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

NCT06362694 | Recruiting Phase 2 DMC

• 1 other identifier: 34
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Anaplastic Thyroid Cancer

Keywords

anaplastic thyroid cancer; rechallenge; dabrafenib; trametinib; targeted therapy

Outcome Measures

Primary Outcomes (3)

• Objective response rate

  The proportion of participants with a partial or complete response to the therapy. It is determined according to the RECIST criteria.

  10 days, then each month from date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months

• Progression-Free Survival

  The time from the date of initiation of treatment to the radiological progression or death of the patient for any reason.

  6-month, 1-year, 2-year

• 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)

  Each visit (every 21 days) assessed up to 48 months

Secondary Outcomes (2)

• Overall survival

  6-month, 1-year, 2-year

• The assessment of conversion to resectability

  Each month from date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first , assessed up to 48 months

Study Arms (1)

Intervention group

EXPERIMENTAL

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 with the transition to at least one line of chemotherapy (treatment with taxane-containing regimens is mandatory) followed by progression on it.

Drug: Dabrafenib + Trametinib

Interventions

Dabrafenib + Trametinib DRUG

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.

Intervention group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Saint Petersburg State University, Russia: lead

Study Sites (1)

Saint Petersburg State University Hospital

Saint Petersburg, 190020, Russia

RECRUITING

MeSH Terms

Conditions

Thyroid Carcinoma, Anaplastic

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Central Study Contacts

Ilya Sleptsov, MD

CONTACT

+7(921)951-70-88; newsurgery@yandex.ru

Ernest Dzhelialov

CONTACT

+7(911)134-50-44; ernest.dzhelialov@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Oncologist

Study Record Dates

• First Submitted: March 28, 2024
• First Posted: April 12, 2024
• Study Start: March 25, 2024
• Primary Completion: March 25, 2026
• Study Completion (Estimated): June 25, 2026
• Last Updated: April 12, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

RU (1)