Cixutumumab and Temsirolimus in Treating Young Patients With Solid Tumors That Have Recurred or Not Responded to Treatment

OBJECTIVES:

Primary

- To estimate the maximum tolerated dose and recommended phase II dose of cixutumumab
administered as an intravenous infusion once weekly in combination with temsirolimus
administered intravenously once weekly in children with refractory solid tumors.

- To define and describe the toxicities of this regimen.

- To characterize the pharmacokinetics of this regimen in children with refractory
cancer.

Secondary

- To preliminarily define the antitumor activity of this regimen within the confines of a
phase I study.

- To assess the biologic activity of cixutumumab by assessing changes in IGFR expression
and phosphorylation and insulin-receptor expression and phosphorylation in peripheral
blood mononuclear cells (PBMNC).

- To assess the biological activity of temsirolimus by measuring levels of S6K1, AKT,
eIF4G, and associated phosphoproteins in PBMNC.

- To assess the incidence of IGFR expression as well as mTOR pathway activation in these
patients.

OUTLINE: This is a multicenter study.

Patients receive cixutumumab IV over 60 minutes and temsirolimus IV over 30 minutes on days
1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of
disease progression or unacceptable toxicity.

Blood samples are collected periodically for pharmacokinetic, pharmacodynamic, immunogenic,
and other correlative studies. Samples are analyzed for IGF-1, IGF-2, IGF-BP3, growth
hormone, insulin, C-peptides; S6K1, AKT, and associated phosphoproteins; and IGF-1R and
insulin-receptor expression and phosphorylation by immunoprecipitation and western
immunoblotting. Tumor tissue studies are conducted to assess the incidence of IGFR
expression as well as mTOR pathway activation.

After completion of study therapy, patients are followed periodically.