Overview
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)
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
Eligibility
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
