The agent, called R1507, is an investigational monoclonal antibody produced by Hoffmann-La Roche that inhibits insulin-like growth factor 1 receptor (IGF-1R). Ewing sarcoma has been linked with mutated genes that promote the production of IGF-1R. Previous phase I studies that included adolescents and young adults demonstrated promising results in Ewing sarcoma patients with treatment-resistant (refractory), progressive disease who had failed multiple standard and "salvage" therapies. In some cases, there have been complete responses to IGF-1R blockers in such high-risk patients.

Dr. Lee Helman, NCI's scientific director for clinical science and a noted expert in pediatric sarcomas, received numerous calls about these early results and met with his colleagues as part of the Sarcoma Alliance for Research through Collaboration several times to hear presentations from companies, including Roche, about their IGF-1R blocker compounds for use in a planned phase II study in children and adults aged 12 years and older with relapsed or refractory Ewing sarcoma. They selected R1507 for the current study and will expand this treatment to several other pediatric and adult sarcomas, including rhabdomyosarcoma and osteosarcoma.

"Because these are rare tumors, no single institution can do a large enough study - nor can any one country," Dr. Helman commented, noting that there are only about 200 new cases of Ewing sarcoma diagnosed in the United States each year. "We very quickly engaged our European colleagues who we've collaborated with on a number of previous projects."

The trial got under way at several U.S. cancer centers in December and has already accrued about 30 patients. The study will open shortly at the NIH Clinical Center and at sites in France, Italy, Germany, and the United Kingdom next month.

Dr. Herbert Juergens, professor of pediatric hematology and oncology at the University of Muenster, which is one of the study sites in Germany, said that progress in treatment of Ewing sarcoma "has become very slow" in recent years. Research has achieved long-term survival rates of about 70 percent with standard treatments, which include intensive chemotherapy and "local" interventions of radiation and surgery. "Since then, we seem to have exhausted the intensity of chemotherapy we can administer to the patients," he continued. Instead, hope has focused on finding therapies that target specific receptors in these tumors.

The international trial to test R1507 for Ewing sarcoma "is wonderful," Dr. Juergens said. To find sufficient patients with relapsing disease to produce statistically significant data, he added, "You need to work across the Atlantic Ocean."

Dr. Helman noted, "Over the next several years, we'll have to work hard to see if we can identify genomic profiles or markers that will predict those patients who are more likely to respond to IGF-1R inhibitors and figure out how we might move this to frontline therapy, because it might minimize toxicity" compared with current chemotherapy.