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.
Author(s): Brose MS, Nutting CM, Sherman SI, Shong YK, Smit JW, Reike G, Chung J, Kalmus J,
Kappeler C, Schlumberger M.
Affiliation(s): 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
Publication date & source: 2011, BMC Cancer. , 11:349
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.
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