Dataset Information
A Phase I and Surgical Study of Ribociclib and Everolimus in Children with Recurrent or Refractory Malignant Brain Tumors: A Pediatric Brain Tumor Consortium Study.
Ontology highlight
ABSTRACT: Purpose
Genomic aberrations in cell cycle and PI3K pathways are commonly observed in pediatric brain tumors. This study determined the MTD/recommended phase II dose (RP2D) of ribociclib and everolimus and characterized single-agent ribociclib concentrations in plasma and tumor in children undergoing resection.Patients and methods
Patients were enrolled in the phase I study according to a rolling 6 design and received ribociclib and everolimus daily for 21 and 28 days, respectively. Surgical patients received ribociclib at the pediatric RP2D (350 mg/m2) for 7-10 days preoperatively followed by enrollment on the phase I study. Pharmacokinetics were analyzed for both cohorts.Results
Sixteen patients were enrolled on the phase I study (median age, 10.3 years; range, 3.9-20.4) and 6 patients in the surgical cohort (median age, 11.4 years; range: 7.2-17.1). Thirteen patients were enrolled at dose level 1 without dose-limiting toxicities (DLT). Two of the 3 patients at dose level 2 experienced DLTs (grade 3 hypertension and grade 4 alanine aminotransferase). The most common grade 3/4 toxicities were lymphopenia, neutropenia, and leukopenia. The RP2D of ribociclib and everolimus was 120 and 1.2 mg/m2 for 21 and 28 days, respectively. Steady-state everolimus exposures with ribociclib were 2.5-fold higher than everolimus administered alone. Ribociclib plasma, tumor concentrations, and cerebrospinal fluid (CSF) samples were collected. The mean tumor-to-plasma ratio of ribociclib was 19.8 (range, 2.22-53.4).Conclusions
Ribociclib and everolimus were well-tolerated and demonstrated pharmacokinetic properties similar to those in adults. Potential therapeutic ribociclib concentrations could be achieved in CSF and tumor tissue, although interpatient variability was observed.
SUBMITTER: DeWire MD
PROVIDER: S-EPMC8132306 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
A Phase I and Surgical Study of Ribociclib and Everolimus in Children with Recurrent or Refractory Malignant Brain Tumors: A Pediatric Brain Tumor Consortium Study.
Clinical cancer research : an official journal of the American Association for Cancer Research 20210205 9
<h4>Purpose</h4>Genomic aberrations in cell cycle and PI3K pathways are commonly observed in pediatric brain tumors. This study determined the MTD/recommended phase II dose (RP2D) of ribociclib and everolimus and characterized single-agent ribociclib concentrations in plasma and tumor in children undergoing resection.<h4>Patients and methods</h4>Patients were enrolled in the phase I study according to a rolling 6 design and received ribociclib and everolimus daily for 21 and 28 days, respectivel ...[more]