Phase I clinical trial of cilengitide in children with refractory brain tumors: Pediatric Brain Tumor Consortium Study PBTC-012

J Clin Oncol. 2008 Feb 20;26(6):919-24. doi: 10.1200/JCO.2007.14.1812.


Purpose: A phase I trial of the antiangiogenesis agent cilengitide (EMD 121974), an alpha v beta 3,5 integrin antagonist, was performed to estimate the maximum-tolerated dose (MTD) and describe dose-limiting toxicities (DLTs) and the incidence and severity of other toxicities when administered to children with refractory brain tumors.

Patients and methods: Thirty-one assessable patients received intravenous cilengitide over 1 hour twice a week for up to 52 weeks at dosages from 120 to 2,400 mg/m(2). Serial blood and urine samples for clinical pharmacology studies were obtained in a subset of consenting patients.

Results: No DLTs were observed, and thus, the MTD was not estimated. Three of 13 patients at the dosage level of 2,400 mg/m(2) experienced grade 3 or 4 intratumoral hemorrhage (ITH) possibly related to the study drug; however, two of the ITH events were asymptomatic and, by the current toxicity criteria, would be classified as grade 1. For patients treated at cilengitide 2,400 mg/m(2), the 6-month cumulative incidence estimate of ITH is 23% (SE = 13%). No ITH was observed at 1,800 mg/m(2). Three patients completed 1 year of protocol therapy; one patient with glioblastoma multiforme demonstrated complete response, and two patients had stable disease (SD). An additional patient had SD for more than 5 months.

Conclusion: The phase II dosage of intravenous cilengitide in children with refractory brain tumors is 1,800 mg/m(2). A phase II trial to assess the efficacy of cilengitide therapy for children with refractory brain tumors is being developed by the Children's Oncology Group.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Adolescent
  • Adult
  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / adverse effects*
  • Angiogenesis Inhibitors / pharmacokinetics
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Female
  • Genotype
  • Humans
  • Infant
  • Infusions, Intravenous
  • Magnetic Resonance Imaging
  • Male
  • Snake Venoms / administration & dosage*
  • Snake Venoms / adverse effects*
  • Snake Venoms / pharmacokinetics
  • Treatment Outcome


  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Angiogenesis Inhibitors
  • Snake Venoms
  • Cilengitide