Prospective Assessment of Predictive/prognostic molecular biomarkers in the SIOP-LGG 201X adaptive phase III clinical trial

Award: $428,000 over 2 years (2019 – 2021)
Principal Investigators: Dr. David Jones and Dr. Stefan Pfister, Heidelberg German Cancer Institute

The principle aim of the trial is to identify the optimum treatment regimen with respect to efficacy, improvement of visual and neurological function, reduction of neurotoxicity as well as treatment duration using a randomized comparison of vinblastine (VBL) versus vincristine (VCR) in a carboplatin-based chemotherapy regimen, also randomizing 18 versus 12 months treatment duration. An additional novel point of the planned trial is the adaptive design and interim analyses (from year 3 onwards), which will allow for the timely investigation of novel targeted agents, once a chemotherapy standard of care ‘winner’ has been established (VCR vs VBL, 12 vs 18 months). The overarching aim of this proposed funding application will be to provide a comprehensive molecular characterization of all patient tumor samples collected during the course of the SIOP‐LGG 201X trial as well as an associated registry study for all newly-diagnosed pediatric LGG (see Appendix B). This is a pan-European, population-based study, with an expected recruitment of >90% of all newly diagnosed LGGs in the 19 participating countries. Since LGG patients often suffer from significant damage to important functional structures of the brain, particularly for tumors located in central midline structures, the current trial for the first time includes assessment of acute and long-term morbidities to visual and neurological function as a primary outcome measure. We will therefore have access to tumor and germline material from a very large, uniformly-treated cohort with very detailed and standardized clinical annotation and careful follow-up.