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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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 Summary:

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 fol
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Maximum tolerated dose defined as the maximum dose at which fewer than one-third of patients experience DLT using NCI CTCAE version 4.0 [ Time Frame: 28 days ]
    In addition to determination of the MTD, a descriptive summary of all toxicities will be reported.
  • Pharmacokinetic parameters of vorinostat in combination with temozolomide [ Time Frame: Pre-dose, 15 and 30 minutes, 1, 2, 4, 6, 8, and 24 hours ]
    The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).


Original Primary Outcome:

  • Maximum tolerated dose and/or recommended phase II dose of vorinostat in combination with temozolomide
  • Toxicity
  • Pharmacokinetic parameters of vorinostat in combination with temozolomide


Current Secondary Outcome: Response assessed according to RECIST criteria [ Time Frame: Up to 30 days ]

Will be reported descriptively.


Original Secondary Outcome: Response according to RECIST criteria

Information By: National Cancer Institute (NCI)

Dates:
Date Received: February 25, 2010
Date Started: February 2010
Date Completion:
Last Updated: May 1, 2013
Last Verified: May 2013