This pilot phase 2 study evaluates the effectiveness and safety of the Rechallenge concept in patients with BRAF-positive anaplastic thyroid cancer after progression on anti-BRAF therapy. Patients with BRAF-positive anaplastic thyroid cancer who were previously treated with dabrafenib and trametinib (with a clinical or objective response at the start of treatment) and later with tumor progression during anti-BRAF therapy and subsequent lines of chemotherapy are scheduled to undergo targeted therapy (repeated administration of dabrafenib and trametinib in standard doses) and evaluate the outcomes according to the primary and secondary endpoints.
immunohistochemically verified anaplastic thyroid cancer;
presence of a mutation in the BRAF V600 gene;
documented progression during targeted therapy with dabrafenib + trametinib;
documented progression during at least one line of chemotherapy (use of taxane-containing chemotherapy is mandatory);
primary resistance (absence of initial clinical and radiological response to therapy with dabrafenib and trametinib (response criteria - primary objective response according to RECIST 1.1 criteria and duration of response of at least 3 months);
absence of taxane-containing chemotherapy as second or third line;
contraindication to taking any of the study drugs (including severe toxicity that occurred during a previous dose, which led to discontinuation of treatment);
patients with unsatisfactory functional status (ECOG 3-4);
Single group
Dabrafenib + Trametinib
DrugDabrafenib is an inhibitor of some mutated forms of BRAF kinases. Trametinib is a reversible inhibitor of mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2 activation and of MEK1 and MEK2 kinase activity. Dabrafenib and trametinib target two different kinases in the RAS/RAF/MEK/ERK pathway. Use of dabrafenib 623 and trametinib in combination resulted in greater growth inhibition of BRAF V600 mutation-positive tumors.
Objective response rate
The proportion of participants with a partial or complete response to the therapy. It is determined according to the RECIST criteria.
Progression-Free Survival
The time from the date of initiation of treatment to the radiological progression or death of the patient for any reason.
Safety and Tolerability assessment (Incidence of Treatment-Emergent Adverse Events)
Safety assessment will be assessed on the basis of adverse events (according to CTCAE 5.0)
Overall survival
The time from the start date of treatment to the death of the patient for any reason.
The assessment of conversion to resectability
The proportion of participants with an initially unresectable or potentially resectable tumor who have moved to a resectable during treatment.
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