Clinical Trial Finder

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

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.