Clinical Trial: A Phase I Study of IMC-A12 in Combination With Temsirolimus in Pediatric Patients With Recurrent or Refractory Solid Tumors

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

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

Brief Summary:

Background:

- IMC-A12 is an experimental substance designed to inhibit a protein called Type I Insulin-Like Growth Factor Receptor (IGF-1R), which can be found on cancer cells and can promote cancer growth. Temsirolimus is a drug that the U.S. Food and Drug Administration has approved to treat advanced renal cell carcinoma in adults. Researchers do not know if the combination of IMC-A12 and temsirolimus will work in children, but want to determine whether these two drugs may be an effective treatment for recurrent tumors.

Objectives:

  • To determine the safety and effectiveness of IMC-A12 and temsirolimus in treating children and adolescents with solid tumors.
  • To determine possible side effects of the combination of IMC-A12 and temsirolimus.

Eligibility:

- Children and adolescents between 12 months and 21 years of age who have solid tumors that have not responded to or have relapsed after standard treatment.

Design:

  • Participants will be screened with a medical history, physical examination, and imaging studies.
  • Participants will receive IMC-A12 and temsirolimus in 28-day cycles of treatment. IMC-A12 will be given as an infusion over 1 hour, once a week, for 4 weeks. Temsirolimus will also be given after IMC-A12 over 30 minutes, once a week, for 4 weeks.
  • Participants may continue to receive IMC-A12 and temsirolimus for up to 2 years unless serious side effects develop or the treatment stops being effective.

    Detailed Summary:

    Background

    • IMC-A12 is a fully recombinant IgG1monoclonal antibody to the insulin-like growth factor receptor (IGFR). It acts as an antagonist of IGF-1 and IGF-2 ligand binding and blocks ligand binding to IGF-1R and inhibits downstream signaling of the two major insulin-like growth factor pathways: MAPK and PI3K/AKT.
    • Temsirolimus is a small molecule inhibitor of mTOR, which like rapamycin and everolimus forms a complex with FK506-binding protein (FKBP)12 and mTOR, inhibiting mTOR and leading to anti-proliferative effects, including G1 phase cell cycle arrest and apoptosis.
    • Inhibition of mTOR signaling leads to upregulation of IGF-1R signaling which leads to activation of the PI3K/AKT/mTOR pathway. Pediatric pre-clinical models have demonstrated synergistic anti-tumor effects combining IGF-1R antibodies and mTOR inhibitors.

    Objectives

    • To determine the maximum tolerated dose (MTD) and recommended Phase II dose of IMC-A12 (anti-insulin growth factor-1 receptor monoclonal antibody) administered as an intravenous infusion once weekly in combination with temsirolimus administered intravenously once weekly to children with refractory solid tumors.
    • To define the toxicities of the combination regimen and characterize the pharmacokinetics of IMC-A12 in combination with temsirolimus in this patient population.
    • Secondary objectives include defining in a preliminary fashion antitumor activity, assessing biologic activity of IMC-A12 and temsirolimus and assessing the incidence of IGFR expression and mTOR pathway activation in recurrent or refractory solid tumors of childhood.

      • Sponsor: National Cancer Institute (NCI)

      Current Primary Outcome:

      • To determine the MTD and recommended Phase II dose of IMC-A12 (anti-IGFR monoclonal antibody) IV once weekly in combination with temsirolimus IV weekly to children with refractory solid tumors.
      • To define toxicities and characterize pharmacokinetics.


      Original Primary Outcome:

      Current Secondary Outcome: Define in a preliminary fashion antitumor activity, assess biologic activity of IMC-A12 and temsirolimus and assess the incidence of IGFR expression and mTOR pathway activation in recurrent or refractory solid tumors of childhood.

      Original Secondary Outcome:

      Information By: National Institutes of Health Clinical Center (CC)

      Dates:
      Date Received: August 14, 2010
      Date Started: July 28, 2010
      Date Completion: April 4, 2012
      Last Updated: January 24, 2017
      Last Verified: April 4, 2012