- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00471653
Pharmacokinetics in Patients With Newly Diagnosed High-Grade Glioma Receiving Temozolomide and Radiation Therapy
A Pharmacokinetic and Pharmacogenomic Study of Patients With High-Grade Gliomas Receiving Daily Radiation Therapy and Temozolomide
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.
Study Overview
Status
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 Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
California
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Duarte, California, United States, 91010-3000
- City of Hope Comprehensive Cancer Center
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Maryland
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Baltimore, Maryland, United States, 21231-2410
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetics (PK) of temozolomide (TMZ) in patients with severe thrombocytopenia after standard first-line therapy as measured by Area Under the Curve (AUC)
Time Frame: 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.
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Day 1, Day 22, Day 43
|
Pharmacokinetics (PK) of temozolomide (TMZ) in patients with severe thrombocytopenia after standard first-line therapy as measured by maximum drug concentration (Cmax)
Time Frame: 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.
|
Day 1, Day 22, Day 43
|
Pharmacokinetic (PK) profile of temozolomide (TMZ) in patients without severe thrombocytopenia after standard first-line therapy as measured by AUC
Time Frame: 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.
|
Day 1, Day 22, Day 43
|
Pharmacokinetic (PK) profile of temozolomide (TMZ) in patients without severe thrombocytopenia after standard first-line therapy as measured by Cmax
Time Frame: 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.
|
Day 1, Day 22, Day 43
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Presence of single nucleotide polymorphisms in the O6-methylguanine-DNA methyltransferase gene.
Time Frame: 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.
|
Day 1
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Nervous System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Hematologic Diseases
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Blood Platelet Disorders
- Glioma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Thrombocytopenia
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Temozolomide
Other Study ID Numbers
- J0684
- P30CA006973 (U.S. NIH Grant/Contract)
- CDR0000543866
- NA_00004964 (Other Identifier: JHM IRB)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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