A Phase I Study of SAHA and Temozolomide in Children With Relapsed or Refractory Primary Brain or Spinal Cord Tumors
I. To estimate the maximum tolerated dose and/or recommended phase II dose of vorinostat in
combination with temozolomide in pediatric patients with relapsed or refractory primary CNS
II. To define and describe the toxicities of this regimen in these patients.
I. To preliminarily define the antitumor activity of this regimen within the confines of a
phase I study.
II. To characterize the pharmacokinetic parameters of vorinostat in these patients.
III. To determine whether acetylated histones in peripheral blood mononuclear cells can be
identified as a surrogate marker of the biologic effect of vorinostat at various treatment
IV. To assess the feasibility of collecting and analyzing serum DNA for methylation of the
MGMT promoter and describe the relationship between promoter methylation and clinical
responses within the confines of this phase I study.
OUTLINE: This is a multicenter, dose-escalation study of vorinostat.
Patients receive oral vorinostat and oral temozolomide once daily on days 1-5. Courses
repeat every 28 days for up to 13 courses in the absence of disease progression or
Patients may undergo blood sample collection periodically for pharmacokinetic and
correlative laboratory studies by western blotting and MGMT promoter methylation assays.
After completion of study therapy, patients are followed up for 30 days.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose defined as the maximum dose at which fewer than one-third of patients experience DLT using NCI CTCAE version 4.0
In addition to determination of the MTD, a descriptive summary of all toxicities will be reported.
COG Phase I Consortium
United States: Food and Drug Administration
|Baylor College of Medicine||Houston, Texas 77030|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|Oregon Health and Science University||Portland, Oregon 97201|
|Seattle Children's Hospital||Seattle, Washington 98105|
|Childrens Memorial Hospital||Chicago, Illinois 60614|
|University of Minnesota Medical Center-Fairview||Minneapolis, Minnesota 55455|
|C S Mott Children's Hospital||Ann Arbor, Michigan 48109|