Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma
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
Description
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.
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Childhood Burkitt Lymphoma
Intervention
vorinostat, bortezomib, pharmacological study, laboratory biomarker analysis
Location
Childrens Memorial Hospital
Chicago
Illinois
United States
60614
Status
Active, not recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00994500
- Information obtained from ClinicalTrials.gov on February 11, 2013
Medical and Biotech [MESH] Definitions
Matched-pair Analysis
A type of analysis in which subjects in a study group and a comparison group are made comparable with respect to extraneous factors by individually pairing study subjects with the comparison group subjects (e.g., age-matched controls).
Costs And Cost Analysis
Absolute, comparative, or differential costs pertaining to services, institutions, resources, etc., or the analysis and study of these costs.
Multivariate Analysis
A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables.
Proportional Hazards Models
Statistical models used in survival analysis that assert that the effect of the study factors on the hazard rate in the study population is multiplicative and does not change over time.
Biotechnology
Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., GENETIC ENGINEERING) is a central focus; laboratory methods used include TRANSFECTION and CLONING technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction.
Clinical Trials
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PubMed Articles
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