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.
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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
COG Phase I Consortium
Arcadia, California, United States
Adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0
Toxicity tables will be constructed to summarize the observed incidence by severity and type of toxicity.
Time frame: Weekly during each course
MTD or recommended phase II dose
MTD will be the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT). DLT is defined as any hematological and non-hematological toxicities that is possible, probably, or definitely attributed to IMC-A12.
Time frame: During course 1
Pharmacokinetics of IMC-A12
Time frame: At baseline, days 1, 8, 15, 22, and 28 of course 1, and days 15 and 28 of course 2
Response rate (complete or partial response) in patients with Ewing sarcoma/peripheral PNET
Confidence intervals will be constructed according to the method of Chang and O'Brien to account for the two-stage design.
Time frame: Up to 30 days after completion of treatment
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