Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Cilengitide in Treating Children With Refractory Primary Brain Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 21 and under NCI PBTC-012 NCT00063973

Objectives

1. Determine the acute and dose-limiting toxic effects of cilengitide (EMD 121974) in children with refractory primary brain tumors.
2. Determine the maximum tolerated dose of this drug in these patients.
3. Determine the inter- and intra-patient variability in the pharmacokinetics of this drug and estimate its renal clearance in these patients.
4. 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.
5. Determine, preliminarily, the efficacy and biologic activity of this drug in these patients.

Entry 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 or optic pathway glioma is required]




• Patients with bone marrow involvement may be eligible

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

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/mm³
• Platelet count greater than 100,000/mm³ (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

Expected Enrollment

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

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.

MacDonald TJ, Stewart CF, Kocak M, et al.: Phase I clinical trial of cilengitide in children with refractory brain tumors: Pediatric Brain Tumor Consortium Study PBTC-012. J Clin Oncol 26 (6): 919-24, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Pediatric Brain Tumor Consortium

Tobey MacDonald, MD, Protocol chair		Ph: 202-884-2146 Email: tmacdona@cnmc.org

Registry Information
Official Title		Phase I Study of Cilengitide (EMD 121974) in Children with Refractory Brain Tumors
Trial Start Date		2003-07-29
Trial Completion Date		2008-03-13
Registered in ClinicalTrials.gov		NCT00063973
Date Submitted to PDQ		2003-05-13
Information Last Verified		2005-05-11
NCI Grant/Contract Number		CA81457

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