RATIONALE: EMD 121974 may stop the growth of cancer by stopping blood flow to the tumor.

PURPOSE: Phase I/II trial to study the effectiveness of EMD 121974 in treating patients who have progressive or recurrent malignant glioma.

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of EMD 121974 in patients with progressive or recurrent malignant glioma.
• Determine the 6-month progression-free survival, clinical response rate, duration of progression-free survival, and overall survival in patients treated with this drug.
• Determine the effects of this drug on tumor perfusion, measured with magnetic resonance perfusion scan, and markers for angiogenesis in these patients.

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

Patients receive EMD 121974 IV over 1 hour twice weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 6-12 patients receive escalating doses of EMD 121974 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which more than 2 of 6 or 4 of 12 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at the MTD.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A minimum of 6 patients will be accrued for phase I of this study within 2-3 months. A total of 23-38 patients will be accrued for phase II of this study within 5-10 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant glioma that is progressive or recurrent after radiotherapy and/or chemotherapy

  • Eligible subtypes:

    • Anaplastic astrocytoma
    • Anaplastic oligodendroglioma
    • Glioblastoma multiforme
  • Prior low-grade glioma that has progressed to a high-grade glioma (by biopsy) after radiotherapy and/or chemotherapy allowed
• Measurable disease by volumetric and magnetic resonance perfusion scan
• Prior biopsy or resection of recurrent brain tumor allowed

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 normal
• Transaminases no greater than 2.5 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No advanced coronary artery disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No serious concurrent infection or medical illness that would preclude study
• No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer
• No history of wound healing disorders
• No peptic ulcer disease within the past year
• Mini mental score of at least 15
• Willing and able to undergo MRI

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent filgrastim (G-CSF)

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
• No more than 2 prior chemotherapy regimens

Endocrine therapy:

• Prior corticosteroids allowed if on stable dose for at least 5 days prior to study
• Concurrent corticosteroids (e.g., dexamethasone) allowed as clinically needed

Radiotherapy:

• See Disease Characteristics
• At least 3 months since prior radiotherapy and recovered

Surgery:

• See Disease Characteristics
• At least 1 week since prior surgery and recovered
• No concurrent elective surgery or dental extractions

Other:

• No other concurrent investigational agents