Rechallenge therapy for BRAF-positive anaplastic thyroid cancer after previous treatment failure

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

This study is testing if giving BRAF-positive anaplastic thyroid cancer patients their previous targeted therapy again can help them after their cancer has progressed on other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Saint Petersburg State University, Russia (Academic / other)
• Drugs / interventions: trametinib, chemotherapy
• Locations: 1 site (Saint Petersburg)
• Trial ID: NCT06362694 on ClinicalTrials.gov

What this trial studies

This pilot phase 2 study evaluates the effectiveness and safety of rechallenging patients with BRAF-positive anaplastic thyroid cancer using targeted therapy after they have experienced progression on anti-BRAF therapy. Eligible patients, who previously responded to treatment with dabrafenib and trametinib, will receive these medications again following progression during anti-BRAF therapy and at least one line of chemotherapy. The study aims to assess the outcomes based on predefined primary and secondary endpoints, monitoring clinical and laboratory parameters throughout the process.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with immunohistochemically verified BRAF-positive anaplastic thyroid cancer who have previously responded to dabrafenib and trametinib but have since experienced disease progression.

Not a fit: Patients who have primary resistance to anti-BRAF therapy or those who cannot tolerate the study drugs will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for patients with BRAF-positive anaplastic thyroid cancer who have limited options after progression on standard therapies.

How similar studies have performed: While the rechallenge concept is being explored, this specific approach in BRAF-positive anaplastic thyroid cancer is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria:

* 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.

Where this trial is running

Saint Petersburg

• Saint Petersburg State University Hospital — Saint Petersburg, Russia (Recruiting)

Study contacts

• Study coordinator: Ilya Sleptsov, MD

Conditions Anaplastic Thyroid Cancer; anaplastic thyroid cancer; rechallenge; dabrafenib; trametinib; targeted therapy