A first-in-humans clinical trial for children with relapsed or refractory neuroblastoma has opened at American Family Children's Hospital (AFCH) and is being conducted by researchers at University of Wisconsin School of Medicine and Public Health. Neuroblastoma is one of the most common solid tumors in children. Patients who are classified as "high-risk" (about 40 percent of those diagnosed) have less than a 50 percent survival rate.

131I-MIBG, a type of molecular targeted radiotherapy, has been used for many years to treat children with relapsed neuroblastoma. American Family Children's Hospital is one of about 25 centers in the United States capable of providing this therapy. While the treatment is effective, it is not curative, so significant effort has been expended devising ways to improve the durability of responses achieved with this agent.

American Family Children's Hospital
American Family Children's Hospital

This trial, which initially opened in England, is investigating the combination of targeted radiation therapy with immunotherapy to treat children with relapsed or refractory neuroblastoma. The concept is based, in part, on laboratory work conducted at University of Wisconsin–Madison by Paul Sondel, MD, PhD, professor of pediatrics and human oncology, and Zachary Morris, MD, PhD, assistant professor of human oncology. Sondel and Kenneth DeSantes, MD, professor of pediatrics, are the trial’s co-principal investigators.

The pre-clinical research in mice showed that the combination of radiation therapy and immunotherapy was curative, whereas the use of either treatment was not. This new pediatric trial combines 131I-MIBG with an antibody that recognizes neuroblastoma and focuses the patients’ immune system on the cancer.  A third drug, nivolumab, is administered in order to prevent the tumor from shielding itself against the immunologic attack, thereby increasing the number of cancer cells killed by the immune system and improving the possibility of benefit.

“We are delighted to get this clinical trial, which is a great example of ‘bench to bedside’ research, up and running at AFCH,” said DeSantes. “We hope this treatment will offer new hope to children with relapsed neuroblastoma, who currently face a dismal prognosis.”

The UW Pediatric Hematology, Oncology and Bone Marrow Transplant program is collaborating with three other centers in Europe on this pioneering first-in-humans clinical trial. American Family Children's Hospital is the first and only center in the United States to offer this therapy.