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

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Terminated

CT.gov ID

NCT00471653

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

33.2

Actual Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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

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.

Study Design

Study Type:

Observational

Actual Enrollment :

10 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Nov 11, 2006

Actual Primary Completion Date :

Nov 12, 2008

Actual Study Completion Date :

Aug 18, 2009

Outcome Measures

Primary Outcome Measures

Pharmacokinetics (PK) of temozolomide (TMZ) in patients with severe thrombocytopenia after standard first-line therapy as measured by Area Under the Curve (AUC) [Day 1, Day 22, Day 43]
AUC (mg*h/L)in patients who develop severe thrombocytopenia after receiving standard first-line therapy of temozolomide (TMZ) for management of newly diagnosed high-grade gliomas.
Pharmacokinetics (PK) of temozolomide (TMZ) in patients with severe thrombocytopenia after standard first-line therapy as measured by maximum drug concentration (Cmax) [Day 1, Day 22, Day 43]
Cmax in patients who develop severe thrombocytopenia after receiving standard first-line therapy of temozolomide (TMZ) for management of newly diagnosed high-grade gliomas.
Pharmacokinetic (PK) profile of temozolomide (TMZ) in patients without severe thrombocytopenia after standard first-line therapy as measured by AUC [Day 1, Day 22, Day 43]
AUC in patients in patients who do not develop severe thrombocytopenia after receiving standard first-line therapy of TMZ for management of newly diagnosed high-grade gliomas.
Pharmacokinetic (PK) profile of temozolomide (TMZ) in patients without severe thrombocytopenia after standard first-line therapy as measured by Cmax [Day 1, Day 22, Day 43]
Cmax in patients in patients who do not develop severe thrombocytopenia after receiving standard first-line therapy of TMZ for management of newly diagnosed high-grade gliomas.

Secondary Outcome Measures

Presence of single nucleotide polymorphisms in the O6-methylguanine-DNA methyltransferase gene. [Day 1]
Presence of single nucleotide polymorphisms in the O6-methylguanine-DNA methyltransferase gene of patients who develop thrombocytopenia after receiving standard first-line therapy for management of newly diagnosed high-grade gliomas.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
2	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410