TarGeT: TARGETED PEDIATRIC HIGH-GRADE GLIOMA THERAPY Molecularly-Guided Phase 2 Umbrella Trial for Children, Adolescents, and Young Adults Newly Diagnosed with High-Grade Glioma (HGG), including Diffuse Intrinsic Pontine Glioma (DIPG) SCREENING PROTOCOL
CONNECT TarGeT SCR
What is the goal of the study?
High-Grade Gliomas (HGGs), including Diffuse Midline Glioma (DMG) and Diffuse Intrinsic Pontine Glioma (DIPG), are a leading cause of cancer-related death in children, adolescents, and young adults. Despite intensive multimodal therapy, prognosis for pediatric and young adult patients diagnosed with this aggressive brain and/or spine tumor remains dismal, with 5-year overall survival (OS) <10%. motivated by this critical need to develop novel effective and well-tolerated therapies for pediatric hggs and guided by recent discoveries which have improved the understanding of their genomic landscape the proposed study outlines an innovative phase ii trial that is molecularly-guided. the target targeted pediatric high-grade glioma therapy trial will employ central comprehensive molecular characterization of tumors using a multi-omic approach including whole exome or whole genome sequencing wes wgs fusion panels and or rna sequencing and dna methylation microarray. these analyses will be performed across international connect genomics cores clinical molecular testing laboratories with rapid return of clinically validated results to guide assignment to one of several biologically-guided treatment arms. in addition longitudinal collection of peripheral blood cerebrospinal fluid csf and or tumor tissue will allow correlative genomic and immune profiling analyses. when integrated with robust clinical outcome data advanced neuro-imaging and patient-reported outcomes these approaches will facilitate identification of multimodal biomarkers predictive of response recurrence and resistance to these targeted agents. the target study consists of the present screening protocol to assess eligibility of patients to enroll on treatment subprotocols each offering treatments that target specific genomic alterations and molecular pathways identified in individual patients tumors as shown in the study schema below figure 1. the treatment subprotocols were designed based on a known prevalence of respective molecular and biologic targets in pediatric hgg and dipg b previous pediatric phase i studies with recommended phase ii dosing rp2d or adequate safety feasibility data c availability of relevant agents provided by collaborating industry partners and d prioritization of combination therapy based on preclinical and clinical data suggesting synergy in these diseases. all patients will receive upfront radiotherapy followed by adjuvant targeted therapy some targeted agents will be given concurrently with radiotherapy. patients must have sufficient tumor tissue sample available from diagnostic biopsy or resection for molecular characterization and therapeutic arm assignment.>
Who can participate in the study?
Please contact the study team listed below to learn more.