Last Update: Dec 05, 2023
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)
ClinicalTrials.gov Identifier:
Novartis Reference Number:CDRB436J12301
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

150 adults 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 will enter in the trial. 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 (1versus2) and prior lenvatinib treatment (yes versus no)

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 cancer who are refractory to radioactive iodine and have progressed following prior VEGFR targeted therapy. After eligibility assessment, approximately 150 patients will be randomized in a 2:1 ratio to either dabrafenib plus trametinib or placebo. Patients will receive dabrafenib in combination with trametinib or placebo until disease progression as per RECIST 1.1 as determined by investigator and confirmed by BIRC or loss of clinical benefit as determined by investigator, death, unacceptable toxicity, pregnancy, withdrawal of consent, lost to follow-up or early termination of the study by the sponsor. Patients randomized in the placebo arm and for whom progression as per RECIST 1.1 is confirmed by blinded independent review committee and who meet the criteria will be given the option to cross over to the open label combination drug dabrafenib plus trametinib

Differentiated Thyroid Cancer
Phase 3
Recruiting
150
Nov 15, 2021
Oct 30, 2026
All
18 Years - (Adult, Older Adult)

Interventions

Drug

Dabrafenib

Dabrafenib will be administered orally twice daily
Drug

Dabrafenib placebo

Dabrafenib placebo will be administered orally twice daily
Drug

Trametinib

Trametinib will be administered orally once daily
Drug

Trametinib placebo

Trametinib will be administered orally once daily

Eligibility Criteria

Inclusion Criteria:

Signed informed consent must be obtained prior to performing any specific pre-screening and screening procedure
Male or female >= 18 years of age at the time of informed consent
Histologically or cytologically confirmed diagnosis of advanced/metastatic differentiated thyroid cancer
Radio active iodine refractory disease
BRAFV600E mutation positive tumor sample as per Novartis designated central laboratory result
Has progressed on at least 1 but not more than 2 prior VEGFR targeted therapy
Eastern Cooperative Oncology Group performance status >= 2
At least one measurable lesion as defined by RECIST 1.1

Exclusion Criteria:

Anaplastic or medullary carcinoma of the Tyroid
Previous treatment with BRAF inhibitor and/or MEK inhibitor
Concomitant RET Fusion Positive Thyroid cancer
Receipt of any type of small molecule kinase inhibitor within 2 weeks before randomization
Receipt of any type of cancer antibody or systemic chemotherapy within 4 weeks before randomization
Receipt of 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 or central serous retinopathy

Study Location

Novartis Investigative Site

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Caba,Buenos Aires,C1417DTB,Argentina

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Buenos Aires,C1012AAR,Argentina

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Porto Alegre,RS,91350 200,Brazil

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Rio De Janiero,RJ,20231-050,Brazil

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Blumenau,Santa Catarina,89015-200,Brazil

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Sao Paulo,01323-900,Brazil

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Sao Paulo,SP,01246-000,Brazil

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Calgary,Alberta,T2N 4N2,Canada

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London,Ontario,N6A 5W9,Canada

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Edmonton,Alberta,T6G 1Z2,Canada

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Toronto,Ontario,M5G 2M9,Canada

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Nanjing,Jiangsu,210009,China

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XI An,Shanxi,710061,China

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Tianjin,300052,China

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Kunming City,Yunnan,650000,China

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Xi'an,Shanxi,710032,China

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Tianjin,Tianjin,300121,China

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Changchun,Jilin,130033,China

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Xuzhou,Jiangsu,221003,China

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Beijing,100036,China

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Tianjin,Tianjin,300480,China

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Changsha,410013,China

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Beijing,100730,China

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Fuzhou,Fujian,350013,China

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Chengdu,Sichuan,610041,China

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Shanghai,200233,China

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Guangzhou,510060,China

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Nanjing,Jiangsu,210006,China

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Zhengzhou,Henan,450008,China

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Hangzhou,Zhejiang,310014,China

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Wuhan,Hubei,430022,China

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New Delhi,110029,India

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Hisar,Haryana,125005,India

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Hyderabad,Telangana,500082,India

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Mumbai,Maharashtra,400056,India

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Vellore,Tamil Nadu,632 004,India

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Chennai,600 020,India

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Seoul,03080,Korea, Republic of

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Seoul,05505,Korea, Republic of

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Seoul,06351,Korea, Republic of

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Seoul,Seocho Gu,06591,Korea, Republic of

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Kuching,Sarawak,93586,Malaysia

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Pulau Pinang,10990,Malaysia

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Kuala Lumpur,59100,Malaysia

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Kuala Lumpur,Wilayah Persekutuan,50586,Malaysia

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Chihuahua,31210,Mexico

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Ciudad de Mexico,Mexico CP,14080,Mexico

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Monterrey,Nuevo Leon,64460,Mexico

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Taipei,10048,Taiwan

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Tainan,70403,Taiwan

Novartis Investigative Site

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Adana,01250,Turkey

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Ankara,06100,Turkey

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Ankara,06560,Turkey

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Edirne,22030,Turkey

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Istanbul,TUR,34098,Turkey

Massachusetts General Hospital Dept. of MGH (2)

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Boston,Zachary Castellarin email: [email protected] -- Lori J. Wirth,02114 - Massachusetts,United States

Northwestern University Medical School

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Chicago,(312-926-7358) -- Jochen Lorch,60611 - Illinois,United States

Novartis Investigative Site

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Hanoi,100000,Vietnam

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