title: 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.
abstract: BACKGROUND
  The incidence of thyroid cancer and the number of patients who die from this disease are increasing globally. Differentiated thyroid cancer (DTC) is the histologic subtype present in most patients and is primarily responsible for the increased overall incidence of thyroid cancer. Sorafenib is a multikinase inhibitor that targets several molecular signals believed to be involved in the pathogenesis of thyroid cancer, including those implicated in DTC. In phase II studies of patients with DTC, sorafenib treatment has yielded a median progression-free survival (PFS) of 58 to 84 weeks and disease control rates of 59% to 100%. The DECISION trial was designed to assess the ability of sorafenib to improve PFS in patients with locally advanced or metastatic, radioactive iodine (RAI)-refractory DTC.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  The DECISION study has been designed to test whether sorafenib improves PFS in patients with locally advanced or metastatic RAI-refractory DTC.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT00984282; EudraCT: 2009-012007-25.
authors.affiliation: Department of Otorhinolaryngology: Head and Neck Surgery, The University of Pennsylvania, Abramson Cancer Center, Clinical Research Building, Room 127, 425 Curie Boulevard, Philadelphia, PA 19104, USA. brosem@mail.med.upenn.edu
authors.forename: Marcia S
authors.initials: MS
authors.lastname: Brose
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Nutting
authors.forename: Steven I
authors.initials: SI
authors.lastname: Sherman
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Shong
authors.forename: Johannes W A
authors.initials: JW
authors.lastname: Smit
authors.forename: Gerhard
authors.initials: G
authors.lastname: Reike
authors.forename: John
authors.initials: J
authors.lastname: Chung
authors.forename: Joachim
authors.initials: J
authors.lastname: Kalmus
authors.forename: Christian
authors.initials: C
authors.lastname: Kappeler
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D002985:Clinical Protocols; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D000077157:Sorafenib; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007457:Iodine Radioisotopes; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib