Author: Julia Dobke, erstellt am: 2018/09/12, Last modification: 2019/03/13

Dabrafenib/Trametinib 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 positive Low Grade Glioma (LGG) or relapsed or refractory High Grade Glioma (HGG)
Disease Low Grade Glioma (LGG, High grade glioma (HGG)
Type Multicenter, open-label phase II
Problem / Objectives

Primary objective:
-Evaluate the anti-tumor activity of dabrafenib in combination with trametinib, as measured by overall response rate (ORR) to the combination therapy by RANO criteria.
Secondary objectives:
-Evaluate ORR, duration and time of response (DOR and TTR),
-Evaluate progression free survival (PFS) and Overall survival (OS)
-Evaluate safety profile of dabrafenib in combination with trametinib
-Pharmacokinetics of dabrafenib, its metabolites and trametinib

Inclusion Criteria
  • Male or female between ≥ 6 and <18 years of age
  • For HGG-cohort only: Relapsed, progressed, or failed to respond to frontline therapy. Frontline therapy is presumed to be optimal surgical approach (biopsy or resection) with radiation and/or chemotherapyRelapsed, progressed, or failed to respond to frontline therapy
  • For LGG cohort only: Patients whose tumor is unresectable and who require treatment
  • Histologically confirmed diagnosis of High Grade Glioma (Grade III or IV glioma as defined by WHO histological classification system) or locally confirmed histologic diagnosis of Low Grade Glioma (Grade I or II).
  • Locally determined and centrally confirmed measurable disease with minimal biperpendicular diameter that must be at least twice the imaging slice thickness
  • BRAF V600 mutation-positive tumor as locally determined using molecular methods
  • Karnofsky / Lansky ≥ 50 %
Exclusion Criteria
  • Malignancy OTHER than BRAF V600 mutant HGG or LGG
  • Previous treatment with dabrafenib or another RAF inhibitor, trametinib or another MEK inhibitor, or ERK inhibitor
Recruitment 40
Status recruiting
EudraCT 2015-004015-20
Entry Study Register
Principal Investigator Prof. Dr. med. Olaf Witt

PI Germany

Prof. Dr. med. Olaf Witt
Universität Heidelberg, Hopp-Kindertumorzentrum am NCT Heidelberg (KiTZ)
Klinik für Kinderheilkunde III Onkologie, Hämatologie, Immunologie
Im Neuenheimer Feld 430
69120 Heidelberg
Telefon +49 (0) 6221 42 3570 or +49 (0)6221 56 38786

Participants Heidelberg, Augsburg (geplant ab Oktober 2018), Berlin, Essen, Göttingen, Hamburg, Köln
Sponsoring Novartis