Clinical trial · Interventional
Study of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Pediatric Patients With BRAF V600 Mutation Positive LGG or Relapsed or Refractory HGG Tumors
Phase II Open-label Global Study to Evaluate the Effect of Dabrafenib in Combination With Trametinib in Children and Adolescent Patients With BRAF V600 Mutation Positive Low Grade Glioma (LGG) or Relapsed or Refractory High Grade Glioma (HGG)
NCT02684058CI-TRIAL-00072209completedPhase 2Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
The purpose of this study was to investigate the activity of dabrafenib in combination with trametinib in children and adolescent patients with BRAF V600 mutation positive low grade glioma (LGG) or relapsed or refractory high grade glioma (HGG)
Conditions
Conditions (22)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Anaplastic Astrocytoma | Anaplastic Astrocytoma | CURATED_BROADER | 0.80 |
| Anaplastic Ganglioglioma | Anaplastic Ganglioglioma | ONTOLOGY_EXACT | 0.98 |
| Anaplastic Oligodendroglioma | Anaplastic Oligodendroglioma | CURATED_BROADER | 0.80 |
| Anaplastic Pleomorphic Xanthoastrocytoma | Anaplastic Pleomorphic Xanthoastrocytoma | ONTOLOGY_EXACT | 0.98 |
| Angiocentric Glioma | Angiocentric Glioma | ONTOLOGY_EXACT | 0.98 |
| Astrocytoma | Astrocytoma | CURATED_BROADER | 0.80 |
| Central Neurocytoma | Central Neurocytoma | ONTOLOGY_EXACT | 0.98 |
| Cerebellar Iponeurocytoma | — | UNRESOLVED | — |
| Chordoid Glioma of Third Ventricle | Chordoid Glioma |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Carboplatin | Drug | Carboplatin | ALIAS |
| Dabrafenib | Drug | Dabrafenib | ALIAS |
| trametinib | Drug | Trametinib | ALIAS |
| Vincristine | Drug | Vincristine | ALIAS |
Design
Arms and outcomes
Arms (3)
- type
- EXPERIMENTAL
- label
- LGG cohort: dabrafenib and trametinib
- description
- Participants in the LGG cohort randomized to receive dabrafenib (orally, twice daily and dosed based on weight and age) in combination with trametinib (orally, once daily in combination with the first daily dose of dabrafenib and was dosed based on weight)
- interventionNames
- Drug: Dabrafenib
- Drug: trametinib
- type
- ACTIVE_COMPARATOR
- label
- LGG cohort: carboplatin and vincristine
- description
- Participants in the LGG cohort randomized to receive active comparator chemotherapy (carboplatin and vincristine). Participants received one course of induction (10 weeks of chemotherapy with 2 weeks of rest), followed by 8 cycles of maintenance chemotherapy.
- interventionNames
- Drug: Carboplatin
- Drug: Vincristine
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 12 Months
- Maximum age
- 17 Years
Show eligibility criteria text
Key Inclusion Criteria: * Diagnosis of BRAF V600 mutant High Grade glioma that had relapsed, progressed or failed to respond to frontline therapy * Diagnosis of BRAF V600 mutant Low Grade glioma with progressive disease following surgical excision, or non-surgical candidates with necessity to begin first systemic treatment because of a risk of neurological impairment with progression. * Confirmed measurable disease Key Exclusion Criteria: * Previous treatment with dabrafenib, trametinib, other RAF inhibitor, other MEK or ERK inhibitor * HGG patient: Cancer treatment within the past 3 weeks. LGG patient: Any systemic therapy or radiotherapy prior to enrollment * LGG patients: history of allergic reaction or contraindications to the use of carboplatin or vincristine * Stem cell transplant within the past 3 months * History of heart disease * Pregnant or lactating females
References
Publications (5)
- DERIVEDGascon B, Gauvreau C, Yang A, Bennett J, Nobre L, Tabori U, Hawkins C, Tsang D, Pechlivanoglou P, Denburg A. Cost-Effectiveness of Dabrafenib Plus Trametinib Versus Standard Chemotherapy in BRAFV600E-Mutant Pediatric Low-Grade Glioma. JCO Oncol Pract. 2026 Feb 25:OP2501263. doi: 10.1200/OP-25-01263. Online ahead of print. PMID 41740060
- DERIVEDBouffet E, Hansford JR, Garre ML, Hara J, Plant-Fox A, Aerts I, Locatelli F, van der Lugt J, Papusha L, Sahm F, Tabori U, Cohen KJ, Packer RJ, Witt O, Sandalic L, Bento Pereira da Silva A, Russo M, Hargrave DR. Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations. N Engl J Med. 2023 Sep 21;389(12):1108-1120. doi: 10.1056/NEJMoa2303815. PMID 37733309
- DERIVEDHargrave DR, Terashima K, Hara J, Kordes UR, Upadhyaya SA, Sahm F, Bouffet E, Packer RJ, Witt O, Sandalic L, Kieloch A, Russo M, Cohen KJ; Investigators involved in the high-grade glioma cohort. Phase II Trial of Dabrafenib Plus Trametinib in Relapsed/Refractory BRAF V600-Mutant Pediatric High-Grade Glioma. J Clin Oncol. 2023 Nov 20;41(33):5174-5183. doi: 10.1200/JCO.23.00558. Epub 2023 Aug 29. PMID 37643378
- DERIVEDBarbato MI, Nashed J, Bradford D, Ren Y, Khasar S, Miller CP, Zolnik BS, Zhao H, Li Y, Bi Y, Shord SS, Amatya AK, Mishra-Kalyani PS, Scepura B, Al-Matari RA, Pazdur R, Kluetz PG, Donoghue M, Singh H, Drezner N. FDA Approval Summary: Dabrafenib in Combination with Trametinib for BRAFV600E Mutation-Positive Low-Grade Glioma. Clin Cancer Res. 2024 Jan 17;30(2):263-268. doi: 10.1158/1078-0432.CCR-23-1503. PMID 37610803
- DERIVEDShahid S, Kushner BH, Modak S, Basu EM, Rubin EM, Gundem G, Papaemmanuil E, Roberts SS. Association of BRAF V600E mutations with vasoactive intestinal peptide syndrome in MYCN-amplified neuroblastoma. Pediatr Blood Cancer. 2021 Oct;68(10):e29265. doi: 10.1002/pbc.29265. Epub 2021 Jul 31. PMID 34331515