Dabrafenib and Trametinib Combination as a Neoadjuvant Strategy in BRAF-positive Anaplastic Thyroid Cancer
Status:
Recruiting
Trial end date:
2026-01-22
Target enrollment:
Participant gender:
Summary
The aim of the study was to evaluate the effectiveness of combination therapy with dabrafenib
and trametinib (anti-BRAF and anti-MEK inhibitors) in the neoadjuvant treatment of
BRAF-positive anaplastic thyroid cancer. The prognosis in patients with ATC is poor due to
the rapid and invasive tumor growth and the rapid development of metastases.
Dabrafenib is an antineoplastic agent, a selective RAF kinase inhibitor that competes with
ATP. Oncogenic substitutions of the amino acid valine at position 600 (V600) BRAF lead to
constitutive activation of the RAS / RAF / MEK / ERK pathway and stimulation of tumor cell
growth.
Trametinib is a reversible, highly selective, allosteric inhibitor of the activation of
mitogen-activated, extracellular signal-regulated kinases 1 (MEK1) and 2 (MEK2).
Dabrafenib and trametinib inhibit two kinases in the signaling pathway, BRAF, and MEK. The
combination of the two drugs provides effective inhibition of proliferative signal
conduction.
The investigators hypothesize that the combination treatment with these two drugs -
dabrafenib and trametinib - can improve the response rate in the neoadjuvant mode in ATC
without significant regimen-limiting toxicity and with better follow-up locoregional control.