NCT04739566: ANAPLAST-NEO

Dabrafenib and Trametinib Combination as a Neoadjuvant Strategy in BRAF-positive Anaplastic Thyroid Cancer

Withdrawn Phase 2 Last updated 25 March 2024

What this trial tests

Phase 2 trial testing Dabrafenib in Thyroid Gland Anaplastic Carcinoma. Withdrawn.

Timeline

22 January 2021

Primary endpoint
22 December 2023

22 December 2023

Quick facts

Lead sponsor	Saint Petersburg State University, Russia
Phase	Phase 2
Status	Withdrawn
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Start date	22 January 2021
Primary completion	22 December 2023
Estimated completion	22 December 2023
Sites	1 location across Russia

Drugs / interventions tested

• Dabrafenib (dabrafenib) — full drug profile →
• Trametinib (trametinib) — full drug profile →

Conditions studied

• Thyroid Gland Anaplastic Carcinoma — all drugs for Thyroid Gland Anaplastic Carcinoma →

Sponsor

Saint Petersburg State University, Russia

Who can join

18 and older, any sex, with Thyroid Gland Anaplastic Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Anaplastic Thyroid Carcinoma: An Update.
   Jannin A, Escande A, Al Ghuzlan A, Blanchard P, et al · · 2022 · cited 110× · PMID 35205809 · DOI 10.3390/cancers14041061
2. Novel Inhibitor-Based Therapies for Thyroid Cancer-An Update.
   Ratajczak M, Gaweł D, Godlewska M. · · 2021 · cited 37× · PMID 34769260 · DOI 10.3390/ijms222111829
3. Onco-immunomodulatory properties of pharmacological interference with RAS-RAF-MEK-ERK pathway hyperactivation.
   Avery TY, Köhler N, Zeiser R, Brummer T, et al · · 2022 · cited 31× · PMID 35965494 · DOI 10.3389/fonc.2022.931774
4. Molecular features of aggressive thyroid cancer.
   Elia G, Patrizio A, Ragusa F, Paparo SR, et al · · 2022 · cited 26× · PMID 36605433 · DOI 10.3389/fonc.2022.1099280
5. The Role of the Kinase Inhibitors in Thyroid Cancers.
   Cuomo F, Giani C, Cobellis G. · · 2022 · cited 18× · PMID 35631627 · DOI 10.3390/pharmaceutics14051040
6. Neoadjuvant therapy to improve resectability of advanced thyroid cancer: A real-world experience.
   Russell M, Gild ML, Wirth LJ, Robinson B, et al · · 2024 · cited 17× · PMID 38488238 · DOI 10.1002/hed.27735
7. Advances in Biomarker-Driven Targeted Therapies in Thyroid Cancer.
   Mishra P, Laha D, Grant R, Nilubol N. · · 2021 · cited 9× · PMID 34944814 · DOI 10.3390/cancers13246194
8. Anaplastic thyroid cancer: genome-based search for new targeted therapy options.
   Hescheler DA, Hartmann MJM, Riemann B, Michel M, et al · · 2022 · cited 7× · PMID 35275096 · DOI 10.1530/ec-21-0624