NCT04940052

Study of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Previously Treated Patients With Metastatic, Radio-active Iodine Refractory BRAF V600E Mutation Positive Differentiated Thyroid Cancer

A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of Dabrafenib Plus Trametinib in Previously Treated Patients With Locally Advanced or Metastatic, Radio-active Iodine Refractory BRAFV600E Mutation-positive Differentiated Thyroid Cancer (DTC)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 153 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to assess the efficacy and safety of dabrafenib in combination with trametinib for treating adult patients with locally advanced or metastatic Differentiated Thyroid Cancer (DTC) harboring the BRAFV600E mutation, who are refractory to radioactive iodine (RAI) therapy and have experienced disease progression following one or two prior VEGFR-targeted treatments.

Detailed description

This is a global, multicenter, randomized, double-blind, placebo-controlled phase III study to evaluate the efficacy and safety of dabrafenib plus trametinib in adult patients with locally advanced or metastatic BRAFV600E mutation-positive, differentiated thyroid carcinoma who are refractory to radioactive iodine and have progressed following prior VEGFR targeted therapy. The scientific objective guiding the primary estimand is based on the Progression Free Survival (PFS) as per BIRC assessment using RECIST 1.1 criteria. Patients randomized in the placebo arm for whom disease progression as per RECIST 1.1 is confirmed by Blinded Independent Review Committee (BIRC) and who meet the eligibility criteria outlined in the study protocol will be given the option to crossover to the open-label dabrafenib plus trametinib treatment.

Conditions

• Differentiated Thyroid Cancer (DTC)

Interventions

Type	Name	Description
DRUG	Dabrafenib	Dabrafenib 150 mg capsule administered orally twice a day (BID)
DRUG	Trametinib	Trametinib 2 mg tablet administered once a day (QD)
DRUG	Trametinib Placebo	matching placebo tablet for Trametinib 2 mg will be administered orally once a day (QD)
DRUG	Dabrafenib placebo	matching placebo capsule for Dabrafenib 150 mg will be administered orally twice a day (BID)

Timeline

• Start date: 2021-11-15
• Primary completion: 2025-01-22
• Completion: 2027-06-04
• First posted: 2021-06-25
• Last updated: 2025-12-02

Locations

41 sites across 11 countries: United States, Argentina, Brazil, Canada, China, India, Malaysia, South Korea, Taiwan, Turkey (Türkiye), Vietnam

Regulatory

• FDA-regulated drug study