RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of atrasentan in treating patients who have progressive or recurrent malignant glioma.

OBJECTIVES:

• Determine the maximum tolerated dose of atrasentan in patients with progressive or recurrent malignant glioma.
• Describe the pharmacokinetics of this drug in these patients.
• Assess preliminary evidence of therapeutic activity of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive oral atrasentan once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 2-10 patients receive escalating doses of atrasentan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 1 patient experiences dose-limiting toxicity.

Patients are followed every 2 months.

PROJECTED ACCRUAL: Approximately 35 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant glioma

  • Anaplastic astrocytoma
  • Anaplastic oligodendroglioma
  • Glioblastoma multiforme

• Progressive or recurrent after prior radiotherapy with or without chemotherapy

  • Prior low-grade glioma that has progressed to high-grade after therapy allowed

• Measurable disease by MRI or CT scan

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• Transaminases no greater than 4 times upper limit of normal
• Hepatitis A, B, and C negative

Renal:

• Creatinine no greater than 1.7 mg/dL

Cardiovascular:

• No New York Heart Association class II, III, or IV cardiac disease

Other:

• HIV negative
• Mini mental score at least 15
• No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer
• No serious concurrent infection
• No other concurrent medical illness that would preclude study entry
• No alcoholism or drug addiction within the past 6 months
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent anticancer immunotherapy

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
• No more than 1 prior chemotherapy regimen
• No prior or concurrent polifeprosan 20 with carmustine implant (Gliadel wafer)
• No prior atrasentan
• No other concurrent anticancer chemotherapy

Endocrine therapy:

• No concurrent anticancer hormonal therapy

Radiotherapy:

• See Disease Characteristics
• At least 3 months since prior radiotherapy and recovered
• No concurrent anticancer radiotherapy

Surgery:

• No concurrent anticancer surgery

Other:

• Recovered from prior therapy
• No more than 1 prior treatment regimen
• No other concurrent investigational agents