OBJECTIVES:

• Determine the acute and dose-limiting toxic effects of cilengitide (EMD 121974) in children with refractory primary brain tumors.
• Determine the maximum tolerated dose of this drug in these patients.
• Determine the inter- and intra-patient variability in the pharmacokinetics of this drug and estimate its renal clearance in these patients.
• Correlate the changes in circulating endothelial cells and circulating endothelial precursors with plasma, serum, and urine angiogeneic protein levels and with clinical outcome in patients treated with this drug.
• Determine, preliminarily, the efficacy and biologic activity of this drug in these patients.

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

Patients receive cilengitide (EMD 121974) IV over 1 hour twice weekly. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of cilengitide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients are expected to experience dose-limiting toxicity. Once the MTD is determined, 6 additional patients are accrued and treated at that dose level.

Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study within 1-1.5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary central nervous system (CNS) tumor, including histologically benign CNS tumors (e.g., low-grade gliomas)*

  • Recurrent or progressive disease
  • Refractory to standard therapy NOTE: *In the absence of histological diagnosis, clinical and radiographic evidence of a brain stem or optic pathway glioma is required
• Patients with bone marrow involvement may be eligible

PATIENT CHARACTERISTICS:

Age

• 21 and under

Performance status

• Karnofsky 50-100% OR
• Lansky 50-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 100,000/mm^3 (transfusion independent)
• Hemoglobin greater than 8.0 g/dL (transfusion allowed)

Hepatic

• Bilirubin normal
• ALT and AST less than 2.5 times upper limit of normal
• No overt hepatic disease

Renal

• Creatinine less than 1.5 times normal OR
• Glomerular filtration rate greater than 70 mL/min
• No overt renal disease

Cardiovascular

• No overt cardiac disease

Pulmonary

• No overt pulmonary disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Neurological deficits allowed provided that they are stable for at least 1 week before study entry
• No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 1 week since prior growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
• More than 6 months since prior bone marrow transplantation
• More than 2 weeks since prior biological agents

Chemotherapy

• At least 6 weeks since prior nitrosoureas

Endocrine therapy

• Concurrent corticosteroids allowed provided that they are at a stable dose for at least 1 week before study entry

Radiotherapy

• At least 6 weeks since prior radiotherapy
• More than 2 weeks since prior local palliative radiotherapy
• More than 3 months since prior craniospinal (more than 24 Gy) or total body radiotherapy

Surgery

• Not specified

Other

• Recovered from prior therapy
• More than 2 weeks since prior investigational agents
• At least 4 weeks since prior myelosuppressive therapy
• Concurrent anticonvulsants allowed
• No other concurrent anticancer agents or therapies
• No other concurrent experimental agents or therapies