When a clear, curative pathway is not available for pediatric cancers that relapse, families often will turn to new, experimental treatments being studied by The Children’s Oncology Group with hopes of exploring other options to care for their children. A new research opportunity under development as part of its Project:EveryChild, called Project:EveryChild Pediatric MATCH (Molecular Analysis for Therapy Choice), aims to use the power of precision medicine to potentially provide investigational therapies for some children with advanced cancers.
The Children’s Oncology Group, a collaboration of more than 220 leading children’s hospitals, universities, and cancer centers from across the globe — including The Children’s Hospital of Philadelphia — is the world’s largest organization devoted exclusively to childhood and adolescent cancer research.
Each year, nearly 13,500 children and teens are diagnosed with numerous types of cancer. Within those types of cancer, there are multiple subsets of disease. Some are harder to treat than others. Scientists suspect that the tumors involved in those stubborn cases may have different genetic alterations that help them to resist standard therapy and begin to grow.
“Pediatric MATCH will try to match genomic changes in certain children’s cancers with drugs that are either approved for adult cancers or with drugs that are still under investigation and not yet approved,” said Peter Adamson, MD, chair of the Children’s Oncology Group and a pediatric oncologist at CHOP. “The other goal is to try to understand if there is a genomic basis for when our treatments fail and how the cancers may have changed from the time of original diagnosis.”
While Pediatric MATCH is still under development, Dr. Adamson expects that the study enrollment will include about 300 children each year with advanced cancers that have progressed on standard therapy. Although only some of these children will have cancers that can be matched to a new drug, a significant aspect of Pediatric MATCH is those children with matches will be assigned to a phase II research protocol based on the genetic abnormality that seems to be fueling their disease progression, not the type of cancer.
After the child undergoes a tumor biopsy at relapse, some of the tissue will be sent to a centralized center for specific tests that may include next-generation DNA sequencing. Once investigators identify the tumor’s genomic changes and characteristics, they will sort through a group of 20 to 25 selected targeted drugs to see if one has shown some efficacy against tumors with the same genetic alterations. Should a match be found, the child will then be able to receive that drug to see if it is of some potential benefit.
“What we know to date about the genomics of cancer at diagnosis and at relapse is that perhaps there are somewhere in the order of about 15 percent of cancers that may have a finding for which we may have a drug,” Dr. Adamson said.
In a unique arrangement, the Pediatric MATCH trial is a combined effort of the Children’s Oncology Group, the National Cancer Institute (NCI), and a range of pharmaceutical companies that already have committed to providing drugs to be tested in an adult NCI MATCH Trial slated to begin this year. Dr. Adamson anticipates that many of this similar counterpart trial’s pharmaceutical agreements will carry over to Pediatric MATCH. New drugs could be added to the trials over time.
“That is of great importance to this project because all childhood cancers are rare diseases, and there generally isn’t an economic model for pharmaceutical companies to study childhood cancers,” Dr. Adamson said.
While the Children’s Oncology Group has partnered successfully in the past with companies to provide two different experimental drugs in a single research trial, Pediatric MATCH will be a significant leap beyond that model. Dr. Adamson estimates up to 10 companies will be participating in Pediatric MATCH, and each will receive information that will advance knowledge, may benefit children, and also could help the companies to accelerate their drug development.
“We hope that we will be able to see signals of efficacy that these drugs are working that would then lead to potentially additional trials that become disease-specific for that drug,” Dr. Adamson said. “Well-defined genomic testing may one day provide a lead to having a portfolio of drugs that may be of benefit to the child.”
The Pediatric MATCH study team also will share tumor analysis results with the child’s cancer specialists to help them guide the family’s treatment choices. In addition, the tissue samples will be highly valuable to future researchers as they try to explain the basis of cancer treatment failure and relapse.
“If we find that a certain pathway is very important for a disease or subset of diseases, we can build upon that and perhaps bring new treatments into that disease area, not only for relapsed cancer, but potentially to move those treatments earlier into therapy for appropriate populations,” said Dr. Adamson, who also is a professor of pediatrics and pharmacology at the Perelman School of Medicine at the University of Pennsylvania.
Pediatric MATCH is a high priority for the Children’s Oncology Group, Dr. Adamson said, with five working groups focused on an aggressive timeline of launching the trial toward the beginning of 2016.