is restricted to patients with PI3K/AKT/mTOR activation as measured by p-S6 positivity, a total of 45 patients will be enrolled and the design will have 81% statistical power to detect a true disease stabilization rate ≥70%. If in the first stage there is preliminary evidence to suggest efficacy of everolimus is independent of PI3K/AKT/mTOR activation, a total of 65 patients will be enrolled and the design will have >95% statistical power to detect a true disease stabilization rate ≥70%.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01734512
|Contact: Sharon Kresge||415-514-3658||LeeSS@peds.ucsf.edu|
|United States, California|
|University of California, Los Angeles||Not yet recruiting|
|Los Angeles, California, United States, 90027|
|Contact: Tom B Davidson, MD 310-825-6708 email@example.com|
|Principal Investigator: Tom B Davidson, MD|
|Children's Hospital Los Angeles||Not yet recruiting|
|Los Angeles, California, United States, 90027|
|Contact: Ghirish Dhall, MD 323-361-8147 GDhall@chla.usc.edu|
|Contact: Jonathan Finlay, MD 323-361-8147 JFinlay@chla.usc.edu,|
|Principal Investigator: Ghirish Dhall, MD|
|Sub-Investigator: Jonathan Finlay, MD|
|Children's Hospital Oakland||Not yet recruiting|
|Oakland, California, United States, 94609|
|Contact: Joseph Torkildson, MD 510-428-3272 firstname.lastname@example.org|
|Contact: Caroline Hastings, MD (510) 428-3272 email@example.com|
|Principal Investigator: Joseph Torkildson, MD|
|Sub-Investigator: Caroline Hastings, MD|
|University of California, San Diego Rady Children's Hospital||Not yet recruiting|
|San Diego, California, United States, 92123|
|Contact: John Crawford, MD 858-966-4930 firstname.lastname@example.org|
|Contact: Michael Levy, MD (858) 966 4930 email@example.com|
|Principal Investigator: John Crawford, MD|
|Sub-Investigator: Michael Levy, MD|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94115|
|Contact: Daphne Haas-Kogan, MD 415-353-7187 firstname.lastname@example.org|
|Contact: Sabine Mueller, MD 415-476-3831 email@example.com|
|Sub-Investigator: Sabine Mueller, MD|
|Principal Investigator: Daphne Haas-Kogan, MD|
|Sub-Investigator: Michael Prados, MD|
|United States, Oregon|
|Oregon Health & Science University||Recruiting|
|Portland, Oregon, United States, 97239|
|Contact: Kellie Nazemi, MD 503-494-1543 firstname.lastname@example.org|
|Principal Investigator: Kellie Nazemi, MD|
|United States, Utah|
|University of Utah||Recruiting|
|Salt Lake City, Utah, United States, 84112|
|Contact: Richard Lemons, MD 801-662-4700 email@example.com|
|Contact: Carol Bruggers, MD 801-662-4700 firstname.lastname@example.org|
|Principal Investigator: Richard Lemons, MD|
|Sub-Investigator: Carol Bruggers, MD|
|United States, Washington|
|University of Washington, Seattle||Not yet recruiting|
|Seattle, Washington, United States, 98195|
|Contact: Sarah Leary, MD 206-667-7955 email@example.com|
|Contact: Russ Geyer, MD 206-667-7955 firstname.lastname@example.org|
|Principal Investigator: Sarah Leary, MD|
|Sub-Investigator: Russ Geyer, MD|
|Study Chair:||Daphne Haas-Kogan, MD||University of California, San Francisco|
|Principal Investigator:||Daphne Haas-Kogan, MD||University of California, San Francisco|