Ignite Creation Date:
2025-12-24 @ 2:50 PM
Ignite Modification Date:
2025-12-25 @ 1:17 PM
Study NCT ID:
NCT04485559
Status:
RECRUITING
Last Update Posted:
2025-09-15
First Post:
2020-07-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Trametinib and Everolimus for Treatment of Pediatric and Young Adult Patients With Recurrent Gliomas (PNOC021)
Sponsor:
University of California, San Francisco
Organization:
Study Overview
Official Title:
PNOC021: A Phase I Trial Evaluating the Combination of Trametinib and Everolimus in Pediatric and Young Adult Patients With Recurrent Low-Grade Gliomas and High Grade Gliomas
Status:
RECRUITING
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial studies the side effects and best dose of trametinib and everolimus in treating pediatric and young adult patients with gliomas that have come back (recurrent). Trametinib acts by targeting a protein in cells called MEK and disrupting tumor growth. Everolimus is a drug that may block another pathway in tumor cells that can help tumors grow. Giving trametinib and everolimus may work better to treat low and high grade gliomas compared to trametinib or everolimus alone.
Detailed Description:
PRIMARY OBJECTIVES:
I. To estimate the recommended phase 2 dose (RP2D) of trametinib given orally in combination with everolimus in pediatric and young adult patients with gliomas.
II. To describe the toxicity profile and define the dose limiting toxicities (DLTs) of the combination of trametinib and everolimus in pediatric and young adult patients with recurrent low-grade gliomas (LGG) or high grade glioma (HGG).
III. To characterize the pharmacokinetic profile of trametinib and everolimus when given in combination.
EXPLORATORY OBJECTIVES:
I. To describe the objective response rate and the 2-year progression-free survival (PFS) of LGGs to this therapy in the context of a phase I study.
II. To assess quality of life (QOL) and cognitive measures in pediatric and young adult patients with LGG or HGG.
III. To identify potential predictive biomarkers to targeted therapy in pediatric and young adult patients with LGGs.
IV. To assess endocrine outcomes in pediatric and young adult patients with LGGs.
V. To explore magnetic resonance (MR) quantitative measures of relative cerebral blood volume, permeability and apparent diffusion coefficient within the region of hyperintensity 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).
OUTLINE: This is a dose-escalation study.
Patients receive a combination of trametinib orally (PO) and everolimus in either of two dosing scheduled (continuous and intermittent). Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, then every 6 months for 5 years from the start of therapy.
I. To estimate the recommended phase 2 dose (RP2D) of trametinib given orally in combination with everolimus in pediatric and young adult patients with gliomas.
II. To describe the toxicity profile and define the dose limiting toxicities (DLTs) of the combination of trametinib and everolimus in pediatric and young adult patients with recurrent low-grade gliomas (LGG) or high grade glioma (HGG).
III. To characterize the pharmacokinetic profile of trametinib and everolimus when given in combination.
EXPLORATORY OBJECTIVES:
I. To describe the objective response rate and the 2-year progression-free survival (PFS) of LGGs to this therapy in the context of a phase I study.
II. To assess quality of life (QOL) and cognitive measures in pediatric and young adult patients with LGG or HGG.
III. To identify potential predictive biomarkers to targeted therapy in pediatric and young adult patients with LGGs.
IV. To assess endocrine outcomes in pediatric and young adult patients with LGGs.
V. To explore magnetic resonance (MR) quantitative measures of relative cerebral blood volume, permeability and apparent diffusion coefficient within the region of hyperintensity 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).
OUTLINE: This is a dose-escalation study.
Patients receive a combination of trametinib orally (PO) and everolimus in either of two dosing scheduled (continuous and intermittent). Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, then every 6 months for 5 years from the start of therapy.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2020-04097 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View |