biostudies-literatureFouladi MNCI NIH HHS3529-34https://www.ebi.ac.uk/biostudies/studies/S-EPMC3179253biostudies-literatureUnknown29(26)<h4>Purpose</h4>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.<h4>Patients and methods</h4>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.<h4>Results</h4>Twenty-three eligible patients were enrolled: 10 Journal of clinical oncology : official journal of the American Society of Clinical OncologyPhase I trial of MK-0752 in children with refractory CNS malignancies: a pediatric brain tumor consortium study.PMC3179253U01 CA081457U01 CA81457Boyett JMPacker RJGilbertson RJOnar-Thomas AKocak MKun LEWagner LMGururangan SFouladi MGajjar AStewart CFGoldman SDemuth TOlson JfalsePhase I trial of MK-0752 in children with refractory CNS malignancies: a pediatric brain tumor consortium study.<h4>Purpose</h4>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.<h4>Patients and methods</h4>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.<h4>Results</h4>Twenty-three eligible patients were enrolled: 10 2011-01-01T00:00:00Z2011 Sep2025-04-26T03:16:55.316Z2019-03-26T23:49:33ZS-EPMC31792532182526410.1200/jco.2011.35.780610.1200/JCO.2011.35.7806