A Phase I Study of IMC-A12 (Anti-IGF-I Receptor Monoclonal Antibody, IND #100947, NSC #742460) in Children With Relapsed/Refractory Solid Tumors
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
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.
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,
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
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Weekly during each course
COG Phase I Consortium
United States: Food and Drug Administration
|COG Phase I Consortium||Arcadia, California 91006-3776|