Penn State Launches Phase II Trial of DFMO for Pediatric Bone Cancers Following FDA Approval in Neuroblastoma
Key Insights
The Beat Childhood Cancer Research Consortium (search) has launched a Phase II clinical trial (BCC023) to evaluate eflornithine (DFMO) for preventing relapse in children and young adults with Ewing sarcoma (search) and osteosarcoma (search).
DFMO received FDA approval in 2023 for high-risk neuroblastoma (search) relapse prevention and works by inhibiting ornithine decarboxylase (search) (ODC (search)), an enzyme crucial for cancer cell growth and division.
The basket trial will enroll approximately 369 patients across 50+ hospitals internationally, assessing DFMO's safety and effectiveness both alone and combined with standard treatments.
The Penn State College of Medicine (search)-based Beat Childhood Cancer Research Consortium (search) has initiated a Phase II clinical trial to evaluate whether eflornithine (DFMO) can prevent relapse and improve outcomes for pediatric patients with aggressive bone cancers. The study, designated BCC023, represents a significant expansion of DFMO's therapeutic potential following its FDA approval for neuroblastoma (search) in 2023.
Building on Neuroblastoma Success
DFMO received U.S. Food and Drug Administration approval in 2023 to help reduce the risk of relapse in patients with high-risk neuroblastoma (search), a milestone achieved through research led by Giselle Saulnier Sholler, chair and founder of the consortium. Sholler, who serves as the Four Diamonds Endowed Chair for Pediatric Oncology Research in the Department of Pediatrics and professor of neuroscience and experimental therapeutics, emphasized the significance of extending this success to other pediatric cancers.
"The DFMO approval represented years of collaborative work focused on improving outcomes for children with neuroblastoma (search)," 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."
Mechanism of Action and Target Diseases
DFMO works by blocking ornithine decarboxylase (search) (ODC (search)), an enzyme that plays a key role in cell growth and division. By inhibiting this enzyme, the drug may slow or stop the growth of cancer cells. The current trial will focus on Ewing sarcoma (search) and osteosarcoma (search), two rare but aggressive bone cancers that most often affect children, adolescents and young adults.
These cancers have seen few meaningful treatment advances in decades, according to the research team. While survival rates have improved for some pediatric cancers in recent decades, outcomes for patients with relapsed or metastatic sarcomas remain poor.
Trial Design and Enrollment
The BCC023 study is designed as a "basket trial," allowing researchers to evaluate DFMO across several different patient groups within a single clinical trial. 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.
Patient enrollment is expected to begin this month through the consortium's international network of more than 50 hospitals. The multicenter effort is projected to enroll approximately 369 patients. Researchers will evaluate several outcomes, including event-free survival, relapse-free survival and disease control at 12 months.
Preclinical Foundation
David Loeb, pediatric oncologist at Children's Hospital at Montefiore (search) and study chair of the BCC023 study, highlighted the promising preclinical data supporting the trial. "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 (search) and Ewing sarcoma (search) once radiographically free of disease," Loeb said.
"There have been few recent advancements in standard of care for Ewing sarcoma (search) and osteosarcoma (search)," Loeb noted. "It is incredibly gratifying to see discoveries made at the bench move forward into clinical studies that may ultimately improve outcomes for patients."
Collaborative Research Impact
Karen Kim, dean of Penn State College of Medicine (search), emphasized the importance of collaborative research networks in advancing pediatric cancer treatment. "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," Kim said. "Through collaborative research networks like the Beat Childhood Cancer Research Consortium (search), 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."
The BCC023 study represents the next step in exploring the broader potential of DFMO while advancing the consortium's mission to develop new treatment options for pediatric solid tumors. The trial's basket design allows for efficient evaluation of the drug across multiple patient populations, potentially accelerating the path to improved treatments for these challenging cancers.