Back to resultsStudy of 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
Primary Purpose
Differentiated Thyroid Cancer
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Dabrafenib
Trametinib
Trametinib placebo
Dabrafenib placebo
Sponsored by
About this trial
This is an interventional treatment trial for Differentiated Thyroid Cancer focused on measuring Locally advanced or metastatic differentiated thyroid cancer, radio active iodine refractory, previously targeted therapy, BRAFV600E mutation, dabrafenib, trametinib
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
Sites / Locations
- Massachusetts General Hospital Dept. of MGH (2)Recruiting
- Novartis Investigative SiteRecruiting
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Dabrafenib plus trametinib
Placebo dabrafenib plus placebo trametinib
Arm Description
Participants will be treated with dabrafenib twice daily and trametinib once daily
Participants will receive placebo dabrafenib twice daily and placebo trametinib once daily
Outcomes
Primary Outcome Measures
Progression Free Survival
Progression Free Survival is based on the blinded independent review committee assessment using RECIST 1.1
Secondary Outcome Measures
Overall Response Rate
overall response rate is defined as the proportion of patients with best overall response of complete response or partial response assessed per blinded independent review committee using RECIST 1.1 criteria
Overall Survival
Overall survival is defined as the time from the date of randomization to the date of death to any cause.
Duration of response
Duration of response only applies to patients whose best overall response is complete response or partial response according to RECIST 1.1 and based on blinded independent review committee.
Number of participants with trametinib associated serous retinopathy ocular events
Standard ophthalmic examination will by done by an ophthalmologist and optical coherence tomography conducted at mandated visit. Analysis using optical coherence tomography data will be done to assess the incidence, type and severity of ocular events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04940052
Brief Title
Study of 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
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 15, 2021 (Actual)
Primary Completion Date
April 19, 2024 (Anticipated)
Study Completion Date
October 30, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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)
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 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Differentiated Thyroid Cancer
Keywords
Locally advanced or metastatic differentiated thyroid cancer, radio active iodine refractory, previously targeted therapy, BRAFV600E mutation, dabrafenib, trametinib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
150 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dabrafenib plus trametinib
Arm Type
Experimental
Arm Description
Participants will be treated with dabrafenib twice daily and trametinib once daily
Arm Title
Placebo dabrafenib plus placebo trametinib
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo dabrafenib twice daily and placebo trametinib once daily
Intervention Type
Drug
Intervention Name(s)
Dabrafenib
Intervention Description
Dabrafenib will be administered orally twice daily
Intervention Type
Drug
Intervention Name(s)
Trametinib
Intervention Description
Trametinib will be administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Trametinib placebo
Intervention Description
Trametinib will be administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Dabrafenib placebo
Intervention Description
Dabrafenib placebo will be administered orally twice daily
Primary Outcome Measure Information:
Title
Progression Free Survival
Description
Progression Free Survival is based on the blinded independent review committee assessment using RECIST 1.1
Time Frame
From randomization to first documented progression or deaths, whichever comes first, assessed up to approximately 2 years
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
overall response rate is defined as the proportion of patients with best overall response of complete response or partial response assessed per blinded independent review committee using RECIST 1.1 criteria
Time Frame
From randomization up to approximately 2 years
Title
Overall Survival
Description
Overall survival is defined as the time from the date of randomization to the date of death to any cause.
Time Frame
From randomization to death assessed up to approximately 5 years
Title
Duration of response
Description
Duration of response only applies to patients whose best overall response is complete response or partial response according to RECIST 1.1 and based on blinded independent review committee.
Time Frame
Duration of response 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
Title
Number of participants with trametinib associated serous retinopathy ocular events
Description
Standard ophthalmic examination will by done by an ophthalmologist and optical coherence tomography conducted at mandated visit. Analysis using optical coherence tomography data will be done to assess the incidence, type and severity of ocular events
Time Frame
screening, week 4, week 8, week 12, week 20 and every 12 weeks after week 20, up to approximately 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
1-888-669-6682
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Facility Information:
Facility Name
Massachusetts General Hospital Dept. of MGH (2)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brittany Bertaux
Email
bbertaux@mgh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Lori J. Wirth
Facility Name
Novartis Investigative Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1417DTB
Country
Argentina
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Buenos Aires
ZIP/Postal Code
C1012AAR
Country
Argentina
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Rio De Janiero
State/Province
RJ
ZIP/Postal Code
20231-050
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
91350 200
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Blumenau
State/Province
Santa Catarina
ZIP/Postal Code
89015-200
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
01246-000
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Sao Paulo
ZIP/Postal Code
01323-900
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350013
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450008
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430022
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210006
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210009
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Xuzhou
State/Province
Jiangsu
ZIP/Postal Code
221003
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130033
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
XI An
State/Province
Shanxi
ZIP/Postal Code
710061
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Xi'an
State/Province
Shanxi
ZIP/Postal Code
710032
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300060
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300121
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kunming City
State/Province
Yunnan
ZIP/Postal Code
650000
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310014
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100036
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Changsha
ZIP/Postal Code
410013
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Guangzhou
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200233
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Tianjin
ZIP/Postal Code
300052
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Hisar
State/Province
Haryana
ZIP/Postal Code
125005
Country
India
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400056
Country
India
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Vellore
State/Province
Tamil Nadu
ZIP/Postal Code
632 004
Country
India
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Hyderabad
State/Province
Telangana
ZIP/Postal Code
500082
Country
India
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Chennai
ZIP/Postal Code
600 020
Country
India
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
New Delhi
ZIP/Postal Code
110029
Country
India
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Seocho Gu
ZIP/Postal Code
06591
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kuching
State/Province
Sarawak
ZIP/Postal Code
93586
Country
Malaysia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kuala Lumpur
State/Province
Wilayah Persekutuan
ZIP/Postal Code
50586
Country
Malaysia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kuala Lumpur
ZIP/Postal Code
59100
Country
Malaysia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Pulau Pinang
ZIP/Postal Code
10990
Country
Malaysia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Ciudad de Mexico
State/Province
Mexico CP
ZIP/Postal Code
14080
Country
Mexico
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Monterrey
State/Province
Nuevo Leon
ZIP/Postal Code
64460
Country
Mexico
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Chihuahua
ZIP/Postal Code
31210
Country
Mexico
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Tainan
ZIP/Postal Code
70403
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10048
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Istanbul
State/Province
TUR
ZIP/Postal Code
34098
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Adana
ZIP/Postal Code
01250
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06560
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Edirne
ZIP/Postal Code
22030
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Hanoi
ZIP/Postal Code
100000
Country
Vietnam
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
Learn more about this trial
Study of 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
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