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

PURPOSE: Phase I trial to study the effectiveness of cilengitide in treating children who have recurrent, progressive, or refractory primary CNS tumors.

Condition	Treatment or Intervention	Phase
childhood brain tumor childhood meningioma childhood spinal cord tumors	Drug: cilengitide  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: growth factor antagonist therapy	Phase I

Further Study Details: 

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.

Ages Eligible for Study:  up to  21 Years,  Genders Eligible for Study:  Both

Criteria

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 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

California
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94143,  United States; Recruiting
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States; Recruiting
Illinois
      Children's Memorial Hospital - Chicago, Chicago,  Illinois,  60614,  United States; Recruiting
Maryland
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104-4318,  United States; Recruiting
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
Tennessee
      St. Jude Children's Research Hospital, Memphis,  Tennessee,  38105-2794,  United States; Recruiting
Texas
      Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital, Houston,  Texas,  77030-2399,  United States; Recruiting
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States; Recruiting

Study chairs or principal investigators

Tobey MacDonald, MD,  Study Chair,  Children's National Medical Center   

Study ID Numbers:  CDR0000305859; PBTC-012; NCT00063973
Record last reviewed:  July 2003
Last Updated:  April 4, 2005
Record first received:  July 8, 2003
ClinicalTrials.gov Identifier:  NCT00063973
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08