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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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 2014

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Young Adult
Neoplasms
Neuroblastoma
Insulin-Like Growth Factor Binding Protein 3
Rhabdomyosarcoma
Insulin-Like Growth Factor I
Adrenocortical Carcinoma
Hepatoblastoma
Synovial Sarcoma
Ewing's Sarcoma
Insulin-Like Growth Factor II
Wilms Tumor
Retinoblastoma
anti-IGF-1R antibody A12
Osteosarcoma
Insulin
Peptides
Serum

Keywords

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

ASJC Scopus subject areas

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

Cite this

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

In: Pediatric Blood and Cancer, Vol. 61, No. 3, 03.2014, p. 452-456.

Research output: Contribution to journalArticle

Weigel, B, Malempati, S, Reid, JM, Voss, SD, Cho, SY, Chen, HX, Krailo, M, Villaluna, D, Adamson, PC & Blaney, SM 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, vol. 61, no. 3, pp. 452-456. https://doi.org/10.1002/pbc.24605
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. / Phase 2 trial of cixutumumab in children, adolescents, and young adults with refractory solid tumors : A report from the Children's Oncology Group. In: Pediatric Blood and Cancer. 2014 ; Vol. 61, No. 3. pp. 452-456.
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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.",
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T2 - A report from the Children's Oncology Group

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AU - Malempati, Suman

AU - Reid, Joel M

AU - Voss, Stephan D.

AU - Cho, Steven Y.

AU - Chen, Helen X.

AU - Krailo, Mark

AU - Villaluna, Doojduen

AU - Adamson, Peter C.

AU - Blaney, Susan M.

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N2 - 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.

AB - 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.

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