IMC-A12 in Treating Young Patients With Relapsed or Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor or Other Solid Tumor

Unspecified Childhood Solid Tumor, Protocol Specific Clinical Trial

Official title: A Phase I Study of IMC-A12 (Anti-IGF-I Receptor Monoclonal Antibody, NSC #742460) in Children With Relapsed/Refractory Solid Tumors

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms
• Neuroectodermal Tumors
• Neuroectodermal Tumors, Primitive
• Neuroectodermal Tumors, Primitive, Peripheral
• Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
• Sarcoma
• Sarcoma, Ewing
• Unspecified Childhood Solid Tumor, Protocol Specific

• NCT number: NCT00609141
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 1
• Start date: January 2008