RecruitingPhase 2NCT06362694

Study of the Rechallenge Concept in Patients With BRAF-positive Anaplastic Thyroid Cancer After Progression on Anti-BRAF Therapy

Sponsor

Saint Petersburg State University, Russia

Enrollment

10 participants

Start Date

Mar 25, 2024

Study Type

INTERVENTIONAL

Conditions

Anaplastic Thyroid Cancer

Summary

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria8

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);
age ≥ 18 years;
ECOG performance status 0-2;
adequate function of internal organs and bone marrow;
ability to give written informed consent.

Exclusion Criteria5

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);
pregnancy and breastfeeding.

Interventions

DRUGDabrafenib + Trametinib

Dabrafenib 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.