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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Clinical Trials, Phase I
Brain Neoplasms
Pediatrics
Hemorrhage
Maximum Tolerated Dose
Integrin beta3
Cilengitide
Clinical Pharmacology
Incidence
Glioblastoma
Urine

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Phase I clinical trial of cilengitide in children with refractory brain tumors : Pediatric brain tumor consortium study PBTC-012. / MacDonald, Tobey J.; Stewart, Clinton F.; Kocak, Mehmet; Goldman, Stewart; Ellenbogen, Richard G.; Phillips, Peter; Lafond, Deborah; Poussaint, Tina Young; Kieran, Mark W.; Boyett, James M.; Kun, Larry E.

In: Journal of Clinical Oncology, Vol. 26, No. 6, 20.02.2008, p. 919-924.

Research output: Contribution to journalArticle

MacDonald, TJ, Stewart, CF, Kocak, M, Goldman, S, Ellenbogen, RG, Phillips, P, Lafond, D, Poussaint, TY, Kieran, MW, Boyett, JM & Kun, LE 2008, 'Phase I clinical trial of cilengitide in children with refractory brain tumors: Pediatric brain tumor consortium study PBTC-012', Journal of Clinical Oncology, vol. 26, no. 6, pp. 919-924. https://doi.org/10.1200/JCO.2007.14.1812
MacDonald, Tobey J. ; Stewart, Clinton F. ; Kocak, Mehmet ; Goldman, Stewart ; Ellenbogen, Richard G. ; Phillips, Peter ; Lafond, Deborah ; Poussaint, Tina Young ; Kieran, Mark W. ; Boyett, James M. ; Kun, Larry E. / Phase I clinical trial of cilengitide in children with refractory brain tumors : Pediatric brain tumor consortium study PBTC-012. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 6. pp. 919-924.
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T1 - Phase I clinical trial of cilengitide in children with refractory brain tumors

T2 - Pediatric brain tumor consortium study PBTC-012

AU - MacDonald, Tobey J.

AU - Stewart, Clinton F.

AU - Kocak, Mehmet

AU - Goldman, Stewart

AU - Ellenbogen, Richard G.

AU - Phillips, Peter

AU - Lafond, Deborah

AU - Poussaint, Tina Young

AU - Kieran, Mark W.

AU - Boyett, James M.

AU - Kun, Larry E.

PY - 2008/2/20

Y1 - 2008/2/20

N2 - 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.

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