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

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: NCT04940052

Novartis Reference Number: CDRB436J12301

Last Update: Apr 22, 2022

See if you pre-qualify

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)

Condition 
Differentiated Thyroid Cancer
Phase 
Phase 3
Overall status 
Recruiting
Start date 
Nov 15, 2021
Completion date 
Oct 30, 2026
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Dabrafenib
Dabrafenib 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
Drug
Dabrafenib placebo
Dabrafenib placebo will be administered orally twice daily
Drug
Dabrafenib
Dabrafenib 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
Drug
Dabrafenib placebo
Dabrafenib placebo will be administered orally twice daily
Drug
Dabrafenib
Dabrafenib 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
Drug
Dabrafenib placebo
Dabrafenib placebo will be administered orally twice 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 Locations

China
Novartis Investigative Site
Recruiting
Wuhan, 430022
Hubei
China
Novartis Investigative Site
Recruiting
Chengdu, 610041
Sichuan
China
Novartis Investigative Site
Recruiting
Tianjin, 300121
Tianjin
China
Novartis Investigative Site
Recruiting
Tianjin, 300052
-
China
Novartis Investigative Site
Recruiting
Wuhan, 430022
Hubei
China
Novartis Investigative Site
Recruiting
Chengdu, 610041
Sichuan
China
Novartis Investigative Site
Recruiting
Tianjin, 300121
Tianjin
China
Novartis Investigative Site
Recruiting
Tianjin, 300052
-
China
Novartis Investigative Site
Recruiting
Wuhan, 430022
Hubei
China
Novartis Investigative Site
Recruiting
Chengdu, 610041
Sichuan
China
Novartis Investigative Site
Recruiting
Tianjin, 300121
Tianjin
China
Novartis Investigative Site
Recruiting
Tianjin, 300052
-
China
India
Novartis Investigative Site
Recruiting
Mumbai, 400056
Maharashtra
India
Novartis Investigative Site
Recruiting
Mumbai, 400056
Maharashtra
India
Novartis Investigative Site
Recruiting
Mumbai, 400056
Maharashtra
India
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 06591
Seocho Gu
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 03080
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 05505
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 06591
Seocho Gu
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 03080
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 05505
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 06591
Seocho Gu
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 03080
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 05505
-
Korea, Republic of
Malaysia
Novartis Investigative Site
Recruiting
Kuching, 93586
Sarawak
Malaysia
Novartis Investigative Site
Recruiting
Kuala Lumpur, 50586
Wilayah Persekutuan
Malaysia
Novartis Investigative Site
Recruiting
Kuala Lumpur, 59100
-
Malaysia
Novartis Investigative Site
Recruiting
Pulau Pinang, 10990
-
Malaysia
Novartis Investigative Site
Recruiting
Kuching, 93586
Sarawak
Malaysia
Novartis Investigative Site
Recruiting
Kuala Lumpur, 50586
Wilayah Persekutuan
Malaysia
Novartis Investigative Site
Recruiting
Kuala Lumpur, 59100
-
Malaysia
Novartis Investigative Site
Recruiting
Pulau Pinang, 10990
-
Malaysia
Novartis Investigative Site
Recruiting
Kuching, 93586
Sarawak
Malaysia
Novartis Investigative Site
Recruiting
Kuala Lumpur, 50586
Wilayah Persekutuan
Malaysia
Novartis Investigative Site
Recruiting
Kuala Lumpur, 59100
-
Malaysia
Novartis Investigative Site
Recruiting
Pulau Pinang, 10990
-
Malaysia
Taiwan
Novartis Investigative Site
Recruiting
Tainan, 70403
-
Taiwan
Novartis Investigative Site
Recruiting
Taipei, 10048
-
Taiwan
Novartis Investigative Site
Recruiting
Tainan, 70403
-
Taiwan
Novartis Investigative Site
Recruiting
Taipei, 10048
-
Taiwan
Novartis Investigative Site
Recruiting
Tainan, 70403
-
Taiwan
Novartis Investigative Site
Recruiting
Taipei, 10048
-
Taiwan
Turkey
Novartis Investigative Site
Recruiting
Istanbul, 34098
TUR
Turkey
Novartis Investigative Site
Recruiting
Adana, 01250
-
Turkey
Novartis Investigative Site
Recruiting
Ankara, 06100
-
Turkey
Novartis Investigative Site
Recruiting
Ankara, 06560
-
Turkey
Novartis Investigative Site
Recruiting
Edirne, 22030
-
Turkey
Novartis Investigative Site
Recruiting
Istanbul, 34098
TUR
Turkey
Novartis Investigative Site
Recruiting
Adana, 01250
-
Turkey
Novartis Investigative Site
Recruiting
Ankara, 06100
-
Turkey
Novartis Investigative Site
Recruiting
Ankara, 06560
-
Turkey
Novartis Investigative Site
Recruiting
Edirne, 22030
-
Turkey
Novartis Investigative Site
Recruiting
Istanbul, 34098
TUR
Turkey
Novartis Investigative Site
Recruiting
Adana, 01250
-
Turkey
Novartis Investigative Site
Recruiting
Ankara, 06100
-
Turkey
Novartis Investigative Site
Recruiting
Ankara, 06560
-
Turkey
Novartis Investigative Site
Recruiting
Edirne, 22030
-
Turkey

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 

Have a question?

Call 1-888-669-6682 or email [email protected]