PNOC 001: Phase II Study of Everolimus for Recurrent or Progressive Low-grade Gliomas in Children
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|ClinicalTrials.gov Identifier: NCT01734512|
Recruitment Status : Active, not recruiting
First Posted : November 27, 2012
Last Update Posted : March 27, 2020
|Condition or disease||Intervention/treatment||Phase|
|Pediatric Recurrent Progressive Low-grade Gliomas Pediatric Progressive Low-grade Gliomas||Drug: Everolimus||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||66 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||PNOC 001: Phase II Study of Everolimus for Recurrent or Progressive Low-grade Gliomas in Children|
|Actual Study Start Date :||December 13, 2012|
|Actual Primary Completion Date :||January 31, 2020|
|Estimated Study Completion Date :||January 31, 2028|
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 body surface area (BSA) 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.
- Evaluation of efficacy by Progression Free Survival associated with everolimus therapy [ Time Frame: up to 6 months ]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 ]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 ]Explore associations between pS6 positivity and outcome as measured by the 6-month disease stabilization rates and Progression Free Survival.
- Estimation of Objective Response - Overall Survival [ Time Frame: Up to 6 weeks ]Estimate Overall Survival distributions along with objective response rates associated with everolimus treatment.
- Tissue Collection [ Time Frame: Up to 8 Years ]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 ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01734512
|Study Chair:||Daphne Haas-Kogan, MD||Harvard University Dana-Farber Institute|
|Principal Investigator:||Sabine Mueller, MD||University of California, San Francisco|