Pharmacokinetics in Patients With Newly Diagnosed High-Grade Glioma Receiving Temozolomide and Radiation Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00471653
Recruitment Status : Unknown
Verified July 2009 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : May 10, 2007
Last Update Posted : November 9, 2009
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Studying samples of blood in the laboratory from patients receiving temozolomide may help doctors learn how temozolomide works in the body. It may also help doctors learn more about how a patient's genes may affect the risk of developing thrombocytopenia.

PURPOSE: This clinical trial is studying the pharmacokinetics in patients with newly diagnosed high-grade glioma receiving temozolomide and radiation therapy.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Thrombocytopenia Drug: temozolomide Genetic: comparative genomic hybridization Genetic: polymorphism analysis Other: laboratory biomarker analysis Other: pharmacological study Radiation: radiation therapy Not Applicable

Detailed Description:


  • Compare the pharmacokinetic (PK) profiles of temozolomide (TMZ) in patients who develop severe thrombocytopenia vs PK profiles in patients who do not develop severe thrombocytopenia while receiving standard first-line therapy for management of newly diagnosed high-grade gliomas.
  • Determine if patients who develop thrombocytopenia have any single nucleotide polymorphisms in the O6-methylguanine-DNA methyltransferase gene.

OUTLINE: This is a pilot, prospective, multicenter study.

Patients receive oral temozolomide once daily on days 1-42. Patients also undergo cranial radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for pharmacokinetic and pharmacogenomic analysis, genotype analysis, plasma temozolomide levels, and MGMT repair gene polymorphism analysis.

After completion of study treatment, patients are followed for 1 month.

PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Primary Purpose: Treatment
Official Title: A Pharmacokinetic and Pharmacogenomic Study of Patients With High-Grade Gliomas Receiving Daily Radiation Therapy and Temozolomide
Study Start Date : November 2006
Estimated Primary Completion Date : December 2008

Primary Outcome Measures :
  1. Correlation of pharmacokinetics with incidence of dose-limiting toxicities

Secondary Outcome Measures :
  1. Maximum concentration of temozolomide
  2. Polymorphisms in the MGMT repair gene

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed high-grade glioma (WHO grade III or IV)
  • Must be scheduled to receive standard first-line therapy (cranial radiotherapy and temozolomide)


  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Creatinine ≤ 1.7 mg/dL
  • Bilirubin ≤ 1.5 mg/dL
  • Transaminases ≤ 4 times upper limit of normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell carcinoma of the skin


  • No prior hormonal therapy for brain tumor
  • No prior biological agents (including immunotoxins, immunoconjugates, antisense agents, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cells, or gene therapy)
  • No prior immunotherapy
  • No prior chemotherapy
  • No prior radiotherapy, including cranial radiotherapy
  • Concurrent glucocorticoid therapy allowed
  • No concurrent carbamazepine
  • No other concurrent experimental therapy
  • No other concurrent cytotoxic therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00471653

United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
Study Chair: Stuart A. Grossman, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Identifier: NCT00471653     History of Changes
Other Study ID Numbers: CDR0000543866
First Posted: May 10, 2007    Key Record Dates
Last Update Posted: November 9, 2009
Last Verified: July 2009

Keywords provided by National Cancer Institute (NCI):
adult anaplastic oligodendroglioma
adult brain stem glioma
adult mixed glioma
adult giant cell glioblastoma
adult gliosarcoma
adult glioblastoma
adult anaplastic astrocytoma
adult anaplastic ependymoma
adult pineal gland astrocytoma

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Blood Platelet Disorders
Hematologic Diseases
Neoplasms by Site
Nervous System Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents