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

BMC Cancer

Study Protocol

Christian Kappeler¹  Joachim Kalmus¹  Gerhard Reike¹  Steven I Sherman²  Young Kee Shong³  Johannes WA Smit⁴  Marcia S Brose⁵  Christopher M Nutting⁶  Martin Schlumberger⁷  John Chung⁸ 

[1] Bayer Schering Pharma AG, Mullerstrasse 178, 13353, Berlin, Germany;Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Endocrine Multidisciplinary Center, Unit 1461, 1400 Pressler Street, 77230-1402, Houston, TX, USA;Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, 138-736, Seoul, South Korea;Department of Medicine, Endocrinology, and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333, ZA Leiden, The Netherlands;Department of Otorhinolaryngology: Head and Neck Surgery, Department of Medicine, Division of Hematology/Oncology, The University of Pennsylvania, Abramson Cancer Center, Clinical Research Building, Room 127, 425 Curie Boulevard, 19104, Philadelphia, PA, USA;Head and Neck Unit, Royal Marsden Hospital, Fulham Road, SW3 6JJ, London, UK;Institut Gustave Roussy, rue Camille Desmoulins, 94805, Villejuif Cédex, France;US Medical Sciences, Oncology, Bayer HealthCare Pharmaceuticals, 6 West Belt, 07470, Wayne, NJ, USA;

关键词: Vascular Endothelial Growth Factor;    Overall Survival;    Thyroid Cancer;    Sorafenib;    Differentiate Thyroid Cancer;   

DOI  :  10.1186/1471-2407-11-349

 received in 2011-03-23, accepted in 2011-08-11,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe 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/designDECISION 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.DiscussionThe DECISION study has been designed to test whether sorafenib improves PFS in patients with locally advanced or metastatic RAI-refractory DTC.Trial RegistrationClinicalTrials.gov Identifier: NCT00984282; EudraCT: 2009-012007-25.

【 授权许可】

CC BY   
© Brose et al; licensee BioMed Central Ltd. 2011