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
Interventions
Dabrafenib
Dabrafenib placebo
Trametinib
Trametinib placebo
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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Buenos Aires,C1012AAR,Argentina
Novartis Investigative Site
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Caba,Buenos Aires,C1417DTB,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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Sao Paulo,01323-900,Brazil
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Blumenau,Santa Catarina,89015-200,Brazil
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Sao Paulo,SP,01246-000,Brazil
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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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Xi'an,Shanxi,710032,China
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Tianjin,300480,China
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Changchun,Jilin,130033,China
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Xuzhou,Jiangsu,221003,China
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Tianjin,Tianjin,300121,China
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Changsha,410013,China
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Zhengzhou,Henan,450008,China
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Beijing,100036,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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Beijing,100730,China
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Guangzhou,510060,China
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Nanjing,Jiangsu,210006,China
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Hangzhou,Zhejiang,310014,China
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Wuhan,Hubei,430022,China
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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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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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New Delhi,110029,India
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Seoul,06351,Korea, Republic of
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Seoul,Seocho Gu,06591,Korea, Republic of
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Seoul,03080,Korea, Republic of
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Seoul,05505,Korea, Republic of
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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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Kuching,Sarawak,93586,Malaysia
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Monterrey,Nuevo Leon,64460,Mexico
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Chihuahua,31210,Mexico
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Ciudad de Mexico,Mexico CP,14080,Mexico
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Tainan,70403,Taiwan
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Taipei,10048,Taiwan
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Ankara,06100,Turkey
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Edirne,22030,Turkey
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Ankara,06560,Turkey
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Istanbul,TUR,34098,Turkey
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Adana,01250,Turkey
Massachusetts General Hospital Dept. of MGH (2)
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Boston,Lara Wellis email: [email protected] -- Lori J. Wirth,02114 - Massachusetts,United States
Northwestern University Med 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
Worldwide Contacts
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