Landmark Transatlantic Trial

Grant awarded to Children’s Hospital of Philadelphia (CHOP) and Gustave Roussy in Paris to support Phase 3 clinical trial developed by the Children’s Oncology Group (COG) and the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN)representing first-ever collaboration between these North American and European neuroblastoma consortia

Today Solving Kids' Cancer UK and six partner charities have awarded a grant to Children’s Hospital of Philadelphia (CHOP) and Gustave Roussy in Paris, France in a landmark in paediatric oncology research. The grant is the result of an international partnership led by Solving Kids’ Cancer UK and Solving Kids’ Cancer (US) with Band of ParentsJoining Against Cancer in Kids (J-A-C-K)Ronan Thompson FoundationWade’s Army and Zoé4life and will support parallel Phase 3 clinical trials developed by the Children’s Oncology Group (COG) and the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN). This is the first-ever transatlantic collaboration between the two North American and European paediatric cancer consortia, and will focus on neuroblastoma, a rare and deadly form of childhood cancer.  

Yael Mossé, MD, a physician-scientist who focuses on neuroblastoma in CHOP’s Cancer Center, will co-lead this collaboration with COG alongside Dominique Valteau-Couanet, MD, PhD, the division chief of Pediatric Oncology at Gustave Roussy on behalf of SIOPEN. 

“This exciting collaboration is an important step in developing better treatments for children with neuroblastoma,” said Dr. Mossé. “Only one new drug has been approved by the FDA for neuroblastoma in the past 30 years. We hope this collaboration between North American and European researchers will bring more targeted therapies to children newly diagnosed with this disease.” 

“It is a unique opportunity to demonstrate the impact of such targeted therapies in this disease,” said Dr. Valteau-Couanet. “The collaboration is the result of a confident relationship developed between our two groups during the last decade. It is a first step of a collaboration that will help to answer questions that could not be solved otherwise”.

“International collaboration is vital to move things forward rapidly for children with rare cancers like neuroblastoma, but it is not without challenge. We are extremely proud to be driving innovation that provides real hope to children and families who are shattered by a neuroblastoma diagnosis. We are also very thankful to the pioneering team of researchers who have made it possible.”

Nick Bird, Chair of Trustees

The study, known as TITAN – Transatlantic Integration Targeting ALK in Neuroblastoma – will see a targeted drug introduced to frontline treatment for children, with the hope of dramatically increasing survival rates in this group of patients. This landmark collaboration between cooperative research groups in Europe and North America is the first time the pediatric consortia on both sides of the Atlantic have worked together on a trial. 

Neuroblastoma is the most common pediatric cancer diagnosed in infancy, with approximately 90 percent of children with the disease diagnosed before the age of five. In North America and Europe, some 1,500 children are diagnosed with severely malignant, high-risk neuroblastoma each year, which requires intense and grueling treatment. Fewer than half of those with high-risk disease live more than five years after diagnosis, and those who do survive often suffer lifelong side effects, including hearing loss, learning disabilities, and secondary cancers. 

In order to develop a more effective and less toxic treatment for neuroblastoma, clinical trials within COG and SIOPEN will target mutations in the ALK gene, which are found in around 14 percent of patients with newly diagnosed neuroblastoma and have recently been implicated in relapses of the disease. Through a partnership with Pfizer Pharmaceuticals and the New Approaches to Neuroblastoma Therapy (NANT), researchers at CHOP led by Mossé’s laboratory have discovered a highly specific and potent ALK inhibitor, lorlatinib, a drug currently used to treat lung cancer that would impede the pro-cancer activities of these ALK mutations and potentially have a significant impact in neuroblastoma patients.  

In parallel Phase 3 clinical trials within COG in North America and SIOPEN in Europe, researchers hope to use lorlatinib to substantially improve survival for patients with newly diagnosed high-risk neuroblastoma whose tumors harbor an activated ALK gene mutation. The TITAN collaboration will involve simultaneous evaluation of the addition of lorlatinib to both COG’s and SIOPEN’s high-risk neuroblastoma treatment regimens, merging the data with the aim of accelerating lorlatinib approval if the drug proves effective.

“This is a landmark step in clinical research for children with neuroblastoma. With paediatric cancer hugely underfunded in comparison to adult cancer, there is an urgent need for breakthrough treatments for the most difficult-to-cure childhood cancers like neuroblastoma.

This trial has the potential to accelerate the discovery of a new treatment and lay the foundation for future collaborations of this nature.”

Professor Andy Pearson, MD, Chair of the Solving Kids’ Cancer UK Scientific Advisory Board