Phase I study of ribociclib and everolimus in children with newly diagnosed DIPG and high-grade glioma: A CONNECT pediatric neuro-oncology consortium report.

ABSTRACT:

Background

Genomic aberrations in the cell cycle and PI3K/Akt/mTOR pathways have been reported in diffuse intrinsic pontine glioma (DIPG) and high-grade glioma (HGG). Dual inhibition of CDK4/6 and mTOR has biologic rationale and minimal overlapping toxicities. This study determined the recommended phase 2 dose (RP2D) of ribociclib and everolimus following radiotherapy in children with DIPG and HGG.

Methods

Patients were enrolled according to a Rolling-6 design and received ribociclib and everolimus once daily for 21 and 28 days, respectively. All patients with HGG and biopsied DIPG were screened for retinoblastoma protein presence by immunohistochemistry. Pharmacokinetics were analyzed.

Results

Nineteen patients enrolled (median age: 8 years [range: 2-18]). Thr

SUBMITTER: DeWire M 

PROVIDER: S-EPMC9122788 | biostudies-literature | 2022 Jan-Dec

REPOSITORIES: biostudies-literature