Phase 2 trial of cixutumumab in children, adolescents, and young adults with refractory solid tumors: a report from the Children's Oncology Group

Pediatr Blood Cancer. 2014 Mar;61(3):452-6. doi: 10.1002/pbc.24605. Epub 2013 Aug 17.


Purpose: 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.

Patients and 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.

Conclusion: 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.

Keywords: insulin-like growth factor-I receptor; investigational agents; monoclonal antibody; pediatric cancer.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Insulin-Like Growth Factor I / analysis
  • Male
  • Neoplasms / drug therapy*
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Recurrence
  • Young Adult


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • cixutumumab
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1