{"entity":{"id":"tadpole","kind":"trial","name":"TADPOLE (CDRB436G2201)","aka":[],"tldr":"The first randomised trial to show that a targeted drug pair beats chemotherapy in children with a brain tumour. Children whose low-grade glioma carries a BRAF V600 mutation had far more tumour shrinkage and a much longer time before progression on dabrafenib plus trametinib than on standard carboplatin and vincristine.","summary":"Phase 2 randomised trial (Bouffet et al., NEJM 2023). 110 patients randomised (73 to dabrafenib plus trametinib, 37 to carboplatin plus vincristine). At a median follow-up of 18.9 months the independently assessed overall response rate was 47% versus 11% (risk ratio 4.31; 95% CI 1.7 to 11.2), clinical benefit 86% versus 46%, and median progression-free survival 20.1 versus 7.4 months (HR 0.31; 95% CI 0.17 to 0.55). Grade 3 or higher adverse events were less frequent with the targeted pair (47% versus 94%). Basis of the FDA approval of dabrafenib plus trametinib for paediatric BRAF V600E LGG in March 2023, with new liquid and dispersible formulations for young children. A separate cohort in relapsed BRAF V600 high-grade glioma also responded.","status":"positive","asOf":"2026-09-10","links":[{"label":"ClinicalTrials.gov NCT02684058","url":"https://clinicaltrials.gov/study/NCT02684058"},{"label":"Bouffet et al., NEJM 2023","url":"https://doi.org/10.1056/NEJMoa2303815"}],"tags":["nci-coverage","paediatric","cns"],"related":[],"cancers":["paediatric-low-grade-glioma"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["braf"],"drugs":["dabrafenib-trametinib","carboplatin","vincristine"],"companies":["novartis"],"institutions":[],"pathways":["ras-mapk"],"terms":["braf-v600-mutation","race-for-children-act"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-bouffet-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02684058","phase":"2","setting":"Newly diagnosed BRAF V600-mutant paediatric low-grade glioma needing systemic therapy: dabrafenib + trametinib vs carboplatin + vincristine (2:1 randomisation)","sponsor":"Novartis","result":"ORR 47% vs 11%; median PFS 20.1 vs 7.4 months, HR 0.31.","started":"2017-12-28","startedType":"actual","yearReported":2023,"enrolled":110,"enrolledBasis":"randomised","enrolledNote":"ClinicalTrials.gov lists 151 participants (actual) across the study's cohorts; the NEJM 2023 low-grade glioma analysis randomised 110 patients (73 dabrafenib plus trametinib, 37 chemotherapy).","outcomes":[{"endpoint":"Overall response rate (independent review, RANO)","primary":true,"unit":"%","arms":[{"name":"Dabrafenib + trametinib","n":73,"value":47},{"name":"Carboplatin + vincristine","n":37,"value":11}],"p":"<0.001","source":"https://doi.org/10.1056/NEJMoa2303815"},{"endpoint":"Progression-free survival","unit":"months","arms":[{"name":"Dabrafenib + trametinib","n":73,"value":20.1},{"name":"Carboplatin + vincristine","n":37,"value":7.4}],"hr":0.31,"ci":[0.17,0.55],"p":"<0.001","source":"https://doi.org/10.1056/NEJMoa2303815"}],"replication":"Consistent with earlier single-arm paediatric dabrafenib and trametinib studies; the only randomised comparison so far. FIREFLY-1 addressed the BRAF-fusion population that this trial excluded."},"route":"/trials/tadpole/","neighbours":{"cancer":[{"id":"paediatric-low-grade-glioma","kind":"cancer","name":"Paediatric low-grade glioma","route":"/cancers/paediatric-low-grade-glioma/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + trametinib","route":"/drugs/dabrafenib-trametinib/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"braf-v600-mutation","kind":"term","name":"BRAF V600E mutation","route":"/terms/braf-v600-mutation/"},{"id":"race-for-children-act","kind":"term","name":"RACE for Children Act","route":"/terms/race-for-children-act/"}],"paper":[{"id":"paper-bouffet-n-engl-j-med","kind":"paper","name":"Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations","route":"/key-papers/paper-bouffet-n-engl-j-med/"}],"roadmap":[{"id":"paediatric-oncology-roadmap","kind":"roadmap","name":"Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first","route":"/roadmaps/paediatric-oncology-roadmap/"}]}}