NCT01076530

Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors

A Phase I Study of SAHA and Temozolomide in Children With Relapsed or Refractory Primary Brain or Spinal Cord Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial is studying the side effects and best dose of vorinostat when given together with temozolomide in treating young patients with relapsed or refractory primary brain tumors or spinal cord tumors. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may help temozolomide work better by making tumor cells more sensitive to the drug.

Detailed description

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose and/or recommended phase II dose of vorinostat in combination with temozolomide in pediatric patients with relapsed or refractory primary CNS tumors. II. To define and describe the toxicities 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 characterize the pharmacokinetic parameters of vorinostat in these patients. III. To determine whether acetylated histones in peripheral blood mononuclear cells can be identified as a surrogate marker of the biologic effect of vorinostat at various treatment doses. IV. To assess the feasibility of collecting and analyzing serum DNA for methylation of the MGMT promoter and describe the relationship between promoter methylation and clinical responses within the confines of this phase I study. OUTLINE: This is a multicenter, dose-escalation study of vorinostat. Patients receive oral vorinostat and oral temozolomide once daily on days 1-5. Courses repeat every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo blood sample collection periodically for pharmacokinetic and correlative laboratory studies by western blotting and MGMT promoter methylation assays. After completion of study therapy, patients are followed up for 30 days.

Conditions

• Childhood Atypical Teratoid/Rhabdoid Tumor
• Childhood Central Nervous System Choriocarcinoma
• Childhood Central Nervous System Embryonal 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 Ependymoblastoma
• Childhood Grade I Meningioma
• Childhood Grade II Meningioma
• Childhood Grade III Meningioma
• Childhood High-grade Cerebellar Astrocytoma
• Childhood High-grade Cerebral Astrocytoma
• Childhood Infratentorial Ependymoma
• Childhood Low-grade Cerebellar Astrocytoma
• Childhood Low-grade Cerebral Astrocytoma
• Childhood Medulloepithelioma
• Childhood Mixed Glioma
• Childhood Oligodendroglioma
• Childhood Supratentorial Ependymoma
• Extra-adrenal Paraganglioma
• 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 Medulloblastoma
• Recurrent Childhood Pineoblastoma
• Recurrent Childhood Spinal Cord Neoplasm
• Recurrent Childhood Subependymal Giant Cell Astrocytoma
• Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor
• Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Interventions

Type	Name	Description
DRUG	vorinostat
DRUG	temozolomide
OTHER	diagnostic laboratory biomarker analysis
OTHER	pharmacological study

Timeline

• Start date: 2010-02-01
• Primary completion: 2012-10-01
• First posted: 2010-02-26
• Last updated: 2013-05-03

Locations

9 sites across 2 countries: United States, Canada