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

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ClinicalTrials.gov Identifier: NCT00471653
Recruitment Status : Terminated (low accrual)
First Posted : May 10, 2007
Last Update Posted : July 9, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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
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 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 : November 11, 2006
Actual Primary Completion Date : November 12, 2008
Actual Study Completion Date : August 18, 2009





Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
High grade glioma
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

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 ClinicalTrials.gov identifier (NCT number): NCT00471653


Locations
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)
Investigators
Study Chair: Stuart A. Grossman, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00471653     History of Changes
Other Study ID Numbers: J0684
P30CA006973 ( U.S. NIH Grant/Contract )
CDR0000543866
NA_00004964 ( Other Identifier: JHM IRB )
First Posted: May 10, 2007    Key Record Dates
Last Update Posted: July 9, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
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

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