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Thyroid NeoplasmsPhase 3NCT00984282

Nexavar® Versus Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer

A Phase 3 study testing Sorafenib (Nexavar, BAY43-9006) in people with Thyroid Neoplasms, run by Bayer at 81 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Trial of sorafenib versus placebo in the treatment of locally advanced or metastatic differentiated thyroid cancer refractory to radioiodine Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Thyroid Neoplasms
What is being tested?
Sorafenib (Nexavar, BAY43-9006)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
417 participants
Where
81 sitesin 18 countries
Study dates
15 Oct 2009to 30 Aug 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

81 sites in 18 countries.

81 sites in 18 countries

United States13 sites

  • Study site

    Albuquerque, New Mexico, 87106

  • Study site

    Ann Arbor, Michigan, 48109

  • Study site

    Atlanta, Georgia, 30322

  • Study site

    Boston, Massachusetts, 02118

  • Study site

    Houston, Texas, 77030

  • Study site

    Los Angeles, California, 90048

  • Study site

    New Haven, Connecticut, 06520

  • Study site

    New York, New York, 10029

  • Study site

    Philadelphia, Pennsylvania, 19104

  • Study site

    Pittsburgh, Pennsylvania, 15213-1863

  • Study site

    Seattle, Washington, 98109-1023

  • Study site

    St Louis, Missouri, 63110

  • Study site

    Stanford, California, 94305-5820

Other trials in United States

Italy9 sites

  • Study site

    Catania, Sicily, 95029

  • Study site

    Genoa, Liguria, 16132

  • Study site

    Milan, Lombardy, 20122

  • Study site

    Milan, Lombardy, 20133

  • Study site

    Milan, Lombardy, 20162

  • Study site

    Naples, Campania, 80131

  • Study site

    Perugia, Umbria, 06126

  • Study site

    Pisa, Tuscany, 56124

  • Study site

    Siena, Tuscany, 53100

Other trials in Italy

United Kingdom9 sites

  • Study site

    Aberdeen, Aberdeenshire, AB25 2ZN

  • Study site

    Cardiff, CF14 2TL

  • Study site

    Glasgow, G12 0YN

  • Study site

    Leeds, LS9 7TF

  • Study site

    London, SE1 9RT

  • Study site

    London, SM2 5PT

  • Study site

    Manchester, M20 4BX

  • Study site

    Newcastle upon Tyne, NE7 7DN

  • Study site

    Sutton, SM2 5PT

Other trials in United Kingdom

China8 sites

  • Study site

    Beijing, 100021

  • Study site

    Beijing, 100730

  • Study site

    Chengdu, 610041

  • Study site

    Guangzhou, Guangdong, 510060

  • Study site

    Hangzhou, 310022

  • Study site

    Shanghai, 200030

  • Study site

    Shanghai, 200127

  • Study site

    Tianjin, 300060

Other trials in China

France8 sites

  • Study site

    Angers, 49933

  • Study site

    Bordeaux, 33076

  • Study site

    Caen, 14076

  • Study site

    Lille, 59037

  • Study site

    Lyon, 69373

  • Study site

    Marseille, 13273

  • Study site

    Paris, 75651

  • Study site

    Villejuif, 94805

Other trials in France

Germany6 sites

  • Study site

    Cologne, North Rhine-Westphalia, 50924

  • Study site

    Erlangen, Bavaria, 91054

  • Study site

    Essen, North Rhine-Westphalia, 45122

  • Study site

    Leipzig, Saxony, 04103

  • Study site

    München, Bavaria, 81377

  • Study site

    Würzburg, Bavaria, 97080

Other trials in Germany

South Korea6 sites

  • Study site

    Daejeon, 301-721

  • Asan Medical Center

    Seoul, Seoul Teugbyeolsi, 138-736

  • Study site

    Seoul, 110-744

  • Study site

    Seoul, 120-752

  • Study site

    Seoul, 135-710

  • Study site

    Seoul, 137-701

Other trials in South Korea

Japan4 sites

  • Study site

    Kashiwa, Chiba, 277-8577

  • Study site

    Koto-ku, Tokyo, 135-8550

  • Study site

    Nagoya, Aichi-ken, 464-8681

  • Study site

    Nagoya, Aichi-ken, 466-8560

Other trials in Japan

Poland4 sites

  • Study site

    Gliwice, 44-101

  • Study site

    Poznan, 60-355

  • Study site

    Warsaw, 02-781

  • Study site

    Warsaw, 04-141

Other trials in Poland

Sweden4 sites

  • Study site

    Gothenburg, 413 45

  • Study site

    Linköping, 581 85

  • Study site

    Lund, 221 85

  • Study site

    Stockholm, 171 76

Other trials in Sweden

Netherlands2 sites

  • Study site

    Groningen, 9713 GZ

  • Study site

    Leiden, 2333 ZA

Other trials in Netherlands

Spain2 sites

  • Study site

    Barcelona, 08035

  • Study site

    Majadahonda, Madrid, 28222

Other trials in Spain

Austria1 site

  • Study site

    Vienna, 1090

Other trials in Austria

Belgium1 site

  • Study site

    Bruxelles - Brussel, 1000

Other trials in Belgium

Bulgaria1 site

  • Study site

    Sofia, 1527

Other trials in Bulgaria

Denmark1 site

  • Study site

    Odense C, 5000

Other trials in Denmark

Russia1 site

  • Study site

    Obninsk, 249036

Other trials in Russia

Saudi Arabia1 site

  • Study site

    Riyadh, 11211

Other trials in Saudi Arabia

About this study

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

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

Read the 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

Being tested
Sorafenib (Nexavar, BAY43-9006), Placebo
Keywords
RAI-Refractory, Differentiated, Follicular, Papillary, Hurthle
Medical subject headings
Thyroid Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sorafenib (Nexavar, BAY43-9006)Drug

    Sorafenib 400 mg will be administered orally, twice daily (approximately every 12 hours).

  • PlaceboDrug

    Placebo (2 tablets) will be administered orally, twice daily (approximately every 12 hours).

Study groups in NCT00984282
Study groupRoleWhat they receive
Sorafenib (Nexavar, BAY43-9006)ExperimentalParticipants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle
Receives: Drug: Sorafenib (Nexavar, BAY43-9006)
PlaceboPlacebo comparatorParticipants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation

    PFS=time from randomization to first observed disease progression (radiological according to central assessment or clinical due to bone irradiation, whichever is earlier), or death due to any cause, if death occurred before progression. Progression was assessed by RECIST criteria, version 1.0, modified for bone lesions. PFS for participants without disease progression or death at the time of analysis or unblinding were censored at the last date of tumor assessment before unblinding. Participants with no tumor evaluation after baseline were censored at Day 1. PD (Progression Disease)=At least a 20% increase in sum of longest diameters (LD) of measured lesions taking as reference the smallest sum LD on study since the treatment started or the appearance of 1 or more new lesions. New lesions also constituted PD. In exceptional circumstances, unequivocal progression of a nonmeasured lesion may have been accepted as evidence of disease progression in participants with measurable disease.

    Measured: Final analysis to be performed when approximately 267 progression-free survival events (centrally assessed) had occurred, study duration approximately three years

Secondary outcomes (7)

  1. Overall Survival (OS)

    Overall survival was defined as the time (days) from date of randomization to date of death due to any cause. Subjects still alive at the time of analysis were censored at their date of last contact. Since the median value could not be estimated due to censored data, the percentage of participants who died is presented.

    Measured: From randomization of the first subject until the database cut-off (30 AUG 2017), study duration approximately eight years

  2. Time to Progression (TTP) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation

    Time to progression was defined at the time (days) from randomization to progression (based on central assessment [radiological and clinical progression due to bone irradiation])

    Measured: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years

  3. Disease Control Rate (DCR) Based on Central Assessment

    Disease control rate was defined as the proportion of subjects whose best response was complete response (CR), partial response (PR), or stable disease (SD). Per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, CR and PR were to be confirmed by another scan at least 4 weeks later; SD had to be documented at least 4 weeks after date of randomization. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum. SD = steady state of disease which is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

    Measured: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years

  4. Response Rate Based on Central Assessment

    Response rate was defined as the proportion of subjects whose best response was CR or PR. Per RECIST, CR and PR was to be confirmed by another scan at least 4 weeks later. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum.

    Measured: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years

  5. Duration of Response (DOR) Based on Central Assessment

    Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum.

    Measured: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years

  6. Maximum Percent Reduction in Target Lesion Size Based on Central Assessment

    The magnitude of change from baseline in target lesion size in evaluable participants with scans was determined.

    Measured: From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years

  7. AUC(0-12h),ss (Area Under the Concentration Time Curve From Time 0 to 12 Hours at Steady State)

    Sorafenib AUC(0-12h),ss (area under the concentration time curve from time 0 to 12 hours at steady state) was estimated from the steady state plasma concentration.

    Measured: A single pharmacokinetic plasma sample was collected at steady state (after 14 days of uninterrupted, unmodified sorafenib dosing)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2009 (estimated)
  2. Study start15 Oct 2009
  3. Primary completion31 Aug 2012
  4. Study completion30 Aug 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
417 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00984282
Sponsor's protocol ID
14295
Other IDs
2009-012007-25, 2009
Status last verified
Aug 2018
First submitted
24 Sep 2009
Last updated
13 Sep 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 26370187

  • 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.

    PubMed 24768112

  • 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.

    PubMed 21834960

  • 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.

    PubMed 31558473

  • 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.

    PubMed 31540966

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sorafenib (Nexavar, BAY43-9006) in people with Thyroid Neoplasms, run by Bayer at 81 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 81 sites in United States, Italy, United Kingdom, China, France and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation (time frame: Final analysis to be performed when approximately 267 progression-free survival events (centrally assessed) had occurred, study duration approximately three years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00984282, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2018.

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