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

AbstractPURPOSE:
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.
AuthorsTobey 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
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 26 Issue 6 Pg. 919-24 (Feb 20 2008) ISSN: 1527-7755 [Electronic] United States
PMID18281665 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Angiogenesis Inhibitors
  • Snake Venoms
  • Cilengitide
Topics
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
  • Adolescent
  • Adult
  • Angiogenesis Inhibitors (administration & dosage, adverse effects, pharmacokinetics)
  • Brain Neoplasms (drug therapy, pathology)
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Female
  • Genotype
  • Humans
  • Infant
  • Infusions, Intravenous
  • Magnetic Resonance Imaging
  • Male
  • Snake Venoms (administration & dosage, adverse effects, pharmacokinetics)
  • Treatment Outcome

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