Open Access Highly Accessed Study protocol

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

Marcia S Brose1*, Christopher M Nutting2, Steven I Sherman3, Young Kee Shong4, Johannes WA Smit5, Gerhard Reike6, John Chung7, Joachim Kalmus6, Christian Kappeler6 and Martin Schlumberger8*

Author affiliations

1 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, Philadelphia, PA 19104 USA

2 Head and Neck Unit, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK

3 Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Endocrine Multidisciplinary Center, Unit 1461, 1400 Pressler Street, Houston, TX 77230-1402 USA

4 Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, Korea

5 Department of Medicine, Endocrinology, and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands

6 Bayer Schering Pharma AG, Mullerstrasse 178, 13353 Berlin, Germany

7 US Medical Sciences, Oncology, Bayer HealthCare Pharmaceuticals, 6 West Belt, Wayne, NJ 07470 USA

8 Institut Gustave Roussy, rue Camille Desmoulins, 94805 Villejuif Cédex, France

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Citation and License

BMC Cancer 2011, 11:349  doi:10.1186/1471-2407-11-349

Published: 11 August 2011

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/design

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.

Discussion

The DECISION study has been designed to test whether sorafenib improves PFS in patients with locally advanced or metastatic RAI-refractory DTC.

Trial Registration

ClinicalTrials.gov Identifier: NCT00984282; EudraCT: 2009-012007-25.