Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors
Condition: 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
MeSH terms: Neoplasms; Glioma; Neoplasms, Germ Cell and Embryonal; Astrocytoma; Meningioma; Ependymoma; Medulloblastoma; Oligodendroglioma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Teratoma; Endodermal Sinus Tumor; Paraganglioma; Choriocarcinoma; Rhabdoid Tumor; Craniopharyngioma; Adamantinoma; Choroid Plexus Neoplasms; Pinealoma; Glioblastoma; Spinal Cord Neoplasms; Germinoma; Paraganglioma, Extra-Adrenal; Recurrence
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): vorinostat; temozolomide; diagnostic laboratory biomarker analysis; pharmacological study
Intervention type(s): Drug; Drug; Other; Other
Other intervention name(s): L-001079038; SAHA; suberoylanilide hydroxamic acid; Zolinza; SCH 52365; Temodal; Temodar; TMZ; pharmacological studies
Intervention MeSH terms: Temozolomide; Vorinostat
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment