Cixutumumab and Temsirolimus in Treating Younger Patients With Solid Tumors That Have Recurred or Not Responded to Treatment
Condition: Unspecified Childhood Solid Tumor, Protocol Specific
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): cixutumumab; temsirolimus; pharmacological study; laboratory biomarker analysis
Intervention type(s): Biological; Drug; Other; Other
Intervention description(s): Given IV; Given IV; Correlative studies; Correlative studies
Other intervention name(s): anti-IGF-1R recombinant monoclonal antibody IMC-A12; IMC-A12; CCI-779; cell cycle inhibitor 779; Torisel; pharmacological studies
Intervention MeSH terms: Sirolimus; Temsirolimus; MTOR Inhibitors; Antibodies, Monoclonal
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment