Wee1 kinase inhibitor adavosertib with radiation in newly diagnosed diffuse intrinsic pontine glioma: A Children's Oncology Group phase I consortium study.

ABSTRACT:

Background

Children with diffuse intrinsic pontine gliomas (DIPG) have a dismal prognosis. Adavosertib (AZD1775) is an orally available, blood-brain barrier penetrant, Wee1 kinase inhibitor. Preclinical efficacy against DIPG is heightened by radiation induced replication stress.

Methods

Using a rolling six design, 7 adavosertib dose levels (DLs) (50 mg/m² alternating weeks, 50 mg/m² alternating with weeks of every other day, 50 mg/m², then 95, 130, 160, 200 mg/m²) were assessed. Adavosertib was only given on days of cranial radiation therapy (CRT).The duration of CRT (54 Gy over 30 fractions; 6 weeks) constituted the dose limiting toxicity (DLT) period. Endpoints included tolerability, pharmacokinetics, overall survival (OS) and pe

SUBMITTER: Mueller S 

PROVIDER: S-EPMC9209747 | biostudies-literature | 2022 Jan-Dec

REPOSITORIES: biostudies-literature