Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma
Condition: Anaplastic Astrocytoma; Anaplastic Oligoastrocytoma; Diffuse Intrinsic Pontine Glioma; Gliosarcoma
MeSH terms: Glioma; Astrocytoma; Gliosarcoma; Diffuse Intrinsic Pontine Glioma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This phase I/II trial studies the side effects and best dose of vorinostat and to see how
      well it works when given together with radiation therapy followed by maintenance therapy with
      vorinostat in treating younger patients with newly diagnosed diffuse intrinsic pontine glioma
      (a brainstem tumor). Vorinostat may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor
      cells. Giving vorinostat together with radiation therapy may kill more tumor cells.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      l. To estimate the maximum tolerated dose (MTD) or recommend a phase 2 dose of vorinostat
      given concurrently with radiation in children with newly diagnosed diffuse intrinsic pontine
      glioma (DIPG).

      II. To define and describe the toxicities of vorinostat given concurrently with radiation in
      children with newly diagnosed DIPG.

      III. To determine, in the context of this phase I/II trial, the anti-tumor activity of
      combining vorinostat with radiation, followed by maintenance vorinostat for twelve courses,
      in children with newly diagnosed DIPG, as measured by 12-month event-free survival (EFS) and
      overall survival (OS).

      IV. To determine the toxicities of vorinostat for 12 additional courses after completion of
      vorinostat and radiation.

      SECONDARY OBJECTIVES:

      I. To measure non-homologous end-joining (NHEJ) activity in peripheral blood mononuclear
      cells (PBMCs) before treatment, at 2 weeks after starting vorinostat and radiation, and at
      the end of radiation.

      II. To measure histone deacetylase 2 (HDAC2) levels and assess histone acetylation in PBMCs
      before treatment, at 2 weeks after starting vorinostat and radiation, and at the end of
      radiation.

      III. To quantify deoxyribonucleic acid (DNA) repair proteins from the NHEJ and homologous
      recombination repair (HHR) pathways in tumors by either Western analysis or
      immunohistochemistry, if paraffin-embedded tumor is available.

      OUTLINE: This is a phase I, dose-escalation study of vorinostat followed by a phase II study.

      Patients receive vorinostat orally (PO) on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40.
      Patients undergo 3-dimensional (3D) conformal or intensity-modulated radiation therapy 5 days
      per week for 6 weeks. Patients then receive maintenance therapy comprising vorinostat PO on
      days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48,
      and 60 months.
    

Intervention name(s): 3-Dimensional Conformal Radiation Therapy; Intensity-Modulated Radiation Therapy; Laboratory Biomarker Analysis; Vorinostat
Intervention type(s): Radiation; Radiation; Other; Drug
Intervention description(s): Undergo 3D conformal radiation therapy; Undergo intensity-modulated radiation therapy; Correlative studies; Given PO
Other intervention name(s): 3-dimensional radiation therapy; 3D Conformal; 3D CONFORMAL RADIATION THERAPY; 3D CRT; 3D-CRT; Conformal Therapy; Radiation Conformal Therapy; Radiation, 3D Conformal; IMRT; Intensity Modulated RT; Intensity-Modulated Radiotherapy; Radiation, Intensity-Modulated Radiotherapy; L-001079038; MSK-390; SAHA; Suberanilohydroxamic Acid; Suberoylanilide Hydroxamic Acid; Zolinza
Intervention MeSH terms: Vorinostat
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment