title: Phase 2 trial of cixutumumab in children, adolescents, and young adults with refractory solid tumors: a report from the Children's Oncology Group.
abstract: OBJECTIVE
  This phase 2 study was designed to assess the efficacy of single agent cixutumumab (IMC-A12) and gain further information about associated toxicities and pharmacodynamics in children, adolescents, and young adults with recurrent or refractory solid tumors.
  
  
  METHODS
  Patients with relapsed or refractory solid tumors were treated with 9 mg/kg of cixutumumab as a 1-hour IV infusion once weekly. Strata included: osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, neuroblastoma (evaluable disease), neuroblastoma (measurable disease), Wilms tumor, adrenocortical carcinoma, synovial sarcoma, hepatoblastoma, and retinoblastoma. Correlative studies in consenting patients included an assessment of c-peptide, IGFBP-3, IGF-1, IGF-2, hGH, and insulin in consenting patients.
  
  
  RESULTS
  One hundred sixteen patients with 114 eligible having a median age of 12 years (range, 2-30) were enrolled. Five patients achieved a partial response: 4/20 with neuroblastoma (evaluable only) and 1/20 with rhabdomyosarcoma. Fourteen patients had stable disease for a median of 10 cycles. Hematologic and non-hematologic toxicities were generally mild and infrequent. Serum IGF-1 and IGFBP-3 increased in response to therapy with cixutumumab.
  
  
  CONCLUSIONS
  Cixutumumab is well tolerated in children with refractory solid tumors. Limited objective single-agent activity of cixutumumab was observed; however, prolonged stable disease was observed in 15% of patients. Ongoing studies are evaluating the toxicity and benefit of cixutumumab in combination with other agents that inhibit the IGF pathway.
authors: University of Minnesota, Minneapolis, Minnesota.
authors: Brenda
authors: B
authors: Weigel
authors: Suman
authors: S
authors: Malempati
authors: Joel M
authors: JM
authors: Reid
authors: Stephan D
authors: SD
authors: Voss
authors: Steven Y
authors: SY
authors: Cho
authors: Helen X
authors: HX
authors: Chen
authors: Mark
authors: M
authors: Krailo
authors: Doojduen
authors: D
authors: Villaluna
authors: Peter C
authors: PC
authors: Adamson
authors: Susan M
authors: SM
authors: Blaney
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D012008:Recurrence; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C557414:cixutumumab; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: insulin-like growth factor-I receptor; investigational agents; monoclonal antibody; pediatric cancer
references: J Cell Biochem. 2004 May 1;92(1):77-91
references: 15095405
references: Clin Cancer Res. 2007 Sep 15;13(18 Pt 2):5549s-5555s
references: 17875788
references: Stat Med. 2004 Mar 30;23(6):881-96
references: 15027078
references: Cancer Res. 2005 May 1;65(9):3868-76
references: 15867386
references: Cancer Immunol Immunother. 2007 Mar;56(3):343-57
references: 16832681
references: Cancer Lett. 2003 Jun 10;195(2):127-37
references: 12767520
references: J Clin Oncol. 2012 Jan 20;30(3):256-62
references: 22184397
references: Lancet Oncol. 2010 Feb;11(2):129-35
references: 20036194
references: Am J Pathol. 1989 Dec;135(6):961-6
references: 2556929
references: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references: 10655437
references: J Clin Invest. 1989 Sep;84(3):829-39
references: 2547840
references: Endocr Rev. 1995 Apr;16(2):143-63
references: 7540132
references: Cell Growth Differ. 1990 Jul;1(7):325-31
references: 2177632
references: Nat Rev Cancer. 2008 Dec;8(12):915-28
references: 19029956
references: Cancer Res. 2006 Feb 15;66(4):2391-402
references: 16489046
references: J Biol Chem. 1997 Dec 5;272(49):30822-7
references: 9388225
references: Clin Cancer Res. 2001 Jun;7(6):1790-7
references: 11410521
references: Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5828-32
references: 8390684
references: Mol Cancer Ther. 2008 Sep;7(9):2599-608
references: 18790743
references: Clin Cancer Res. 2006 Aug 1;12(15):4755-65
references: 16899627
references: Pediatr Blood Cancer. 2012 May;58(5):729-35
references: 21630428
references: Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6153-60
references: 17062692
references: Pediatr Blood Cancer. 2010 Jul 1;54(7):921-6
references: 20166202
references: J Clin Oncol. 2011 Dec 1;29(34):4541-7
references: 22025149
references: Cancer Res. 2003 Aug 15;63(16):5073-83
references: 12941837
references: Mol Cancer Ther. 2011 Dec;10(12):2437-48
references: 21980128
references: Eur J Cancer. 1995;31A(2):256-61
references: 7718334
references: Cancer Res. 2007 Feb 1;67(3):1155-62
references: 17283150
references: Cancer Res. 2003 Dec 15;63(24):8912-21
references: 14695208
references: Clin Cancer Res. 2006 Nov 15;12(22):6772-80
references: 17121898
references: Growth Horm IGF Res. 2001 Oct;11(5):289-97
references: 11735247