Brain Tumor, Central Nervous System Tumor
Conditions
Keywords
childhood high-grade cerebral astrocytoma
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of temozolomide plus lomustine followed by radiation therapy in treating patients who have high-grade malignant glioma.
Detailed description
OBJECTIVES: * Determine the maximum tolerated dose of temozolomide when administered with lomustine in patients with high-grade malignant gliomas. * Determine the dose-limiting toxic effects of this regimen in these patients. * Evaluate the feasibility of radiotherapy after this treatment regimen in this patient population. * Evaluate the radiographic responses in patients treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of temozolomide. Patients receive oral temozolomide on days 1-5 and oral lomustine on day 1. Treatment continues every 28 days, if blood counts have recovered, for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo radiotherapy on days 1-5 weekly for 6 weeks. Patients continue the same chemotherapy regimen for up to 6 more courses beginning 4 weeks after completion of radiotherapy. Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed for survival. PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.
Interventions
DRUGlomustine
DRUGtemozolomide
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed high-grade malignant glioma of one of the following subtypes: * Glioblastoma * Anaplastic astrocytoma * Anaplastic oligoastrocytoma * Gliomatosis cerebri * No disseminated disease or primary spinal cord malignancies * Measurable intracranial residual disease by MRI PATIENT CHARACTERISTICS: Age: * 3 and over * Under 22 at time of diagnosis Performance status: * Karnofsky 50-100% if over 10 years of age * Lansky 50-100% if 10 years of age or under Life expectancy: * At least 8 weeks Hematopoietic: * Absolute neutrophil count at least 1,000/mm\^3 * Platelet count at least 100,000/mm\^3 (transfusion independent) * Hemoglobin at least 8.0 g/dL (RBC transfusions allowed) Hepatic: * Bilirubin no greater than 1.5 times normal for age * SGPT no greater than 2.5 times normal for age * Albumin at least 2 g/dL Renal: * Creatinine no greater than 1.5 times normal for age OR * Creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal for age Pulmonary: * No dyspnea at rest * No exercise intolerance * Pulse oximetry at least 94% Other: * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No uncontrolled infection PRIOR CONCURRENT THERAPY: Biologic therapy: * No prior biologic therapy * No concurrent prophylactic hematopoietic growth factors Chemotherapy: * No prior chemotherapy Endocrine therapy: * Prior corticosteroid therapy allowed * No concurrent corticosteroids as antiemetic Radiotherapy: * No prior radiotherapy Surgery: * No more than 31 days since prior maximal neurosurgical procedure Other: * No concurrent phenobarbital or cimetidine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Length of study | This trial is a phase I evaluation of temozolomide in combination with a fixed dose of CCNU with the starting dose for temozolomide |
Countries
Australia, Canada, Netherlands, New Zealand, Puerto Rico, Switzerland, United States
Outcome results
None listed