A Phase I Study of Vorinostat and Bortezomib in Children With Refractory or Recurrent Solid Tumors, Including CNS Tumors and Lymphomas
I. To determine the maximum-tolerated dose and/or recommended phase II dose of vorinostat in
combination with bortezomib in pediatric patients with refractory or recurrent solid tumors,
including central nervous system tumors and lymphoma.
II. To define and describe the toxicities of this regimen in these patients. III. To
characterize the pharmacokinetics 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 assess the biologic activity of bortezomib by measuring NF-κB activity in peripheral
blood mononuclear cells (PBMC).
III. To assess the biologic activity of bortezomib by measuring endoplasmic reticulum stress
response using the GRP78 molecular chaperone marker in PBMC.
OUTLINE: This is a multicenter, dose-escalation study of vorinostat.
Patients receive oral vorinostat once daily on days 1-5 and 8-12 and bortezomib IV over 3-5
seconds on days 1, 4, 8, and 11. Courses repeat every 21 days for up to 2 years in the
absence of disease progression or unacceptable toxicity. Blood samples are collected at
baseline and during course 1 of study for further analysis.
After completion of study therapy, patients are followed up within 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 according to NCI CTCAE version 3.0
In addition to determination of the MTD, a descriptive summary of all toxicities will be reported.
Children's Oncology Group
United States: Food and Drug Administration
|Baylor College of Medicine||Houston, Texas 77030|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|Children's Hospital of Pittsburgh of UPMC||Pittsburgh, Pennsylvania 15213|
|Childrens Memorial Hospital||Chicago, Illinois 60614|
|Columbia University Medical Center||New York, New York 10032|