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

NCT ID: NCT04940052

Last Updated: 2025-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

153 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-15

Study Completion Date

2027-06-04

Brief Summary

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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

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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

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Differentiated Thyroid Cancer (DTC)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Patients will be randomized in a 2:1 ratio to either dabrafenib plus trametinib or placebo. Patients will be stratified by number of prior VEGFR targeted therapy (1 versus 2) and prior Lenvatinib treatment (yes versus no).
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Dabrafenib plus Trametinib

Eligible 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.

Group Type EXPERIMENTAL

Dabrafenib

Intervention Type DRUG

Dabrafenib 150 mg capsule administered orally twice a day (BID)

Trametinib

Intervention Type DRUG

Trametinib 2 mg tablet administered once a day (QD)

Dabrafenib Placebo plus Trametinib Placebo

Eligible 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.

Group Type PLACEBO_COMPARATOR

Trametinib Placebo

Intervention Type DRUG

matching placebo tablet for Trametinib 2 mg will be administered orally once a day (QD)

Dabrafenib placebo

Intervention Type DRUG

matching placebo capsule for Dabrafenib 150 mg will be administered orally twice a day (BID)

Interventions

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Dabrafenib

Dabrafenib 150 mg capsule administered orally twice a day (BID)

Intervention Type DRUG

Trametinib

Trametinib 2 mg tablet administered once a day (QD)

Intervention Type DRUG

Trametinib Placebo

matching placebo tablet for Trametinib 2 mg will be administered orally once a day (QD)

Intervention Type DRUG

Dabrafenib placebo

matching placebo capsule for Dabrafenib 150 mg will be administered orally twice a day (BID)

Intervention Type DRUG

Other Intervention Names

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DRB436 TMT212

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Northwestern University Med School

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Site Status

Novartis Investigative Site

Rio de Janiero, Rio de Janeiro, Brazil

Site Status

Novartis Investigative Site

Blumenau, Santa Catarina, Brazil

Site Status

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Site Status

Novartis Investigative Site

Edmonton, Alberta, Canada

Site Status

Novartis Investigative Site

London, Ontario, Canada

Site Status

Novartis Investigative Site

Fuzhou, Fujian, China

Site Status

Novartis Investigative Site

Zhengzhou, Henan, China

Site Status

Novartis Investigative Site

Wuhan, Hubei, China

Site Status

Novartis Investigative Site

Changsha, Hunan, China

Site Status

Novartis Investigative Site

Nanjing, Jiangsu, China

Site Status

Novartis Investigative Site

Nanjing, Jiangsu, China

Site Status

Novartis Investigative Site

Xuzhou, Jiangsu, China

Site Status

Novartis Investigative Site

Changchun, Jilin, China

Site Status

Novartis Investigative Site

Chengdu, Sichuan, China

Site Status

Novartis Investigative Site

Tianjin, Tianjin Municipality, China

Site Status

Novartis Investigative Site

Beijing, , China

Site Status

Novartis Investigative Site

Beijing, , China

Site Status

Novartis Investigative Site

Guangzhou, , China

Site Status

Novartis Investigative Site

Shanghai, , China

Site Status

Novartis Investigative Site

Tianjin, , China

Site Status

Novartis Investigative Site

Tianjin, , China

Site Status

Novartis Investigative Site

Hisar, Haryana, India

Site Status

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, India

Site Status

Novartis Investigative Site

Chennai, , India

Site Status

Novartis Investigative Site

George Town, Pulau Pinang, Malaysia

Site Status

Novartis Investigative Site

Kuching, Sarawak, Malaysia

Site Status

Novartis Investigative Site

Kuala Lumpur, , Malaysia

Site Status

Novartis Investigative Site

Seoul, Korea, South Korea

Site Status

Novartis Investigative Site

Seoul, , South Korea

Site Status

Novartis Investigative Site

Seoul, , South Korea

Site Status

Novartis Investigative Site

Seoul, , South Korea

Site Status

Novartis Investigative Site

Tainan, , Taiwan

Site Status

Novartis Investigative Site

Taipei, , Taiwan

Site Status

Novartis Investigative Site

Istanbul, Fatih, Turkey (Türkiye)

Site Status

Novartis Investigative Site

Edirne, Merkez, Turkey (Türkiye)

Site Status

Novartis Investigative Site

Ankara, Yenimahalle, Turkey (Türkiye)

Site Status

Novartis Investigative Site

Adana, Yuregir, Turkey (Türkiye)

Site Status

Novartis Investigative Site

Hanoi, , Vietnam

Site Status

Countries

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United States Argentina Brazil Canada China India Malaysia South Korea Taiwan Turkey (Türkiye) Vietnam

Other Identifiers

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CDRB436J12301

Identifier Type: -

Identifier Source: org_study_id

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