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)
1 other identifier
interventional
153
11 countries
41
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Nov 2021
Longer than P75 for phase_3
41 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 22, 2021
CompletedFirst Posted
Study publicly available on registry
June 25, 2021
CompletedStudy Start
First participant enrolled
November 15, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 22, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
June 4, 2027
ExpectedDecember 2, 2025
November 1, 2025
3.2 years
June 22, 2021
November 24, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
Progression Free Survival (PFS) was defined as the time from the date of randomization to the date of the first documented progression according to RECIST 1.1 based on Blinded Independent Review Committee (BIRC) assessment, or death due to any cause.
From randomization to first documented progression or deaths, whichever comes first, assessed up to approximately 2 years
Secondary Outcomes (5)
Overall Response Rate (ORR)
From randomization up to approximately 2 years
Overall Survival (OS)
From randomization to death assessed up to approximately 5 years
Duration of Response (DOR)
From the start date of the first documented response of complete response or partial response and the date defined as the date of the first documented progression or death due to any cause up to 2 years
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Throughout study completion, an average 5 years
Number of participants with trametinib associated serous retinopathy ocular events
screening, week 4, week 8, week 12, week 20 and every 12 weeks after week 20, up to approximately 2 years
Study Arms (2)
Dabrafenib plus Trametinib
EXPERIMENTALEligible participants will receive Dabrafenib 150 mg twice a day (BID) and Trametinib 2 mg once a day (QD) until disease progression as per RECIST 1.1 as confirmed by blinded independent review committee (BIRC), unacceptable toxicity, pregnancy, loss of clinical benefit as determined by the investigator, withdrawal of consent, lost to follow-up, death, or study termination by the sponsor.
Dabrafenib Placebo plus Trametinib Placebo
PLACEBO COMPARATOREligible participants will receive matching placebo for Dabrafenib 150 mg twice a day (BID) and matching placebo for Trametinib 2 mg once a day (QD) until disease progression as per RECIST 1.1 as confirmed by blinded independent review committee (BIRC), unacceptable toxicity, pregnancy, loss of clinical benefit as determined by the investigator, withdrawal of consent, lost to follow-up, death, or study termination by the sponsor.
Interventions
Dabrafenib 150 mg capsule administered orally twice a day (BID)
Trametinib 2 mg tablet administered once a day (QD)
matching placebo tablet for Trametinib 2 mg will be administered orally once a day (QD)
matching placebo capsule for Dabrafenib 150 mg will be administered orally twice a day (BID)
Eligibility Criteria
You may qualify if:
- Signed informed consent
- Male or female ≥ 18 years of age at time of informed consent
- Histologically or cytologically confirmed diagnosis of advanced/metastatic differentiated thyroid carcinoma
- Radioactive-iodine refractory disease
- BRAF V600E mutation-positive tumor sample as per central laboratory result
- Has progressed on at least 1 but not more than 2 prior VEGFR targeted therapies
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- At least one measurable lesion as defined by RECIST v1.1.
You may not qualify if:
- Anaplastic or medullary carcinoma of the thyroid
- Previous treatment with a BRAF inhibitor and/or a MEK inhibitor
- Concomitant RET Fusion-Positive Thyroid Cancer
- Treatment with any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before randomization
- Treatment with any type of anticancer antibody (including investigational antibody) or systemic chemotherapy within 4 weeks before randomization
- Treatment with radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before randomization
- A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (41)
Northwestern University Med School
Chicago, Illinois, 60611, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Novartis Investigative Site
CABA, Buenos Aires, C1417DTB, Argentina
Novartis Investigative Site
Rio de Janiero, Rio de Janeiro, 20231-050, Brazil
Novartis Investigative Site
Blumenau, Santa Catarina, 89015-200, Brazil
Novartis Investigative Site
São Paulo, São Paulo, 01246-000, Brazil
Novartis Investigative Site
Edmonton, Alberta, T6G 1Z2, Canada
Novartis Investigative Site
London, Ontario, N6A 5W9, Canada
Novartis Investigative Site
Fuzhou, Fujian, 350014, China
Novartis Investigative Site
Zhengzhou, Henan, 450008, China
Novartis Investigative Site
Wuhan, Hubei, 430022, China
Novartis Investigative Site
Changsha, Hunan, 410013, China
Novartis Investigative Site
Nanjing, Jiangsu, 210006, China
Novartis Investigative Site
Nanjing, Jiangsu, 210009, China
Novartis Investigative Site
Xuzhou, Jiangsu, 221003, China
Novartis Investigative Site
Changchun, Jilin, 130033, China
Novartis Investigative Site
Chengdu, Sichuan, 610041, China
Novartis Investigative Site
Tianjin, Tianjin Municipality, 300121, China
Novartis Investigative Site
Beijing, 100036, China
Novartis Investigative Site
Beijing, 100730, China
Novartis Investigative Site
Guangzhou, 510060, China
Novartis Investigative Site
Shanghai, 200233, China
Novartis Investigative Site
Tianjin, 300052, China
Novartis Investigative Site
Tianjin, 300480, China
Novartis Investigative Site
Hisar, Haryana, 125005, India
Novartis Investigative Site
New Delhi, National Capital Territory of Delhi, 110029, India
Novartis Investigative Site
Chennai, 600 020, India
Novartis Investigative Site
George Town, Pulau Pinang, 10450, Malaysia
Novartis Investigative Site
Kuching, Sarawak, 93586, Malaysia
Novartis Investigative Site
Kuala Lumpur, 59100, Malaysia
Novartis Investigative Site
Seoul, Korea, 03080, South Korea
Novartis Investigative Site
Seoul, 05505, South Korea
Novartis Investigative Site
Seoul, 06351, South Korea
Novartis Investigative Site
Seoul, 06591, South Korea
Novartis Investigative Site
Tainan, 70403, Taiwan
Novartis Investigative Site
Taipei, 10002, Taiwan
Novartis Investigative Site
Istanbul, Fatih, 34098, Turkey (Türkiye)
Novartis Investigative Site
Edirne, Merkez, 22030, Turkey (Türkiye)
Novartis Investigative Site
Ankara, Yenimahalle, 06500, Turkey (Türkiye)
Novartis Investigative Site
Adana, Yuregir, 01250, Turkey (Türkiye)
Novartis Investigative Site
Hanoi, 100000, Vietnam
MeSH Terms
Interventions
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 22, 2021
First Posted
June 25, 2021
Study Start
November 15, 2021
Primary Completion
January 22, 2025
Study Completion (Estimated)
June 4, 2027
Last Updated
December 2, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.