Molecularly Guided Phase 2 Umbrella Trial for Children, Adolescents, and Young Adults Newly Diagnosed with High-Grade Glioma, Including Diffuse Midline Glioma
Abstract
Brain and spine tumors are the leading cause of cancer-related death in children, adolescents, and young adults. Outcomes for pediatric and young adult patients diagnosed with high-grade gliomas (HGG) (aggressive tumors of the brain or spine) remain dismal, with 5-year overall survival tragically <10%, despite intensive surgery, radiation, and/or chemotherapy. Diffuse intrinsic pontine glioma (DIPG) is a type of HGG in the brainstem that cannot be operated on, does not respond to standard chemotherapy, and has an average survival of less than 12 months. There is therefore a critical need to develop effective, well-tolerated therapies for children, adolescents, and young adults with HGGs. Recent scientific discoveries have provided valuable insight into the genomics of these aggressive diseases and identified genetic changes which can serve as future targets for therapy. Research has helped develop less-toxic medicines, usually oral drugs, that can directly target specific genetic alterations present in the tumor to slow or stop its growth and spare healthy organs. We propose an innovative multi-arm clinical trial offering a precision medicine approach to treat children, adolescents, and young adults newly diagnosed with high-grade gliomas, including DIPG. Detailed genetic sequencing using advanced technology will be performed on tumor tissue from all patients upfront, with return of results within 3 weeks. Patients will then be assigned to one of several unique molecularly targeted treatment arms based on (and directly targeting) the genetic alterations identified in their tumor. There are also treatment arms available for patients whose tumors do not have the specific genetic alterations evaluated to offer them new therapies that have shown potential for success in preclinical and clinical models of pediatric HGGs. Therefore, all HGG and DIPG patients who enroll on this trial will be offered novel therapy, guided by the distinct genetic profile of their tumors, and based on evidence from emerging scientific research. Furthermore, in addition to studying the genetic alterations present in tumor tissue prior to treatment, we will collect blood samples as well as cerebrospinal fluid (CSF) and/or future tumor tissue (if a second surgery is performed) throughout the study. Genomic and immune profiling analyses will be performed on these specimens over time to identify biomarkers (liquid biopsy tools) that can predict early response or recurrence to treatment and improve the understanding of why some tumors become resistant to therapy. Fiscal Year 2022 Peer Reviewed Cancer Research Program (FY22 PRCRP) Topic Area: This new molecularly guided clinical trial offers targeted therapies to children, adolescents, and young adults with difficult-to-treat brain cancer (HGGs, including DIPG). Through this research, we aim to improve outcomes and identify biomarkers predictive of response, recurrence, and resistance to molecularly-targeted treatments in high-risk pediatric brain tumors. FY22 PRCRP Military Health Focus Area: The diagnosis of cancer in a military member, Veteran, or their children represents a substantial burden, both emotionally and financially, that directly affects mission readiness. Pediatric HGGs, including DIPG, are especially devastating given their extremely poor prognosis, lack of effective treatments, and associated debilitating neurologic deficits, requiring family members to serve as full-time caregivers. By evaluating several molecularly targeted therapies for pediatric HGGs, our research aims to improve outcomes, increase availability of effective treatments, and decrease therapy side effects for military families battling brain/spine tumors. Lessons learned from these studies will not only be directly applicable to HGGs in children, but likely to other aggressive tumor types across ages (the genetic alterations being targeted are seen in many cancers). Therefore, results from this t
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310770
Entities
People
- Maryam Fouladi
Organizations
- United States Army