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
- 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
- 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
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.
Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose and recommended phase II dose of cixutumumab and temsirolimus
Maryam Fouladi, MD
Children's Hospital Medical Center, Cincinnati
United States: Food and Drug Administration
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Children's Hospital of Orange County||Orange, California 92668|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Children's Memorial Hospital - Chicago||Chicago, Illinois 60614|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|Midwest Children's Cancer Center at Children's Hospital of Wisconsin||Milwaukee, Wisconsin 53226|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas||Dallas, Texas 75390|
|Baylor University Medical Center - Houston||Houston, Texas 77030-2399|
|Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|C.S. Mott Children's Hospital at University of Michigan Medical Center||Ann Arbor, Michigan 48109-0286|
|Masonic Cancer Center at University of Minnesota||Minneapolis, Minnesota 55455|
|Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis||St. Louis, Missouri 63110|
|Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center||New York, New York 10032|
|Knight Cancer Institute at Oregon Health and Science University||Portland, Oregon 97239-3098|
|Children's Hospital of Pittsburgh of UPMC||Pittsburgh, Pennsylvania 15213|
|Riley's Children Cancer Center at Riley Hospital for Children||Indianapolis, Indiana 46202-5225|
|UAB Comprehensive Cancer Center||Birmingham, Alabama 35294|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|