Although there have been great strides in treating pediatric cancer, it remains the leading cause of death by disease among children. In addition, more than 95 percent of childhood cancer survivors have significant health-related issues because of the toxicity of current treatment options. Yet just 4 percent of government spending on cancer goes to pediatric cancer.1
That’s why the Sunshine Project is so important. The project, part of the National Pediatric Cancer Foundation, brings together more than 20 children’s hospitals, including Children’s of Alabama, with the goal of streamlining the process required to bring new, less toxic, more effective pediatric oncology drugs to clinical practice.
Children’s joined the consortium in 2020 and is already participating in several novel studies for some of the worst pediatric cancers. The ultimate goal is to “provide hope to families,” said Children’s oncologist Elizabeth Alva, M.D.
One such trial is for patients newly diagnosed with metastatic fusion-positive rhabdomyosarcoma, which has a three-year, event-free survival rate of just 6 percent. “Traditionally, we inundate these patients with very intensive therapy,” said pediatric oncologist Katie Metrock, M.D., but outcomes are still dismal. Research has traditionally focused on intensifying that therapy, but sometimes that just leads to greater toxicity without improving outcomes, said Dr. Alva.
This uniquely designed study, called the EVOLUTION trial, is based on evolutionary theories around adaptation and resistance. Patients will be enrolled into one of four arms based on shared decision-making between the family and clinicians—not randomization. The first arm is standard of care. The second arm is “first strike therapy,” which Dr. Alva compares to a “meteor hitting the Earth and killing all the dinosaurs.” This approach addresses the hypothesis that children relapse because once the chemo-sensitive cells are gone, a more resistant population emerges. “So the first-strike theory is to get rid of everything,” she said.
A third arm focuses on maintenance, or a “second strike”: providing the standard of care until the patient is in remission and then switching to a less-intense maintenance therapy to keep those resistant cells at bay while restoring quality of life.
The fourth arm provides adaptive therapy. This means starting with standard chemotherapy that starts and stops based on response and adaptive timing of therapy, with a goal of increased time to progression rather than complete remission.
Children’s is also participating in a phase 2 study evaluating the use of digoxin, a decades-old drug typically used in patients with heart failure, for patients with recurrent/refractory medulloblastoma. The drug was identified as potentially beneficial in laboratory and animal studies.
“It is exciting to think that there are well-known drugs that can be repurposed to help treat various cancers,” said Dr. Metrock. “Our hope is that the tumors will show response to digoxin, and it could potentially be added to other up-front regimens in the future.” While the drug is well tolerated in children,” she said, “we haven’t used it in this heavily pretreated population, so we need to see how our patients do with it.”
Two other trials are exploring immunotherapy. One is testing the immunotherapy nivolumab in combination with azacitidine for children with recurrent, refractory osteosarcoma. The other is exploring a vaccine made from the patient’s own cancer cells designed to trigger the immune system to target the cancer for destruction in children with high-grade gliomas. Trials such as these are coordinated by the Clinical Trials Office at Children’s of Alabama, which was established in 2019 to increase access to new therapies for Alabama children, thanks to a lead gift from the Hugh Kaul Foundation.
Projects like the Sunshine Project are desperately needed, said Dr. Alva. “Unfortunately, pediatric cancer doesn’t get the same degree of funding as adult cancer. It’s rare, but when it strikes in a pediatric population, so many more years of life are lost.”
1 National Pediatric Cancer Foundation. Facts about Childhood Cancer. Available at: https://nationalpcf.org/facts-about-childhood-cancer/.