AzTrials
AzTrials

Thyroid CancerPhase 3SELECTNCT01321554

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer (DTC)

A Phase 3 study testing Lenvatinib in people with Thyroid Cancer, run by Eisai Inc. at 155 sites in 23 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

This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study to compare the progression free survival, overall response rate (ORR) and safety of participants treated with lenvatinib 24 mg by continuous once daily oral dosing versus placebo. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Thyroid Cancer
What is being tested?
Lenvatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
392 participants
Where
155 sitesin 23 countries
Study dates
17 Mar 2011to 19 Mar 2019
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

  • Histologically or cytologically confirmed diagnosis of one of the following DTC subtypes: Papillary thyroid cancer (PTC) or follicular thyroid cancer (FTC).
  • Measurable disease according to (RECIST 1.1) and confirmed by central radiographic review.
  • 131 I-refractory/resistant disease.
  • Evidence of disease progression within 12 months prior to signing informed consent (+1 month screening window).
  • Prior treatment with 0 or 1 vascular endothelial growth-factor (VEGF) or vascular endothelial growth-factor receptors (VEGFR) targeted therapy.
  • Adequate renal, liver, bone marrow, and blood coagulation function, as defined in the protocol.
Show all 11Show fewer
  • Participants were eligible for lenvatinib treatment in the OOL Lenvatinib Treatment Period if the met the following criteria:
  • Placebo-treated participants in the Randomization Phase who had progressive disease (PD) confirmed by IIR, and who requested treatment with lenvatinib.
  • Participants who continued to satisfy specified inclusion and exclusion criteria as presented in the study protocol.
  • Participants with maximum interval between the day of confirmation of PD by IIR and Cycle 1/Day 1 of the OOL Lenvatinib Treatment Period of less than or equal to 3 months.
  • No systemic anticancer treatment during the interval between the day of confirmation of PD by the IIR and Cycle 1/Day 1 of the OOL Lenvatinib Treatment Period.

Who cannot join

  • Anaplastic or medullary carcinoma of the thyroid
  • 2 or more prior VEGF/ VEGFR-targeted therapies
  • Received any anticancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug.

Trial locations and contacts

155 sites in 23 countries.

155 sites in 23 countries

United States38 sites

  • Facility 1

    Aurora, Colorado

  • Facility 1

    Baltimore, Maryland

  • Facility 1

    Boston, Michigan

  • Facility 2

    Boston, Michigan

  • Facility 1

    Chicago, Illinois

  • Facility 2

    Chicago, Illinois

  • Facility 1

    Columbia, Missouri

  • Facility 1

    Columbus, Ohio

  • Facility 1

    Detroit, Michigan

  • Facility 1

    Houston, Texas

  • Facility 1

    Indianapolis, Indiana

  • Facility 1

    La Jolla, California

  • Facility 1

    Lansing, Michigan

  • Facility 1

    Lebanon, New Hampshire

  • Facility 1

    Lexington, Kentucky

  • Facility 1

    Little Rock, Arkansas

  • Facility 1

    Los Gatos, California

  • Facility 1

    Milwaukee, Wisconsin

  • Facility 1

    Minneapolis, Minnesota

  • Facility 1

    Mission Viejo, California

  • Facility 1

    Morgantown, West Virginia

  • Facility 1

    Morristown, New Jersey

  • Facility 1

    Neptune City, New Jersey

  • Facility 1

    New York, New York

  • Facility 2

    New York, New York

  • Facility 1

    Omaha, Nebraska

  • Facility 1

    Orange, California

  • Facility 2

    Orange, California

  • Facility 1

    Orlando, Florida

  • Facility 1

    Philadelphia, Pennsylvania

  • Facility 2

    Philadelphia, Pennsylvania

  • Facility 1

    Portland, Oregon

  • Facility 1

    Sacramento, California

  • Facility 1

    Seattle, Washington

  • Facility 1

    The Bronx, New York

  • Facility 1

    Torrance, California

  • Facility 1

    Washington D.C., District of Columbia

  • Facility 1

    Weston, Florida

Other trials in United States

Italy16 sites

  • Facility 1

    Catania

  • Facility 1

    Livorno

  • Facility 1

    Milan

  • Facility 2

    Milan

  • Facility 3

    Milan

  • Facility 4

    Milan

  • Facility 5

    Milan

  • Facility 1

    Monserrato

  • Facility 1

    Naples

  • Facility 1

    Padova

  • Facility 1

    Pisa

  • Facility 1

    Roma

  • Facility 2

    Roma

  • Facility 1

    Rozzano

  • Facility 1

    Torino

  • Facility 1

    Viagrande

Other trials in Italy

France14 sites

  • Facility 1

    Angers

  • Facility 1

    Bordeaux

  • Facility 1

    Caen

  • Facility 1

    Clermont-Ferrand

  • Facility 1

    Dijon

  • Facility 1

    Lille

  • Facility 1

    Lyon

  • Facility 1

    Marseille

  • Facility 1

    Nice

  • Facility 1

    Paris

  • Facility 2

    Paris

  • Facility 1

    Strasbourg

  • Facility 1

    Vandœuvre-lès-Nancy

  • Facility 1

    Villejuif

Other trials in France

Spain10 sites

  • Facility 1

    A Coruña, Galicia

  • Facility 1

    Barcelona, Catalonia

  • Facility 2

    Barcelona

  • Facility 1

    L'Hospitalet de Llobregat

  • Facility 1

    Madrid

  • Facility 2

    Madrid

  • Facility 3

    Madrid

  • Facility 4

    Madrid

  • Facility 5

    Madrid

  • Facility 2

    Málaga, Andalusia

Other trials in Spain

United Kingdom8 sites

  • Facility 1

    Aberdeen

  • Facility 1

    Glasgow

  • Facility 2

    London

  • Facility 3

    London

  • Facility 1

    Manchester

  • Facility 2

    Manchester

  • Facility 1

    Sheffield

  • Facility 1

    Sutton

Other trials in United Kingdom

Brazil7 sites

  • Facility 1

    Brasília

  • Facility 1

    Joinville

  • Facility 1

    Novo Hamburgo

  • Facility 1

    Rio de Janeiro

  • Facility 1

    Salvador

  • Facility 1

    São Paulo

  • Facility 2

    São Paulo

Other trials in Brazil

Germany7 sites

  • Facility 1

    Essen

  • Facility 1

    Hanover

  • Facility 1

    Leipzig

  • Facility 1

    Mainz

  • Facility 1

    München

  • Facility 1

    Tübingen

  • Facility 1

    Würzburg

Other trials in Germany

Japan6 sites

  • Eisai Trial Site 1

    Fukui-shi, Fukui

  • Eisai Trial Site 1

    Kashiwa, Chiba

  • Eisai Trial Site 1

    Kobe, Hyōgo

  • Eisai Trial Site 1

    Koto-ku, Tokyo

  • Eisai Trial Site 1

    Nagoya, Aichi-ken

  • Eisai Trial Site 2

    Nagoya, Aichi-ken

Other trials in Japan

South Korea6 sites

  • Facility 1

    Daejeon

  • Facility 1

    Gyeonggi-do

  • Facility 1

    Seoul

  • Facility 2

    Seoul

  • Facility 3

    Seoul

  • Facility 1

    Uijeongbu-si

Other trials in South Korea

Australia5 sites

  • Facility 1

    Heidelberg

  • Facility 1

    Herston, Queensland

  • Facility 1

    Hobart, Tasmania

  • Facility 1

    Melbourne, Victoria

  • Facility 1

    Saint Leonards, New South Wales

Other trials in Australia

Chile5 sites

  • Facility 1

    Santiago

  • Facility 2

    Santiago

  • Facility 3

    Santiago

  • Facility 1

    Temuco

  • Facility 1

    Viña del Mar

Other trials in Chile

Thailand5 sites

  • Facility 1

    Bangkok

  • Facility 2

    Bangkok

  • Facility 1

    Chiang Mai

  • Facility 1

    Khon Kaen

  • Facility 1

    Pathumwan

Other trials in Thailand

Canada4 sites

  • Facility 1

    London, Ontario

  • Facility 1

    Montreal, Quebec

  • Facility 1

    Québec

  • Facility 1

    Toronto, Ontario

Other trials in Canada

Russia4 sites

  • Facility 1

    Krasnodar

  • Facility 1

    Kursk

  • Facility 1

    Obninsk

  • Facility 1

    Ufa

Other trials in Russia

Argentina3 sites

  • Facility 1

    Rosario

  • Facility 1

    San Miguel de Tucumán

  • Facility 1

    San Salvador de Jujuy

Other trials in Argentina

Belgium3 sites

  • Facility 1

    Brussels

  • Facility 1

    Edegem

  • Facility 1

    Namur

Other trials in Belgium

Poland3 sites

  • Facility 1

    Gliwice

  • Facility 1

    Kielce

  • Facility 1

    Poznan

Other trials in Poland

Romania3 sites

  • Facility 1

    Bucharest

  • Facility 2

    Bucharest

  • Facility 1

    Cluj-Napoca

Other trials in Romania

Sweden3 sites

  • Facility 1

    Gothenburg

  • Facility 1

    Lund

  • Facility 1

    Stockholm

Other trials in Sweden

Portugal2 sites

  • Facility 1

    Lisbon

  • Facility 1

    Porto

Other trials in Portugal

Austria1 site

  • Facility 1

    Vienna

Other trials in Austria

Czechia1 site

  • Facility 1

    Olomouc

Other trials in Czechia

Denmark1 site

  • Facility 1

    Odense

Other trials in Denmark

About this study

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer

This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study to compare the progression free survival, overall response rate (ORR) and safety of participants treated with lenvatinib 24 mg by continuous once daily oral dosing versus placebo. The study is conducted in 3 phases: a Prerandomization Phase (screening and baseline period), a Randomization Phase (double-blind treatment period), and an Extension Phase (Optional Open Label (OOL) Lenvatinib Treatment Period and a follow-up period).

Read the detailed description

Randomization Phase: Participants will receive blinded study drug (lenvatinib/placebo) in 2:1 ratio until documentation of disease progression (confirmed by independent imaging review), development of unacceptable toxicity, or withdrawal of consent. After having completed the primary analysis, subjects treated with lenvatinib who have not experienced disease progression may request to continue open label lenvatinib at the same dose, according to the clinical judgment of the investigator. Participants who discontinue treatment for any reason other than disease progression will be followed in the Randomization Phase until disease progression or start of another anticancer treatment; these participants then enter the Extension Phase for survival follow-up. Extension Phase: Participants in the placebo arm who have disease progression confirmed by IIR could request to enter the OOL Lenvatinib Treatment Period and receive lenvatinib treatment. Participants will receive lenvatinib treatment until disease progression (investigator's assessment), development of intolerable toxicity, or withdrawal of consent. Participants who had disease progression during the Randomization Phase and did not enter the OOL Lenvatinib Treatment Period and all participants who discontinued lenvatinib treatment in the OOL Lenvatinib Treatment Period will enter the follow-up period. Participants will be followed for survival, and all anticancer treatments will be recorded until the time of death.

Conditions
Thyroid Cancer
Being tested
Lenvatinib, Placebo
Medical subject headings
Thyroid Neoplasms

What participants receive

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

  • LenvatinibDrug

    Also called Lenvatinib (Lenvima, E7080)

    Lenvatinib 24 mg (two 10-mg and one 4-mg lenvatinib matched capsules) taken orally once daily, continuously. Dose interruptions or reductions were allowed for subjects who experienced treatment-related toxicity.

  • PlaceboDrug

    Matching placebo (two 10-mg and one 4-mg lenvatinib matched capsules) taken orally once daily, continuously.

  • LenvatinibDrug

    Also called Lenvatinib (Lenvima, E7080)

    Lenvatinib 20 mg (two 10-mg capsules) taken orally once daily, continuously. Dose interruptions or reductions were allowed for subjects who experienced treatment-related toxicity.

    The dose of lenvatinib during the OOL Lenvatinib Treatment Period was 24 mg once daily from 03 Oct 2011 until 15 Feb 2013. The dose was lowered at the request of the Data Monitoring Committee to 20 mg on 16 Feb 2013. Thus, more subjects were treated with 24 mg starting dose and the treatment duration was longer for these participants than those whose starting dose was 20 mg.

Study groups in NCT01321554
Study groupRoleWhat they receive
Lenvatinib (Randomization Phase)ExperimentalParticipants randomly assigned in a 2:1 ratio to receive blinded study drug (lenvatinib or matching placebo) until documentation of disease progression (confirmed by IIR), development of unacceptable toxicity, or withdrawal of consent.
Receives: Drug: Lenvatinib
Placebo (Randomization Phase)Placebo comparatorParticipants randomly assigned in a 2:1 ratio to receive blinded study drug (lenvatinib or matching placebo) until documentation of disease progression (confirmed by IIR), development of unacceptable toxicity, or withdrawal of consent.
Receives: Drug: Placebo
Lenvatinib 24 mg (OOL Lenvatinib Treatment Period)ExperimentalParticipants will receive lenvatinib 24 mg, orally once daily until documentation of disease progression (confirmed by investigator's assessment), development of unacceptable toxicity, or withdrawal of consent. Placebo treated participants in the Randomization Phase who have progressive disease confirmed by IIR could request to receive lenvatinib treatment in the OOL Treatment Period.
Receives: Drug: Lenvatinib
Lenvatinib 20 mg (OOL Lenvatinib Treatment Period)ExperimentalParticipants will receive lenvatinib 20 mg, orally once daily until documentation of disease progression (confirmed by investigator's assessment), development of unacceptable toxicity, or withdrawal of consent. Placebo treated participants in the Randomization Phase who have progressive disease confirmed by IIR could request to receive lenvatinib treatment in the OOL Treatment Period.
Receives: Drug: Lenvatinib

What is being measured

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

  1. Progression Free Survival (PFS)

    PFS was defined as the time from the date of randomization to the date of first documentation of disease progression or death (whichever occurred first), as determined by blinded IIR using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for the double-blind treatment period (Randomization Phase). Disease progression per RECIST v1.1 was defined as at least a 20 percent (%) relative increase and 5 millimeter (mm) absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), recorded since the treatment started or the appearance of 1 or more new lesions.

    Measured: Date of randomization to the date of disease progression or death (whichever occurred first), assessed up to data cutoff date (15 Nov 2013) or up to approximately 2.5 years

Secondary outcomes (3)

  1. Overall Response Rate (ORR)

    ORR, defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) as determined by blinded IIR using RECIST 1.1 for target lesions and assessed by magnetic resonance imaging/computed tomography (MRI/CT) scans (for double blind treatment period i.e. Randomization Phase). CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR.

    Measured: Date of randomization to the date of disease progression or death (whichever occurred first), assessed up to data cutoff date (15 Nov 2013) or up to approximately 2.5 years

  2. Overall Survival (OS)

    Overall survival measured from the date of randomization until date of death from any cause. Overall survival is adjusted with rank preserving structural failure time.

    Measured: Date of randomization until date of death from any cause, assessed up to data cutoff date (15 Nov 2013) or up to approximately 2.5 years

  3. Pharmacokinetic (PK) Profile of Lenvatinib: Area Under the Plasma Concentration Curve

    Measured: Cycle 1 Days 1 and 15: 0-10 hours postdose; Cycle 2 Day 1: 0-12 hour postdose

Timeline

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

  1. First posted23 Mar 2011 (estimated)
  2. Study start17 Mar 2011
  3. Primary completion15 Nov 2013
  4. Study completion19 Mar 2019

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
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
392 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01321554
Sponsor's protocol ID
E7080-G000-303
Other IDs
2010-023783-41
Acronym
SELECT
Status last verified
Mar 2020
First submitted
10 Mar 2011
Last updated
22 Jun 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes

Publications

  • Taylor MH, Takahashi S, Capdevila J, Tahara M, Leboulleux S, Kiyota N, Dutcus CE, Xie R, Robinson B, Sherman S, Habra MA, Elisei R, Wirth LJ. Correlation of Performance Status and Neutrophil-Lymphocyte Ratio with Efficacy in Radioiodine-Refractory Differentiated Thyroid Cancer Treated with Lenvatinib. Thyroid. 2021 Aug;31(8):1226-1234. doi: 10.1089/thy.2020.0779. Epub 2021 Apr 29.

    PubMed 33637020

  • Tahara M, Kiyota N, Hoff AO, Badiu C, Owonikoko TK, Dutcus CE, Suzuki T, Ren M, Wirth LJ. Impact of lung metastases on overall survival in the phase 3 SELECT study of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer. Eur J Cancer. 2021 Apr;147:51-57. doi: 10.1016/j.ejca.2020.12.032. Epub 2021 Feb 19.

    PubMed 33611104

  • Tahara M, Brose MS, Wirth LJ, Suzuki T, Miyagishi H, Fujino K, Dutcus CE, Gianoukakis A. Impact of dose interruption on the efficacy of lenvatinib in a phase 3 study in patients with radioiodine-refractory differentiated thyroid cancer. Eur J Cancer. 2019 Jan;106:61-68. doi: 10.1016/j.ejca.2018.10.002. Epub 2018 Nov 22.

    PubMed 30471649

  • Tahara M, Schlumberger M, Elisei R, Habra MA, Kiyota N, Paschke R, Dutcus CE, Hihara T, McGrath S, Matijevic M, Kadowaki T, Funahashi Y, Sherman SI. Exploratory analysis of biomarkers associated with clinical outcomes from the study of lenvatinib in differentiated cancer of the thyroid. Eur J Cancer. 2017 Apr;75:213-221. doi: 10.1016/j.ejca.2017.01.013. Epub 2017 Feb 24.

    PubMed 28237867

  • Robinson B, Schlumberger M, Wirth LJ, Dutcus CE, Song J, Taylor MH, Kim SB, Krzyzanowska MK, Capdevila J, Sherman SI, Tahara M. Characterization of Tumor Size Changes Over Time From the Phase 3 Study of Lenvatinib in Thyroid Cancer. J Clin Endocrinol Metab. 2016 Nov;101(11):4103-4109. doi: 10.1210/jc.2015-3989. Epub 2016 Aug 22.

    PubMed 27548104

  • Kiyota N, Schlumberger M, Muro K, Ando Y, Takahashi S, Kawai Y, Wirth L, Robinson B, Sherman S, Suzuki T, Fujino K, Gupta A, Hayato S, Tahara M. Subgroup analysis of Japanese patients in a phase 3 study of lenvatinib in radioiodine-refractory differentiated thyroid cancer. Cancer Sci. 2015 Dec;106(12):1714-21. doi: 10.1111/cas.12826. Epub 2015 Nov 2.

    PubMed 26426092

  • Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, Habra MA, Newbold K, Shah MH, Hoff AO, Gianoukakis AG, Kiyota N, Taylor MH, Kim SB, Krzyzanowska MK, Dutcus CE, de las Heras B, Zhu J, Sherman SI. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015 Feb 12;372(7):621-30. doi: 10.1056/NEJMoa1406470.

    PubMed 25671254

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lenvatinib in people with Thyroid Cancer, run by Eisai Inc. at 155 sites in 23 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 11 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 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 155 sites in United States, Italy, France, Spain, United Kingdom and 18 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 12 Dec 2016). 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) (time frame: Date of randomization to the date of disease progression or death (whichever occurred first), assessed up to data cutoff date (15 Nov 2013) or up to approximately 2.5 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 NCT01321554, which also lists 7 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 22 Jun 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in