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Phase 2 trial of cixutumumab in children, adolescents, and young adults with refractory solid tumors: A report from the Children's Oncology Group
Author(s) -
Weigel Brenda,
Malempati Suman,
Reid Joel M.,
Voss Stephan D.,
Cho Steven Y.,
Chen Helen X.,
Krailo Mark,
Villaluna Doojduen,
Adamson Peter C.,
Blaney Susan M.
Publication year - 2014
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24605
Subject(s) - medicine , family medicine , library science , pediatrics , gerontology , computer science
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. Pediatr Blood Cancer 2014;61:452–456. © 2013 Wiley Periodicals, Inc.