International Trial Assesses Celecoxib in Pediatric FAP Patients

A Cleveland Clinic-led trial is the first to assess the impact of an anti-inflammatory drug on disease progression in children with familial adenomatous polyposis (FAP) on an international level.

FAP is an inherited colorectal cancer syndrome affecting 1 in 13,000. Hundreds to thousands of polyps develop in the colon, often by age 15. There is no known cure and colectomy is the standard approach to prevent colon cancer, which is inevitable and often occurs by age 40.

Could Celecoxib Help Children?

Carol A. Burke, MD, Director of the Center for Colon Polyp and Cancer Prevention at Cleveland Clinic, led a Phase 3 international trial looking at the safety and efficacy of celecoxib, an anti-inflammatory drug shown to reduce colon polyps in adults, in the treatment of children with FAP.

Cleveland Clinic and the University of Texas MD Anderson Cancer Center collaborated in 2010 on a Phase 1 study assessing the safety and efficacy of celecoxib in children to determine the appropriate dosage. That study, published in the American Journal of Gastroenterology, determined that a daily dose of 16 mg/kg of celecoxib is safe, well tolerated and significantly reduced the number of colorectal polyps in children with FAP.

Examining the Data

This latest Phase 3 study – the first international trial looking at celecoxib in the pediatric population – randomized 106 children, ages 10 to 17, at 18 centers in 13 countries between 2006 and 2013 to assess the drug’s safety and efficacy in preventing colorectal polyps in pediatric patients with FAP. Dr. Burke and her colleagues found that half of the children on celecoxib developed polyps in twice the time period than the children in the placebo arm of the study.

“While celecoxib is not a cure, it is a reasonable adjunct to yearly colonoscopy to prevent polyp progression, and may allow children to delay their surgery to a suitable time or until another agent becomes available,” Dr. Burke says. “For instance, a sophomore in high school may be able to safely delay the need for colon removal until after graduation, when the timing is more elective due to decrease in polyp burden.”

The results of this study were presented at the American College of Gastroenterology (ACG) Annual Scientific Meeting. Dr. Burke, who serves on the ACG Board of Trustees, was recently elected vice president of the organization. She also serves on the board of the Ohio Gastroenterology Society and is a past president of the Collaborative Group of the Americas on Inherited Colorectal Cancer.

Looking ahead

Dr. Burke and her colleagues are now studying drug combinations that have different mechanisms of action in adults, including the anti-inflammatory sulindac in combination with the experimental drug difluormethylornithine (DFMO), which has been shown to reduce polyp growth in the colon. Earlier clinical trials show this drug combination may be more effective than one drug in reducing the number of colon polyps.

For more information, please contact Dr. Burke at 216.444.6864 or burkec1@ccf.org