News Release

Wednesday, May 16, 2012

Drug used in NIH-supported trial shows benefit in children with previously treated cancers

Young patients with some types of advanced cancer, for whom standard treatment had failed, had their tumors disappear during treatment with a drug that both targets and blocks a protein associated with their disease. These findings are from a Phase I, multicenter trial, led by investigators from the Children's Oncology Group (COG), and supported by the National Cancer Institute (NCI), part of the National Institutes of Health.

Encouraging results, with few side effects, were found in children and adolescents, particularly those with anaplastic large cell lymphoma (ALCL), a type of blood cancer, and neuroblastoma, a nerve cancer arising most often in the adrenal gland and chest, according the research. Results of the Phase I trial were released May 16, 2012, by the American Society of Clinical Oncology (ASCO). The study will be presented at the ASCO 2012 meeting in Chicago on June 2, 2012.

The drug tested in this Phase 1, or early stage trial, is crizotinib (trade name XAKORI, by Pfizer). Crizotinib works by blocking the activity of a protein called anaplastic lymphoma kinase, or ALK, and it is effective in adults whose tumors have alterations in the ALK gene that increase the activity of the ALK protein. Studies have shown that adults with non-small cell lung cancer (NSCLC) harboring ALK gene alterations can be successfully treated with crizotinib. The drug is approved by the U.S. Food and Drug Administration for treating such patients. ALK gene alterations are present in nearly all children with ALCL and in about 10 percent of children with neuroblastoma. ALK gene alterations also occur occasionally in other childhood cancers.

"There is a major opportunity to personalize therapy for children with neuroblastoma and anaplastic large cell lymphoma by providing a relatively non-toxic drug that may allow us to lower the doses of conventional chemotherapy in the very near future," said Yael P. Mosse, M.D., the COG study chair and an assistant professor of pediatrics at The Children's Hospital of Philadelphia.

This COG Phase 1 trial included 70 participants, whose average age was 10 years (the patients ranged from 1 to 21 years of age). At admission, tumor tissue was tested for the presence of ALK gene alterations.

The COG investigators started the trial by providing dosages of crizotinib to their patients that were lower than those used in adults with NSCLC. The children and adolescents in this trial took crizotinib by mouth twice a day for 28 days and were allowed to continue the drug longer if their disease did not progress and if there were no signs of unacceptable toxicity. The investigators were able to safely increase the crizotinib dose through six dose levels with minimal toxicity, to a dose that exceeds that used in adults.

The researchers monitored study participants for changes in their tumor size. Among the eight patients with ALCL enrolled, seven showed complete responses, i.e., complete disappearance of their tumor. Of the 27 patients with neuroblastoma, three have had complete responses (two are known to have an ALK mutation) and seven have had no disease progression. These patients have remained on therapy between nine months to more than two years without progression. Seven patients with inflammatory myofibroblastic tumor, which is a rare form of sarcoma that commonly has ALK gene alterations, remain on therapy, with the majority showing benefit.

“The remarkable aspects of this trial are the number of complete responses observed among these children and adolescents and how well the treatment was tolerated,” said Malcolm Smith, M.D., program director, NCI, for the COG Phase 1 Consortium. “Learning how to best use crizotinib in newly diagnosed patients whose tumors have ALK gene alterations is now a high priority, as this could lead to improved survival for these patients.”

The COG is developing additional studies in which crizotinib will be combined with chemotherapy in patients with ALCL and neuroblastoma. To find a COG trial site or to learn more about the group, please go to

This study was supported by NCI grant U01-CA97452.

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