NCT00880282

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

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 39 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial is studying the side effects and best dose of cixutumumab when given together with temsirolimus in treating younger patients with solid tumors that have recurred or not responded to treatment. 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.

Detailed description

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and recommended Phase II dose of IMC-A12 (anti-insulin growth factor-1 receptor monoclonal antibody) (cixutumumab) administered as an intravenous infusion once weekly in combination with CCI-779 (temsirolimus) administered intravenously once weekly to children with refractory solid tumors. II. To define and describe the toxicities of IMC-A12 in combination with temsirolimus administered on this schedule. III. To characterize the pharmacokinetics of IMC-A12 in combination with temsirolimus in children with refractory cancer. SECONDARY OBJECTIVES: I. To preliminarily define the antitumor activity of the combination of IMC-A12 and temsirolimus within the confines of a Phase I study. II. To assess the biologic activity of IMC-A12 by assessing: changes in insulin-like growth factor receptor (IGFR) expression and phosphorylation and insulin-receptor expression and phosphorylation in peripheral blood mononuclear cells (PBMNC). III. To assess the biological activity of temsirolimus by measuring levels of phosphorylated (phosphor)-ribosomal protein S6 kinase, 70kDa, polypeptide 1 (S6K1), phosphor-protein kinase B (AKT), phosphor-eukaryotic translation initiation factor 4 gamma, 1 (eIF4G) in PBMNC. IV. To assess the incidence of IGFR expression as well as mechanistic target of rapamycin (mTOR) pathway activation in recurrent or refractory solid tumors of childhood. OUTLINE: Patients receive cixutumumab intravenously (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. After completion of study therapy, patients are followed up periodically.

Conditions

• Unspecified Childhood Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
BIOLOGICAL	cixutumumab	Given IV
DRUG	temsirolimus	Given IV
OTHER	pharmacological study	Correlative studies
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2009-04-01
• Primary completion: 2012-10-01
• First posted: 2009-04-13
• Last updated: 2014-04-29

Locations

23 sites across 2 countries: United States, Canada