Clinician-investigators and researchers at Riley Children’s Health are set to launch a prospective clinical trial aimed at identifying novel agents for the treatment of relapsed/refractory (R/R) sarcomas in children and young adults.
In a largely untapped area of study in pediatric sarcoma, the proof-of-concept, grant-funded trial at Riley Children’s will determine the feasibility of using the tumor proteomic profile to pinpoint potential therapies for individual patients.
“There is a critical unmet need in treatment for pediatric and AYA (adolescent and young adult) sarcoma patients,” said pediatric oncologist Marissa Just, MD, who is leading the clinical trial with Brian Weiss, MD, division chief of pediatric hematology, oncology and stem cell transplant at Riley Children’s. “There are very few open Phase 1 and Phase 2 trials for these patients, and frankly, once patients fail the standard of care, there are very limited options available for long-term survival.”
In a departure from conventional tumor sequencing, the trial will profile the tumor kinome with the goal of identifying existing FDA-approved drug therapies that may be helpful in treating the patient’s disease. When the investigator-initiated trial is underway, young adult patients with R/R sarcoma will receive treatment with a personalized selection of one of the 82 currently approved kinase inhibitors based on a functional kinome analysis. The team will leverage two innovative proteomic approaches, in conjunction with clinical genomics, to define the functional kinome of sarcoma tumor specimens at initial diagnosis and then upon relapse following standard-of-care therapy.
In addition to Drs. Just and Weiss, the clinical trial team includes leading pediatric cancer physician-scientists Wade Clapp, MD, chair of the Indiana University School of Medicine Department of Pediatrics, and Steven Rhodes, MD, PhD. The study also relies on the expertise of Steve Angus, PhD, a researcher in the Herman B Wells Center for Pediatric Research at Riley Children’s. Dr. Angus uses proteomics and genomics to characterize adaptive responses of tumors to targeted kinase inhibitors.
“Committed to advancing treatment for complex cancers, we’re working to bridge the gap between basic science and what we see every day in our clinic,” said Dr. Weiss. “Strong collaboration is key to embarking on a clinical trial like this and with the Wells Center and the IU cancer center just steps away from Riley Children’s, we have an environment that’s hard to beat for this kind of novel research.”
The clinical trial, projected to launch in 2025 with six to 10 patients, is funded by the Indiana Biosciences Research Institute, the Purdue Institute for Cancer Research/Tyler Trent Pediatric Cancer Research Center and the IU Melvin and Bren Simon Comprehensive Cancer Center/Hunnicut Family Fund. Representatives from these organizations, including Drs. Just and Weiss, convened in spring 2024 to discuss strategies for addressing the gaps in pediatric sarcoma research.
