title: Phase I clinical trial of cilengitide in children with refractory brain tumors: Pediatric Brain Tumor Consortium Study PBTC-012.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Children's National Medical Center, 111 Michigan Ave, NW, Washington, DC 20010, USA. tmacdona@cnmc.org
authors.forename: Tobey J
authors.initials: TJ
authors.lastname: MacDonald
authors.forename: Clinton F
authors.initials: CF
authors.lastname: Stewart
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kocak
authors.forename: Stewart
authors.initials: S
authors.lastname: Goldman
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ellenbogen
authors.forename: Peter
authors.initials: P
authors.lastname: Phillips
authors.forename: Deborah
authors.initials: D
authors.lastname: Lafond
authors.forename: Tina Young
authors.initials: TY
authors.lastname: Poussaint
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kieran
authors.forename: James M
authors.initials: JM
authors.lastname: Boyett
authors.forename: Larry E
authors.initials: LE
authors.lastname: Kun
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000293:Adolescent; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D012910:Snake Venoms / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D020533:Angiogenesis Inhibitors; D012910:Snake Venoms; C422910:Cilengitide