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

Condition(s) targeted: Brain and Central Nervous System Tumors; Cancer-Related Problem/Condition

Intervention: temozolomide (Drug); comparative genomic hybridization (Procedure); laboratory biomarker analysis (Procedure); pharmacological study (Procedure); polymorphism analysis (Procedure); radiation therapy (Procedure)

Phase: N/A

Status: Recruiting

Sponsored by: Sidney Kimmel Comprehensive Cancer Center

Official(s) and/or principal investigator(s):
Stuart A. Grossman, MD, Study Chair, Affiliation: Sidney Kimmel Comprehensive Cancer Center

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.

Official title: A Pharmacokinetic and Pharmacogenomic Study of Patients With High-Grade Gliomas Receiving Daily Radiation Therapy and Temozolomide

Study design: Treatment

Primary outcome: Correlation of pharmacokinetics with incidence of dose-limiting toxicities

Secondary outcome:

Maximum concentration of temozolomide

Polymorphisms in the MGMT repair gene

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

City of Hope Comprehensive Cancer Center, Duarte, California 91010-3000, United States; Recruiting
Clinical Trials Office - City of Hope Comprehensive Cancer Cen, Phone: 800-826-4673, Email: becomingapatient@coh.org

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States; Recruiting
Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce, Phone: 410-955-8804, Email: jhcccro@jhmi.edu

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: November 2006
Last updated: October 18, 2008