A new clinical trial led by the Penn State College of Medicine-based Beat Childhood Cancer Research Consortium will evaluate whether the drug eflornithine (DFMO) can help prevent relapse and improve outcomes for patients with Ewing sarcoma and osteosarcoma - two aggressive bone cancers that have seen few meaningful treatment advances in decades, according to Giselle Saulnier Sholler, chair and founder of the consortium.
Sholler, also the Four Diamonds Endowed Chair for Pediatric Oncology Research in the Department of Pediatrics and a professor of neuroscience and experimental therapeutics, said the trial aims to build on recent progress involving DFMO. In 2023, the drug received U.S. Food and Drug Administration approval to help reduce the risk of relapse in patients with high-risk neuroblastoma - a milestone achieved through research led by Sholler and the consortium team.
DFMO works by blocking an enzyme - a type of protein that accelerates biological reactions - called ornithine decarboxylase (ODC), which plays a key role in cell growth and division. By inhibiting the enzyme, the drug may slow or stop the growth of cancer cells.
"The DFMO approval represented years of collaborative work focused on improving outcomes for children with neuroblastoma," Sholler said. "What is especially exciting about the new clinical trial is the opportunity to extend what we've learned about DFMO to help children and young adults facing other devastating cancers. Seeing this science move beyond neuroblastoma and into additional pediatric and young adult populations is exactly why we pursue translational research."
The Phase II clinical trial, known as BCC023, is expected to begin enrolling patients this month through the consortium's international network of more than 50 hospitals. The study will assess the safety and effectiveness of DFMO in combination with standard treatments, as well as DFMO used alone in certain patient groups, for Ewing sarcoma and osteosarcoma.
These rare but aggressive cancers most often affect children, adolescents and young adults. While survival rates have improved for some pediatric cancers in recent decades, outcomes for patients with relapsed or metastatic sarcomas remain poor, according to David Loeb, pediatric oncologist at Children's Hospital at Montefiore and study chair of the BCC023 study.
"There have been few recent advancements in standard of care for Ewing sarcoma and osteosarcoma," Loeb said. "Based on results from our clinically relevant translational mouse model, we anticipate that DFMO will prevent future disease relapse in children and young adults with osteosarcoma and Ewing sarcoma once radiographically free of disease. It is incredibly gratifying to see discoveries made at the bench move forward into clinical studies that may ultimately improve outcomes for patients."
The BCC023 study is the next step in exploring the broader potential of DFMO while advancing the consortium's missions to develop new treatment options for pediatric solid tumors, Loeb said. The trial is designed as a "basket trial," allowing researchers to evaluate DFMO across several different patient groups within a single clinical trial. Through this multicenter effort across the consortium, the trial is expected to enroll approximately 369 patients. Researchers will evaluate several outcomes, including event-free survival, relapse-free survival and disease control at 12 months.
"This new trial represents the next step in expanding the potential of DFMO to help children and young adults facing other difficult-to-treat cancers," said Karen Kim, dean of Penn State College of Medicine. "Through collaborative research networks like the Beat Childhood Cancer Research Consortium, we are able to bring together expertise from across institutions to accelerate the development of new therapies for pediatric cancers that urgently need better treatment options."
