Cixutumumab and Temsirolimus in Treating Young Patients With Solid Tumors That Have Recurred or Not Responded to Treatment
RATIONALE: Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of cixutumumab when given together with temsirolimus in treating young patients with solid tumors that have recurred or not responded to treatment.
Unspecified Childhood Solid Tumor, Protocol Specific
Genetic: gene expression analysis
Genetic: protein expression analysis
Genetic: western blotting
Other: immunologic technique
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of IMC-A12 (Anti-Insulin-Like Growth Factor-I Receptor Monoclonal Antibody) in Combination With CCI-779 (Temsirolimus) in Pediatric Patients With Recurrent or Refractory Solid Tumors|
- Maximum-tolerated dose and recommended phase II dose of cixutumumab and temsirolimus [ Designated as safety issue: Yes ]
- Toxicities according to CTCAE v.3 [ Designated as safety issue: Yes ]
- Pharmacokinetics [ Designated as safety issue: No ]
- Antitumor activity according to RECIST criteria [ Designated as safety issue: No ]
- Biologic activity of cixutumumab, as assessed by changes in IGFR and insulin-receptor expression and phosphorylation [ Designated as safety issue: No ]
- Biologic activity of temsirolimus, as assessed by levels of S6K1, AKT, eIF4G, and associated phosphoproteins [ Designated as safety issue: No ]
- Incidence of IGFR expression as well as mTOR pathway activation [ Designated as safety issue: No ]
|Study Start Date:||November 2008|
|Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
- 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.
- 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.