Clinical trial NCT00984282: Nexavar® Versus Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer
Official title: A Double-Blind Randomized Phase III Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Thyroid Neoplasms
Keywords: RAI-Refractory
Differentiated
Follicular
Papillary
Hurthle
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2009-09-25
Enrollment: 417
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Trial of sorafenib versus placebo in the treatment of locally advanced or metastatic differentiated thyroid cancer refractory to radioiodine

Detailed description: Eligible subjects were randomized 1:1 to sorafenib 800 mg daily or matching placebo. Progression was assessed every 8 weeks by modified RECIST criteria. Subjects had the option to unblind study treatment after progression and to receive open label sorafenib regardless of initial treatment assignment. Following discontinuation of study treatment, subjects were followed for survival every 3 months in long-term follow-up. Subjects who terminated study treatment (either double only or double blind and open label) for reasons other than death, lost to follow-up or consent withdrawn entered long-term follow up

Eligibility criteria: Inclusion Criteria:

* Locally advanced or metastatic differentiated thyroid cancer (papillary, follicular and Hurthle cell)
* Poorly differentiated and other thyroid variants (e.g. insular, tall cell, etc.) are eligible provided that the histology has no medullary differentiation nor anaplastic features
* Progression within 14 months (RECIST \[Response Evaluation Criteria in Solid Tumors\] should be used as a basis for the assessment of disease progression)
* RAI (radioactive iodine) refractory

Exclusion Criteria:

* Histologic subtypes of thyroid cancer other than differentiated (i.e. like anaplastic and medullary carcinoma, lymphoma or sarcoma)
* Prior anti-cancer treatment with tyrosine kinase inhibitors, monoclonal antibodies (licensed or investigational) that target VEGF (vascular endothelial growth factor) or VEGF Receptors or other targeted agents
* Prior anti-cancer treatment for thyroid cancer with use of chemotherapy (low dose chemotherapy for radiosensitization is allowed) or Thalidomide or any of its derivatives

Primary outcomes:
measure: Progression-free Survival (PFS) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation
timeFrame: Final analysis to be performed when approximately 267 progression-free survival events (centrally assessed) had occurred, study duration approximately three years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization of the first subject until the database cut-off (30 AUG 2017), study duration approximately eight years
measure: Time to Progression (TTP) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation
timeFrame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
measure: Disease Control Rate (DCR) Based on Central Assessment
timeFrame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
measure: Response Rate Based on Central Assessment
timeFrame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
measure: Duration of Response (DOR) Based on Central Assessment
timeFrame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
measure: Maximum Percent Reduction in Target Lesion Size Based on Central Assessment
timeFrame: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
measure: AUC(0-12h),ss (Area Under the Concentration Time Curve From Time 0 to 12 Hours at Steady State)
timeFrame: A single pharmacokinetic plasma sample was collected at steady state (after 14 days of uninterrupted, unmodified sorafenib dosing)
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Stanford
country: United States
state: California
city: New Haven
country: United States
state: Connecticut
city: Atlanta
country: United States
state: Georgia
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Albuquerque
country: United States
state: New Mexico
city: New York
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Wien
country: Austria
city: Bruxelles - Brussel
country: Belgium
city: Sofia
country: Bulgaria
city: Guangzhou
country: China
state: Guangdong
city: Beijing
country: China
city: Beijing
country: China
city: Chengdu
country: China
city: Hangzhou
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Tianjin
country: China
city: Odense C
country: Denmark
city: Angers
country: France
city: Bordeaux
country: France
city: Caen
country: France
city: LILLE cedex
country: France
city: Lyon
country: France
city: MARSEILLE cedex
country: France
city: Paris
country: France
city: Villejuif
country: France
city: Erlangen
country: Germany
state: Bayern
city: München
country: Germany
state: Bayern
city: Würzburg
country: Germany
state: Bayern
city: Essen
country: Germany
state: Nordrhein-Westfalen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
state: Sachsen
city: Napoli
country: Italy
state: Campania
city: Genova
country: Italy
state: Liguria
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Catania
country: Italy
state: Sicilia
city: Pisa
country: Italy
state: Toscana
city: Siena
country: Italy
state: Toscana
city: Perugia
country: Italy
state: Umbria
city: Nagoya
country: Japan
state: Aichi
city: Nagoya
country: Japan
state: Aichi
city: Kashiwa
country: Japan
state: Chiba
city: Koto-ku
country: Japan
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Daejeon
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Groningen
country: Netherlands
city: Leiden
country: Netherlands
city: Gliwice
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Obninsk
country: Russian Federation
city: Riyadh
country: Saudi Arabia
city: Majadahonda
country: Spain
state: Madrid
city: Barcelona
country: Spain
city: Göteborg
country: Sweden
city: Linköping
country: Sweden
city: Lund
country: Sweden
city: Stockholm
country: Sweden
city: Aberdeen
country: United Kingdom
state: Aberdeenshire
city: Cardiff
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Worden F, Fassnacht M, Shi Y, Hadjieva T, Bonichon F, Gao M, Fugazzola L, Ando Y, Hasegawa Y, Park DJ, Shong YK, Smit JW, Chung J, Kappeler C, Meinhardt G, Schlumberger M, Brose MS. Safety and tolerability of sorafenib in patients with radioiodine-refractory thyroid cancer. Endocr Relat Cancer. 2015 Dec;22(6):877-87. doi: 10.1530/ERC-15-0252.
citation: Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, de la Fouchardiere C, Pacini F, Paschke R, Shong YK, Sherman SI, Smit JW, Chung J, Kappeler C, Pena C, Molnar I, Schlumberger MJ; DECISION investigators. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014 Jul 26;384(9940):319-28. doi: 10.1016/S0140-6736(14)60421-9. Epub 2014 Apr 24.
citation: Brose MS, Nutting CM, Sherman SI, Shong YK, Smit JW, Reike G, Chung J, Kalmus J, Kappeler C, Schlumberger M. 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. 2011 Aug 11;11:349. doi: 10.1186/1471-2407-11-349.
citation: Brose MS, Schlumbeger M, Jeffers M, Kappeler C, Meinhardt G, Pena CEA. Analysis of Biomarkers and Association With Clinical Outcomes in Patients With Differentiated Thyroid Cancer: Subanalysis of the Sorafenib Phase III DECISION Trial. Clin Cancer Res. 2019 Dec 15;25(24):7370-7380. doi: 10.1158/1078-0432.CCR-18-3439. Epub 2019 Sep 26.
citation: Capdevila J, Matos I, Mancuso FM, Iglesias C, Nuciforo P, Zafon C, Palmer HG, Ogbah Z, Muinos L, Hernando J, Villacampa G, Pena CE, Tabernero J, Brose MS, Schlumberger M, Vivancos A. Identification of Expression Profiles Defining Distinct Prognostic Subsets of Radioactive-Iodine Refractory Differentiated Thyroid Cancer from the DECISION Trial. Mol Cancer Ther. 2020 Jan;19(1):312-317. doi: 10.1158/1535-7163.MCT-19-0211. Epub 2019 Sep 20.