Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma
|ClinicalTrials.gov Identifier: NCT00994500|
Recruitment Status : Completed
First Posted : October 14, 2009
Last Update Posted : July 2, 2013
|Condition or disease||Intervention/treatment||Phase|
|Childhood Burkitt Lymphoma Childhood Central Nervous System Choriocarcinoma Childhood Central Nervous System Germ Cell Tumor Childhood Central Nervous System Germinoma Childhood Central Nervous System Mixed Germ Cell Tumor Childhood Central Nervous System Teratoma Childhood Central Nervous System Yolk Sac Tumor Childhood Choroid Plexus Tumor Childhood Craniopharyngioma Childhood Diffuse Large Cell Lymphoma Childhood Immunoblastic Large Cell Lymphoma Childhood Medulloepithelioma Childhood Meningioma Childhood Mixed Glioma Childhood Nasal Type Extranodal NK/T-cell Lymphoma Childhood Oligodendroglioma Recurrent Childhood Anaplastic Large Cell Lymphoma Recurrent Childhood Brain Stem Glioma Recurrent Childhood Central Nervous System Embryonal Tumor Recurrent Childhood Cerebellar Astrocytoma Recurrent Childhood Cerebral Astrocytoma Recurrent Childhood Ependymoma Recurrent Childhood Grade III Lymphomatoid Granulomatosis Recurrent Childhood Large Cell Lymphoma Recurrent Childhood Lymphoblastic Lymphoma Recurrent Childhood Malignant Germ Cell Tumor Recurrent Childhood Medulloblastoma Recurrent Childhood Pineoblastoma Recurrent Childhood Small Noncleaved Cell Lymphoma Recurrent Childhood Subependymal Giant Cell Astrocytoma Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor Recurrent Childhood Visual Pathway and Hypothalamic Glioma Recurrent Childhood Visual Pathway Glioma Recurrent/Refractory Childhood Hodgkin Lymphoma Unspecified Childhood Solid Tumor, Protocol Specific||Drug: vorinostat Drug: bortezomib Other: pharmacological study Other: laboratory biomarker analysis||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Vorinostat and Bortezomib in Children With Refractory or Recurrent Solid Tumors, Including CNS Tumors and Lymphomas|
|Study Start Date :||August 2009|
|Primary Completion Date :||July 2011|
Experimental: 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.
Other Names:Drug: bortezomib
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
- 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.
- Disease response assessed according to RECIST criteria [ Time Frame: Up to 30 days ]Will be reported descriptively.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00994500
|United States, Illinois|
|Childrens Memorial Hospital|
|Chicago, Illinois, United States, 60614|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh of UPMC|
|Pittsburgh, Pennsylvania, United States, 15224|
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jodi Muscal||COG Phase I Consortium|