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

Sponsors and Collaborators:	Sidney Kimmel Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00471653

Purpose

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	Intervention
Brain and Central Nervous System Tumors Cancer-Related Problem/Condition	Drug: temozolomide Procedure: comparative genomic hybridization Procedure: laboratory biomarker analysis Procedure: pharmacological study Procedure: polymorphism analysis Procedure: radiation therapy

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Pharmacokinetic and Pharmacogenomic Study of Patients With High-Grade Gliomas Receiving Daily Radiation Therapy and Temozolomide

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Correlation of pharmacokinetics with incidence of dose-limiting toxicities [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Maximum concentration of temozolomide [ Designated as safety issue: No ]
Polymorphisms in the MGMT repair gene [ Designated as safety issue: No ]

Estimated Enrollment:	150
Study Start Date:	November 2006
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00471653

Locations

United States, California
City of Hope Comprehensive Cancer Center	Recruiting
Duarte, California, United States, 91010-3000
Contact: Clinical Trials Office - City of Hope Comprehensive Cancer Cen 800-826-4673 becomingapatient@coh.org
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce 410-955-8804 jhcccro@jhmi.edu

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Stuart A. Grossman, MD

Sidney Kimmel Comprehensive Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000543866, JHOC-J0684, JHOC-NA_00004964
Study First Received:	May 8, 2007
Last Updated:	November 20, 2008
ClinicalTrials.gov Identifier:	NCT00471653
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

thrombocytopenia
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

Study placed in the following topic categories:

Glioblastoma
Astrocytoma
Central Nervous System Neoplasms
Temozolomide
Ependymoma
Neuroectodermal Tumors
Thrombocytopenia

Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Oligodendroglioma
Glioma
Gliosarcoma
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Nervous System Diseases
Neoplasms, Nerve Tissue
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Alkylating Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009