Gimatecan in Treating Patients With Recurrent or Progressive Primary Malignant Glioma

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