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: Sep 07, 2022

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

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