Phase I trial of MK-0752 in children with refractory CNS malignancies: a pediatric brain tumor consortium study.

ABSTRACT:

Purpose

To estimate the maximum-tolerated dose (MTD), describe dose-limiting toxicities (DLTs), and characterize pharmacokinetic properties of MK-0752, a gamma secretase inhibitor, in children with refractory or recurrent CNS malignancies.

Patients and methods

MK-0752 was administered once daily for 3 consecutive days of every 7 days at escalating dosages starting at 200 mg/m(2). The modified continual reassessment method was used to estimate the MTD. A course was 28 days in duration. Pharmacokinetic analysis was performed during the first course. Expression of NOTCH and hairy enhancer of split (HES) proteins was assessed in peripheral-blood mononuclear cells (PBMCs) before and following treatment with MK-0752.

Results

Twenty-three eligible patients were enrolled: 10

SUBMITTER: Fouladi M 

PROVIDER: S-EPMC3179253 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature