Brain and Central Nervous System Tumors
Conditions
Keywords
adult anaplastic oligodendroglioma, recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult giant cell glioblastoma, adult gliosarcoma
Brief summary
RATIONALE: Drugs used in chemotherapy, such as gimatecan, work in different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: This phase I/II trial is studying the side effects and best dose of gimatecan in treating patients with recurrent or progressive primary malignant glioma.
Detailed description
OBJECTIVES: Primary * Determine the maximum tolerated dose (MTD) of gimatecan in patients with recurrent or progressive primary malignant glioma treated with or without concurrent enzyme-inducing anticonvulsant drugs. * Determine whether this drug has sufficient activity to warrant further development in these patients. (phase II) Secondary * Determine the qualitative and quantitative toxic effects of this drug in these patients. * Determine the pharmacokinetic behaviors of this drug in these patients. * Correlate the principal toxic effects with the pertinent pharmacokinetic parameters of this drug in these patients. * Determine the antitumor activity of this drug in these patients. OUTLINE: This is an open-label, dose-escalation, multicenter study. Patients are stratified according to the concurrent use of enzyme-inducing anticonvulsant drugs (yes vs no). * Phase I: Patients receive oral gimatecan once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gimatecan 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. * Phase II: Patients receive gimatecan as in phase I at the MTD. Patients are followed for at least 1 month and then every 2 months thereafter. PROJECTED ACCRUAL: Approximately 30-83 patients (30-42 for phase I \[15-21 per stratum\] and 21-41 for phase II) will be accrued for this study within 24 months.
Interventions
DRUGgimatecan
Sponsors
National Cancer Institute (NCI)
Jonsson Comprehensive Cancer Center
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, or anaplastic oligodendroglioma) * Recurrent or progressive primary CNS neoplasm by contrast-enhanced MRI * Tumor progression after prior surgery, radiotherapy, or chemotherapy * Measurable or evaluable disease * Failed prior standard curative or palliative therapy (phase I only) PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Karnofsky 60-100% Life expectancy * At least 3 months Hematopoietic * Absolute neutrophil count ≥ 2,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * SGPT and SGOT ≤ 1.5 times upper limit of normal (ULN) (3 times ULN if liver metastases are present) * Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if liver metastases are present) * Bilirubin normal Renal * Creatinine ≤ 1.5 times ULN Cardiovascular * No myocardial infarction with the past year * No heart failure (including cardiac insufficiency controlled by digitalis and diuretics) * No irreversible arrhythmias requiring permanent medication * No uncontrolled hypertension Gastrointestinal * No gastrointestinal dysfunction that would alter absorption or motility, such as any of the following: * Active peptic ulcer * Inflammatory bowel disease * Known intolerance to lactose * Malabsorption syndromes * Intestinal sub-occlusion Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception * No active infection * No mentally incapacitated patients * No other concurrent severe disease that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent immunotherapy Chemotherapy * See Disease Characteristics * At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) * No more than 1 prior chemotherapy regimen * No other concurrent chemotherapy Endocrine therapy * Concurrent corticosteroids allowed if dose stable for the past 2 weeks * No concurrent hormonal therapy Radiotherapy * See Disease Characteristics * At least 4 weeks since prior radiotherapy * No concurrent radiotherapy Surgery * See Disease Characteristics * At least 3 weeks since prior surgical resection * No prior gastrointestinal surgery that would affect drug absorption Other * More than 4 weeks since prior participation in any other investigational drug study * More than 72 hours since prior systemic antibiotics * No concurrent H2 antagonists, antacids, or proton pump inhibitors * If any of these therapies are necessary, ≥ 3 hours must elapse after gimatecan administration * No other concurrent anticancer therapy * No other concurrent investigational drugs * No other concurrent immunosuppressive agents
Countries
United States
Outcome results
None listed