Phase I Study of Cilengitide (EMD 121974) in Children With Refractory Brain Tumors
I. To describe the acute and dose-limiting toxicities (DLT) and define the maximum tolerated
dose (MTD) of cilengitide (EMD 121974) when administered to children and adolescents with
refractory primary brain tumors.
I. To obtain preliminary evidence of biologic activity by determining alterations in tissue
perfusion, tumor blood flow and metabolic activity using MR perfusion, PET and MRS and
correlating these findings with changes in tumor size by volumetric MRI.
II. To characterize inter- and intra-patient variability in the pharmacokinetics of
cilengitide and to estimate cilengitide renal clearance in this patient population.
III. To characterize the pharmacogenetic polymorphisms in drug transporters (e.g., MRP4,
BCRP) and relate to cilengitide disposition.
IV. To evaluate changes in circulating endothelial cells (CECs) and circulating endothelial
precursors (CEPs) in patients treated with cilengitide, and to investigate the correlation
between changes in CECs and CEPs, plasma, serum and urine angiogenic protein levels such as
VEGF, and clinical outcome.
V. To obtain preliminary information about the efficacy of cilengitide in this patient
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of cilengitide
Pediatric Brain Tumor Consortium
United States: Food and Drug Administration
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