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

Titre officiel

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)

Sommaire:

Au total, 150 adultes atteints d’un carcinome thyroïdien différencié, localement avancé ou métastatique, présentant la mutation BRAFV600E, réfractaire à l’iode radioactif et ayant progressé après un traitement antérieur ciblant le VEGFR, participeront à l’essai. Les patients seront répartis de façon aléatoire, selon un rapport 2:1, dans le groupe sous dabrafénib et tramétinib ou dans le groupe sous placebo. Les patients seront répartis en fonction du nombre de traitements antérieurs ciblant le VEGFR (1 contre 2) et de l’administration ou non d’un traitement antérieur par lenvatinib (oui ou non).

Description de l'essai

Primary Outcome:

• Progression Free Survival

Secondary Outcome:

• Overall Response Rate
• Overall Survival
• Duration of response
• Number of participants with trametinib associated serous retinopathy ocular events

This is a global, multicentre, 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

Voir cet essai sur ClinicalTrials.gov