A Phase I Study of Vorinostat and Bortezomib in Children With Refractory or Recurrent Solid Tumors, Including CNS Tumors and Lymphomas
Overview
- Phase
- Phase 1
- Intervention
- bortezomib
- Conditions
- Childhood Burkitt Lymphoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 20
- Locations
- 6
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed solid tumors, including CNS tumors or lymphoma
- •Histological confirmation not required for the following diagnoses
- •Intrinsic brain stem tumors
- •Optic pathway gliomas
- •Pineal tumors and elevations of cerebral spinal fluid or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin, allowed
- •Relapsed or refractory disease
- •Must have measurable or evaluable tumor
- •No known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- •Karnofsky performance status (PS) 60-100% for patients \> 16 years of age OR Lansky PS60-100% for patients ≤ 16 years of age
- •Neurologic deficits inpatients with CNS tumors must have been relatively stable for a minimum of 1week
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (vorinostat, bortezomib)
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.
Intervention: bortezomib
Treatment (vorinostat, bortezomib)
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.
Intervention: vorinostat
Treatment (vorinostat, bortezomib)
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.
Intervention: pharmacological study
Treatment (vorinostat, bortezomib)
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.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Disease response assessed according to RECIST criteria(Up to 30 days)