NCT01189266

Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

A Phase 1/2 Study of Suberoylanilide Hydroxamic Acid (SAHA, Vorinostat) and Local Irradiation, Followed by Maintenance SAHA in Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas (DIPG)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 79 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 37 Months – 21 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Anaplastic Astrocytoma
• Anaplastic Oligoastrocytoma
• Diffuse Intrinsic Pontine Glioma
• Gliosarcoma

Interventions

Type	Name	Description
RADIATION	3-Dimensional Conformal Radiation Therapy	Undergo 3D conformal radiation therapy
RADIATION	Intensity-Modulated Radiation Therapy	Undergo intensity-modulated radiation therapy
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Vorinostat	Given PO

Timeline

• Start date: 2010-08-09
• Primary completion: 2017-06-30
• Completion: 2021-09-30
• First posted: 2010-08-26
• Last updated: 2021-10-28
• Results posted: 2020-03-03

Locations

180 sites across 3 countries: United States, Australia, Canada