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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I Study of Vorinostat and Bortezomib in Children With Refractory or Recurrent Solid Tumors, Including CNS Tumors and Lymphomas

Brief Summary: This phase I trial is studying the side effects and best dose of vorinostat when given together with bortezomib in treating young patients with refractory or recurrent solid tumors, including CNS tumors and lymphoma. Vorinostat and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Detailed Summary:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: 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 [ Time Frame: 21 days ]

In addition to determination of the MTD, a descriptive summary of all toxicities will be reported.


Original Primary Outcome:

  • Maximum-tolerated dose of vorinostat in combination with bortezomib
  • Toxicity
  • Pharmacokinetics


Current Secondary Outcome: Disease response assessed according to RECIST criteria [ Time Frame: Up to 30 days ]

Will be reported descriptively.


Original Secondary Outcome:

  • Response (complete response, partial response, stable disease, or progressive disease)
  • Biologic activity of bortezomib


Information By: National Cancer Institute (NCI)

Dates:
Date Received: October 10, 2009
Date Started: August 2009
Date Completion:
Last Updated: July 1, 2013
Last Verified: July 2013