Rationale and design of DECISION: a double-blind, randomized, placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory, differentiated thyroid cancer

DECISION is a multicenter, double-blind, randomized, placebo-controlled phase III study in patients with locally advanced/metastatic RAI-refractory DTC. Study treatment will continue until radiographically documented disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent. Efficacy will be evaluated every 56 days (2 cycles), whereas safety will be evaluated every 28 days (1 cycle) for the first 8 months and every 56 days thereafter. Following disease progression, patients may continue or start sorafenib, depending on whether they were randomized to receive sorafenib or placebo, at investigator discretion. Patients originally randomized to receive sorafenib will be followed up every 3 months for overall survival (OS); patients originally randomized to receive placebo will be followed up every month for 8 months after cross-over to sorafenib. The duration of the trial is expected to be 30 months from the time the first patient is randomized until the planned number of PFS events is attained. The primary endpoint is PFS; secondary endpoints include OS, time to disease progression, disease control rate, response rate, duration of response, safety, and pharmacokinetic analysis.The DECISION study has been designed to test whether sorafenib improves PFS in patients with locally advanced or metastatic RAI-refractory DTC.ClinicalTrials.gov Identifier: NCT00984282; EudraCT: 2009-012007-25.In the United States in 2010, there were 44,670 estimated new cases of thyroid cancer, making it the most common of the endocrine malignancies [1]. The incidence of thyroid cancer is increasing globally, as is the number of patients who die from this disease [2,3]. Differentiated thyroid cancer (DTC) is the histologic subtype present in most patients, as well as being primarily responsible for the increased overall incidence of thyroid cancer [4].Therapeutic options for patients with radioiodine (RAI)-refractory, advanced DTC are limited. The only systemic therapy