IMC-A12 in Treating Young Patients With Relapsed or Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor or Other Solid Tumor
Condition: Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Unspecified Childhood Solid Tumor, Protocol Specific
MeSH terms: Neoplasms; Sarcoma; Sarcoma, Ewing; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase I clinical trial is studying the side effects and best dose of IMC-A12 in treating
      young patients with relapsed or refractory Ewing sarcoma/peripheral primitive neuroectodermal
      tumor or other solid tumors. Monoclonal antibodies, such as IMC-A12, can block cancer growth
      in different ways. Some block the ability of cancer cells to grow and spread. Others find
      cancer cells and help kill them or carry cancer-killing substances to them.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To estimate the maximum tolerated dose (MTD) or recommended phase II dose of IMC-A12
      (cixutumumab) in children with relapsed or refractory solid tumors using a limited
      dose-escalation strategy.

      II. To define and describe the toxicities of this drug in children with relapsed or
      refractory solid tumors.

      III. To characterize the pharmacokinetics of this drug in children with relapsed or
      refractory solid tumors.

      SECONDARY OBJECTIVES:

      I. To preliminarily define the antitumor activity of this drug in children with relapsed or
      refractory solid tumors within the confines of a phase I study.

      II. To obtain initial phase II efficacy data on the antitumor activity of this drug in
      children with Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET).

      III. To examine change in IGF-IR and insulin receptor (IR) levels and IGF-IR and IR
      activation in lymphocytes as biomarkers of IMC-A12 action and specificity.

      IV. To evaluate the effect of this drug on circulating levels of proteins involved in linear
      growth and glucose homeostasis, including IGF-I, IGF-II, IGF-BP3, growth hormone, insulin,
      and C-peptide.

      V. To develop exploratory data concerning biomarkers of activity.

      OUTLINE: This is a dose-escalation study.

      Patients receive cixutumumab IV over 1 hour on days 1, 8, 15, and 22. Treatment repeats every
      4 weeks for up to 2 years in the absence of unacceptable toxicity or disease progression.

      Patients undergo blood sample collection periodically for pharmacokinetic, immunogenicity,
      and other correlative studies. Samples are analyzed for serum levels of IGF-I, IGF-II,
      IGF-BP3, growth hormone, insulin, and C-peptide; trough concentrations and PK sampling; and
      biomarkers, including IGF-IR expression and phosphorylation and insulin receptor expression
      and phosphorylation via immunoprecipitation and Western immunoblotting. Tumor tissue samples
      from patients with Ewing sarcoma/peripheral PNET are banked for future research.

      After completion of study treatment, patients are followed at 30 days.
    

Intervention name(s): cixutumumab; pharmacological study; laboratory biomarker analysis
Intervention type(s): Biological; Other; Other
Intervention description(s): Given IV; Correlative studies; Correlative studies
Other intervention name(s): anti-IGF-1R recombinant monoclonal antibody IMC-A12; IMC-A12; pharmacological studies
Intervention MeSH terms: Antibodies, Monoclonal
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment