Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma

OBJECTIVES:

Primary

- 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.

- To define and describe the toxicities of this regimen in these patients.

- To characterize the pharmacokinetics of this regimen in these patients.

Secondary

- To preliminarily define the antitumor activity of this regimen within the confines of a
phase I study.

- To assess the biologic activity of bortezomib by measuring NF-κB activity in peripheral
blood mononuclear cells (PBMC).

- 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.