• Acute and dose-limiting toxicities [ Designated as safety issue: Yes ]
• Maximum tolerated dose [ Time Frame: First four weeks of therapy ] [ Designated as safety issue: Yes ]

• Correlation of imaging parameters (tissue perfusion, tumor blood flow, and metabolic activity as measured by MR perfusion, PET, and MRS) with tumor size as measured by volumetric MRI [ Designated as safety issue: No ]
• Pharmacokinetics [ Designated as safety issue: No ]
• Correlation of circulating endothelial cells and circulating endothelial precursors with angiogenic protein levels and outcome [ Designated as safety issue: No ]
• Efficacy [ Designated as safety issue: No ]

RATIONALE: Cilengitide may slow the growth of brain cancer cells by stopping blood flow to the tumor.

PURPOSE: This phase I trial is studying the side effects and best dose of cilengitide in treating children with recurrent, progressive, or refractory primary CNS tumors.

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.
• Correlate tissue perfusion, tumor blood flow and metabolic activity using MR perfusion, PET and MRS with changes in tumor size by volumetric MRI
• 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 angiogenic protein levels and with clinical outcome in patients treated with this drug.
• Determine, preliminarily, the efficacy 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 for a total of 12 patients at the MTD.

Patients receiving treatment are followed weekly for the first three months then monthly for one year or 13 courses of treatment. Patients discontinuing treatment will be followed for resolution of all adverse events occurring while on treatment and/or within 30 days of the last administration of study drug. Patients will be followed for the shortest of 1) three months after the last protocol based treatment, or 2) the date other therapy is initiated.

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