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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date May 8, 2007
First Posted Date May 10, 2007
Last Update Posted Date July 9, 2018
Actual Study Start Date November 11, 2006
Actual Primary Completion Date November 12, 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 5, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures
 (submitted: May 8, 2007)
Correlation of pharmacokinetics with incidence of dose-limiting toxicities
Change History
Current Secondary Outcome Measures
 (submitted: July 5, 2018)
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.
Original Secondary Outcome Measures
 (submitted: May 8, 2007)
  • Maximum concentration of temozolomide
  • Polymorphisms in the MGMT repair gene
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title 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
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.

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
Study Design Observational Model: Other
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Probability Sample
Study Population High grade glioma
Condition
  • Brain and Central Nervous System Tumors
  • Thrombocytopenia
Intervention
  • Drug: temozolomide
  • Genetic: comparative genomic hybridization
  • Genetic: polymorphism analysis
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
  • Radiation: radiation therapy
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Terminated
Actual Enrollment
 (submitted: July 5, 2018)
10
Original Enrollment
 (submitted: May 8, 2007)
150
Actual Study Completion Date August 18, 2009
Actual Primary Completion Date November 12, 2008   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT00471653
Other Study ID Numbers J0684
P30CA006973 ( U.S. NIH Grant/Contract )
CDR0000543866
NA_00004964 ( Other Identifier: JHM IRB )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators National Cancer Institute (NCI)
Investigators
Study Chair: Stuart A. Grossman, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date July 2018