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

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. * Participants will have additional physical exams, blood and urine tests, and imaging studies regularly during each treatment cycle. * Participants will be followed at regular intervals after the end of the study to collect tumor response and progression data....

Timeline

Start

2010-07-28

Primary completion

2012-04-04

Completion

2012-04-04

Publications

• Background Burtrum D, Zhu Z, Lu D, Anderson DM, Prewett M, Pereira DS, Bassi R, Abdullah R, Hooper AT, Koo H, Jimenez X, Johnson D, Apblett R, Kussie P, Bohlen P, Witte L, Hicklin DJ, Ludwig DL. A fully human monoclonal antibody to the insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits human tumor growth in vivo. Cancer Res. 2003 Dec 15;63(24):8912-21.
• Background Boulay A, Zumstein-Mecker S, Stephan C, Beuvink I, Zilbermann F, Haller R, Tobler S, Heusser C, O'Reilly T, Stolz B, Marti A, Thomas G, Lane HA. Antitumor efficacy of intermittent treatment schedules with the rapamycin derivative RAD001 correlates with prolonged inactivation of ribosomal protein S6 kinase 1 in peripheral blood mononuclear cells. Cancer Res. 2004 Jan 1;64(1):252-61. doi: 10.1158/0008-5472.can-3554-2.
• Background Majumder PK, Febbo PG, Bikoff R, Berger R, Xue Q, McMahon LM, Manola J, Brugarolas J, McDonnell TJ, Golub TR, Loda M, Lane HA, Sellers WR. mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med. 2004 Jun;10(6):594-601. doi: 10.1038/nm1052. Epub 2004 May 23.

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