Combination therapy Dabrafenib and Trametinib in patients with HGG and newly diagnosed low grade glioma (LGG)

"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) relapsed or refractory High Grade Glioma (HGG)"

The aim of the study is to find out whether treatment with dabrafenib and trametinib is a safe and effective treatment option for children and adolescents with HGG with a specific mutation in the BRAF gene (BRAFV600) and unresponsive or resistant to standard therapy.

Dabrafenib and trametinib are already approved as a combination therapy for the treatment of a specific type of skin cancer in adults.

The BRAF V600 mutation modifies the function of the protein kinase BRAF, which controls the growth and proliferation of cells. Dabrafenib is a drug from the group of protein kinase inhibitors and inhibits the function of the protein BRAF. Trametinib enhances the effects of dabrafenib. In the tumor, a BRAFV600 mutation must be detected by molecular diagnostics. Dabrafenib is taken twice daily, trametinib once daily in the form of capsules. For younger patients or patients with dysphagia, a suspension is offered.

In the LGG cohort, patients are randomized, i.e. they receive either combination therapy with dabrafenib and trametinib or standard therapy (vincristine and carboplatin). As the disease progresses under standard therapy, patients may switch to treatment with combination therapy.

The inclusion of patients in Heidelberg has been possible since 1 January 2018.

  • Age ≥ 6 and  < 18 years at the time of consent
  • HGG cohort: Recurrent, refractory or progressive disease after standard therapy for the disease
  • LGG cohort: Patients with non-resectable tumor in need of treatment after initial diagnosis
  • At least one measurable lesion
  • Molecular proof of a BRAF V600-mutation positive tumor
  • Score of 50% on the Karnofsky/Lansky performance status scale
  • Adequate bone marrow, kidney, liver and heart function

For more information, see the Study Registry: The study is registered with the U.S. National Institutes of Health (ClinicalTrials.gov).
See NCT02684058  

EudraCT-number: 2015-004015-20 (see EU clinical trial register)