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

Brenda Weigel, Suman Malempati, Joel M. Reid, Stephan D. Voss, Steven Y. Cho, Helen X. Chen, Mark Krailo, Doojduen Villaluna, Peter C. Adamson, Susan M. Blaney

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79 Scopus citations

Abstract

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 9mg/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.

Original languageEnglish (US)
Pages (from-to)452-456
Number of pages5
JournalPediatric Blood and Cancer
Volume61
Issue number3
DOIs
StatePublished - Mar 1 2014

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Keywords

  • Insulin-like growth factor-I receptor
  • Investigational agents
  • Monoclonal antibody
  • Pediatric cancer

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Weigel, B., Malempati, S., Reid, J. M., Voss, S. D., Cho, S. Y., Chen, H. X., Krailo, M., Villaluna, D., Adamson, P. C., & Blaney, S. M. (2014). Phase 2 trial of cixutumumab in children, adolescents, and young adults with refractory solid tumors: A report from the Children's Oncology Group. Pediatric Blood and Cancer, 61(3), 452-456. https://doi.org/10.1002/pbc.24605