NCT06475989

Study of Targeted Therapy vs. Chemotherapy in Patients With Thyroid Cancer

A Randomized Phase III Study of BRAF-Targeted Therapy vs Cabozantinib in RAI-Refractory Differentiated Thyroid Cancer With BRAF V600Em

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 264 (estimated)
• Sponsor: ECOG-ACRIN Cancer Research Group · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase III trial compares the effect of cabozantinib versus combination dabrafenib and trametinib for the treatment of patients with differentiated thyroid cancer that does not respond to treatment (refractory) and which expresses a BRAF V600E mutation. Cabozantinib is in a class of medications called receptor tyrosine kinase inhibitors. It binds to and blocks the action of several enzymes which are often over-expressed in a variety of tumor cell types. This may help stop or slow the growth of tumor cells and blood vessels the tumor needs to survive. Dabrafenib is an enzyme inhibitor that binds to and inhibits the activity of a protein called B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. Trametinib is also an enzyme inhibitor. It binds to and inhibits the activity of proteins called MEK 1 and 2, which play a key role in activating pathways that regulate cell growth. This may inhibit the growth of tumor cells mediated by these pathways. The usual approach for patients with thyroid cancer is targeted therapy with dabrafenib and trametinib. This trial may help researchers decide which treatment option (cabozantinib alone or dabrafenib in combination with trametinib) is safer and/or more effective in treating patients with refractory BRAF V600E-mutated differentiated thyroid cancer.

Detailed description

PRIMARY OBJECTIVE: I. To compare progression-free survival (PFS) in patients with BRAF V600Em differentiated thyroid cancer who progressed on frontline multikinase inhibitor treated with dabrafenib/trametinib or cabozantinib. SECONDARY OBJECTIVES: I. To compare the objective response rate in patients with BRAF V600Em differentiated thyroid cancer that progressed on frontline multikinase inhibitor treated with dabrafenib/trametinib or cabozantinib. II. To compare the duration of response in patients with BRAF V600Em differentiated thyroid cancer that progressed on frontline multikinase inhibitor treated with dabrafenib/trametinib or cabozantinib. III. To compare the overall survival in patients with BRAF V600Em differentiated thyroid cancer that progressed on frontline multikinase inhibitor treated with dabrafenib/trametinib or cabozantinib. IV. To compare the PFS2 in patients with BRAF V600Em differentiated thyroid cancer that progressed on frontline multikinase inhibitor treated with dabrafenib/trametinib or cabozantinib. V. To compare the safety/tolerability in patients with BRAF V600Em differentiated thyroid cancer that progressed on frontline multikinase inhibitor treated with dabrafenib/trametinib or cabozantinib. QUALITY OF LIFE OBJECTIVE: I. To assess patient tolerability of treatment using the Functional Assessment Cancer Therapy General (FACT G)P5 and general quality of life using the FACT-G7. OUTLINE: Patients are randomized to 1 of 2 arms. Patients may crossover to other treatment arm at the time of progression. ARM A: Patients receive dabrafenib orally (PO) twice per day (BID) and trametinib PO once per day (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, blood sample collection and may undergo magnetic resonance imaging (MRI) throughout the study. ARM B: Patients receive cabozantinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, blood sample collection and may undergo MRI throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months thereafter up to 5 years.

Conditions

• Refractory Differentiated Thyroid Gland Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
DRUG	Cabozantinib	Given PO
PROCEDURE	Computed Tomography	Undergo CT scan
DRUG	Dabrafenib	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
OTHER	Questionnaire Administration	Ancillary study
DRUG	Trametinib	Given PO

Timeline

• Start date: 2024-08-22
• Primary completion: 2030-09-30
• Completion: 2030-09-30
• First posted: 2024-06-26
• Last updated: 2026-03-23

Locations

112 sites across 1 country: United States

Regulatory

• FDA-regulated drug study