Brain and Central Nervous System Tumors, Thrombocytopenia
Conditions
Keywords
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
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.
Interventions
DRUGtemozolomide
GENETICcomparative genomic hybridization
GENETICpolymorphism analysis
OTHERlaboratory biomarker analysis
OTHERpharmacological study
RADIATIONradiation therapy
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed