HGS-ETR2 to Treat Children With Solid Tumors

Summary

Background * HGS-ETR2 is a monoclonal antibody, produced in the laboratory from human genes. * HGS-ETR2 targets a protein called the TRAIL receptor that is located on the surface of some tumor cells. When the TRAIL receptor is activated, it can cause the tumor cell to self-destruct. Objectives: * To determine the highest dose of HGS-ETR2 that can be given safely in children and young adults with cancer. * To study the pharmacology (how the body handles the drug) of HGS-ETR2 by measuring the amount of drug in the bloodstream over time before and after a dose is given to the patient. * To determine if HGS-ETR2 can stop or slow tumor growth. * To determine whether proteins in tumor tissue before treatment can predict whether the tumor will respond to HGS-ETR2 therapy. Eligibility: -Patients 1 to 21 years of age with solid cancers that do not respond to standard therapy. Design: * HGS-ETR2 is given through a vein (intravenously, IV) once every 14 days. Each treatment cycle is 28 days long and consists of two doses of HGS-ETR2. * The dose of HGS-ETR2 is increased in successive small groups of patients until the maximum tolerated dose (highest dose with acceptable side effects) is determined. * During the treatment period, patients have a physical examination at least once a week, and routine blood tests at least twice a week. These tests are done less frequently in later treatment cycles. * Additional blood samples are drawn for immunology and pharmacology studies. * Tests to monitor the size of the tumor (X-rays, CT scans, MRI, PET scans) are done periodically throughout the treatment period. * Patients may continue to receive HGS-ETR2 until unacceptable side effects develop or the tumor grows.

Timeline

Start

2006-12-04

Primary completion

2011-04-28

Completion

2015-10-09

Publications

• Background Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA, et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity. 1995 Dec;3(6):673-82. doi: 10.1016/1074-7613(95)90057-8.
• Background Georgakis GV, Li Y, Humphreys R, Andreeff M, O'Brien S, Younes M, Carbone A, Albert V, Younes A. Activity of selective fully human agonistic antibodies to the TRAIL death receptors TRAIL-R1 and TRAIL-R2 in primary and cultured lymphoma cells: induction of apoptosis and enhancement of doxorubicin- and bortezomib-induced cell death. Br J Haematol. 2005 Aug;130(4):501-10. doi: 10.1111/j.1365-2141.2005.05656.x.
• Background Younes M, Georgakis GV, Rahmani M, Beer D, Younes A. Functional expression of TRAIL receptors TRAIL-R1 and TRAIL-R2 in esophageal adenocarcinoma. Eur J Cancer. 2006 Mar;42(4):542-7. doi: 10.1016/j.ejca.2005.11.013. Epub 2006 Jan 19.
• Merchant MS, Geller JI, Baird K, Chou AJ, Galli S, Charles A, Amaoko M, Rhee EH, Price A, Wexler LH, Meyers PA, Widemann BC, Tsokos M, Mackall CL. Phase I trial and pharmacokinetic study of lexatumumab in pediatric patients with solid tumors. J Clin Oncol. 2012 Nov 20;30(33):4141-7. doi: 10.1200/JCO.2012.44.1055. Epub 2012 Oct 15.

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