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)

CDRB436J12301

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)

2021-11-15

2027-05-26

2027-06-23

Recruiting

Early phase I

150

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 150, 'type': 'ESTIMATED'}}

2024-05-07