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

Johns Hopkins Medicine

Status: Terminated

Conditions: Thrombocytopenia; Brain and Central Nervous System Tumors

Treatments: Genetic: polymorphism analysis; Radiation: radiation therapy; Other: pharmacological study; Genetic: comparative genomic hybridization; Drug: temozolomide; Other: laboratory biomarker analysis

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT00471653

CDR0000543866

P30CA006973 (U.S. NIH Grant/Contract)

NA_00004964 (Other Identifier)

J0684

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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