Phase I clinical trial of cilengitide in children with refractory brain tumors: Pediatric brain tumor consortium study PBTC-012

Tobey J. MacDonald, Clinton F. Stewart, Mehmet Kocak, Stewart Goldman, Richard G. Ellenbogen, Peter Phillips, Deborah Lafond, Tina Young Poussaint, Mark W. Kieran, James M. Boyett, Larry E. Kun

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Abstract

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/m2. 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/m2 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/m2, the 6-month cumulative incidence estimate of ITH is 23% (SE = 13%). No ITH was observed at 1,800 mg/m2. 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/m2. 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.

Original languageEnglish (US)
Pages (from-to)919-924
Number of pages6
JournalJournal of Clinical Oncology
Volume26
Issue number6
DOIs
StatePublished - Feb 20 2008

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

MacDonald, T. J., Stewart, C. F., Kocak, M., Goldman, S., Ellenbogen, R. G., Phillips, P., Lafond, D., Poussaint, T. Y., Kieran, M. W., Boyett, J. M., & Kun, L. E. (2008). Phase I clinical trial of cilengitide in children with refractory brain tumors: Pediatric brain tumor consortium study PBTC-012. Journal of Clinical Oncology, 26(6), 919-924. https://doi.org/10.1200/JCO.2007.14.1812