A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer (DTC)
SELECT
2 other identifiers
interventional
392
22 countries
154
Brief 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. 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2011
Longer than P75 for phase_3
154 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 10, 2011
CompletedStudy Start
First participant enrolled
March 17, 2011
CompletedFirst Posted
Study publicly available on registry
March 23, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 15, 2013
CompletedResults Posted
Study results publicly available
December 12, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
March 19, 2019
CompletedJune 22, 2023
March 1, 2020
2.7 years
March 10, 2011
March 13, 2015
June 16, 2023
Conditions
Outcome Measures
Primary Outcomes (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.
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)
Overall Response Rate (ORR)
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
Overall Survival (OS)
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
Pharmacokinetic (PK) Profile of Lenvatinib: Area Under the Plasma Concentration Curve
Cycle 1 Days 1 and 15: 0-10 hours postdose; Cycle 2 Day 1: 0-12 hour postdose
Study Arms (4)
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.
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.
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.
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.
Interventions
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.
Matching placebo (two 10-mg and one 4-mg lenvatinib matched capsules) taken orally once daily, continuously.
Eligibility Criteria
You may qualify if:
- 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.
- 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.
You may not qualify if:
- Anaplastic or medullary carcinoma of the thyroid
- 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.
- 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 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eisai Inc.lead
Study Sites (155)
Facility 1
Little Rock, Arkansas, United States
Facility 1
La Jolla, California, United States
Facility 1
Los Gatos, California, United States
Facility 1
Mission Viejo, California, United States
Facility 1
Orange, California, United States
Facility 2
Orange, California, United States
Facility 1
Sacramento, California, United States
Facility 1
Torrance, California, United States
Facility 1
Aurora, Colorado, United States
Facility 1
Washington D.C., District of Columbia, United States
Facility 1
Orlando, Florida, United States
Facility 1
Weston, Florida, United States
Facility 1
Chicago, Illinois, United States
Facility 2
Chicago, Illinois, United States
Facility 1
Indianapolis, Indiana, United States
Facility 1
Lexington, Kentucky, United States
Facility 1
Baltimore, Maryland, United States
Facility 1
Boston, Michigan, United States
Facility 2
Boston, Michigan, United States
Facility 1
Detroit, Michigan, United States
Facility 1
Lansing, Michigan, United States
Facility 1
Minneapolis, Minnesota, United States
Facility 1
Columbia, Missouri, United States
Facility 1
Omaha, Nebraska, United States
Facility 1
Lebanon, New Hampshire, United States
Facility 1
Morristown, New Jersey, United States
Facility 1
Neptune City, New Jersey, United States
Facility 1
New York, New York, United States
Facility 2
New York, New York, United States
Facility 1
The Bronx, New York, United States
Facility 1
Columbus, Ohio, United States
Facility 1
Portland, Oregon, United States
Facility 1
Philadelphia, Pennsylvania, United States
Facility 2
Philadelphia, Pennsylvania, United States
Facility 1
Houston, Texas, United States
Facility 1
Seattle, Washington, United States
Facility 1
Morgantown, West Virginia, United States
Facility 1
Milwaukee, Wisconsin, United States
Facility 1
Rosario, Argentina
Facility 1
San Miguel de Tucumán, Argentina
Facility 1
San Salvador de Jujuy, Argentina
Facility 1
Saint Leonards, New South Wales, Australia
Facility 1
Herston, Queensland, Australia
Facility 1
Hobart, Tasmania, Australia
Facility 1
Melbourne, Victoria, Australia
Facility 1
Heidelberg, Australia
Facility 1
Vienna, Austria
Facility 1
Brussels, Belgium
Facility 1
Edegem, Belgium
Facility 1
Namur, Belgium
Facility 1
Brasília, Brazil
Facility 1
Joinville, Brazil
Facility 1
Novo Hamburgo, Brazil
Facility 1
Rio de Janeiro, Brazil
Facility 1
Salvador, Brazil
Facility 1
São Paulo, Brazil
Facility 2
São Paulo, Brazil
Facility 1
London, Ontario, Canada
Facility 1
Toronto, Ontario, Canada
Facility 1
Montreal, Quebec, Canada
Facility 1
Québec, Canada
Facility 1
Santiago, Chile
Facility 2
Santiago, Chile
Facility 3
Santiago, Chile
Facility 1
Temuco, Chile
Facility 1
Viña del Mar, Chile
Facility 1
Olomouc, Czechia
Facility 1
Odense, Denmark
Facility 1
Angers, France
Facility 1
Bordeaux, France
Facility 1
Caen, France
Facility 1
Clermont-Ferrand, France
Facility 1
Dijon, France
Facility 1
Lille, France
Facility 1
Lyon, France
Facility 1
Marseille, France
Facility 1
Nice, France
Facility 1
Paris, France
Facility 2
Paris, France
Facility 1
Strasbourg, France
Facility 1
Vandœuvre-lès-Nancy, France
Facility 1
Villejuif, France
Facility 1
Essen, Germany
Facility 1
Hanover, Germany
Facility 1
Leipzig, Germany
Facility 1
Mainz, Germany
Facility 1
München, Germany
Facility 1
Tübingen, Germany
Facility 1
Würzburg, Germany
Facility 1
Catania, Italy
Facility 1
Livorno, Italy
Facility 1
Milan, Italy
Facility 2
Milan, Italy
Facility 3
Milan, Italy
Facility 4
Milan, Italy
Facility 5
Milan, Italy
Facility 1
Monserrato, Italy
Facility 1
Napoli, Italy
Facility 1
Padua, Italy
Facility 1
Pisa, Italy
Facility 1
Roma, Italy
Facility 2
Roma, Italy
Facility 1
Rozzano, Italy
Facility 1
Torino, Italy
Facility 1
Viagrande, Italy
Eisai Trial Site 1
Nagoya, Aichi-ken, Japan
Eisai Trial Site 2
Nagoya, Aichi-ken, Japan
Eisai Trial Site 1
Kashiwa, Chiba, Japan
Eisai Trial Site 1
Fukui-shi, Fukui, Japan
Eisai Trial Site 1
Kobe, Hyōgo, Japan
Eisai Trial Site 1
Koto-ku, Tokyo, Japan
Facility 1
Gliwice, Poland
Facility 1
Kielce, Poland
Facility 1
Poznan, Poland
Facility 1
Lisbon, Portugal
Facility 1
Porto, Portugal
Facility 1
Bucharest, Romania
Facility 2
Bucharest, Romania
Facility 1
Cluj-Napoca, Romania
Facility 1
Krasnodar, Russia
Facility 1
Kursk, Russia
Facility 1
Obninsk, Russia
Facility 1
Ufa, Russia
Facility 1
Daejeon, South Korea
Facility 1
Gyeonggi-do, South Korea
Facility 1
Seoul, South Korea
Facility 2
Seoul, South Korea
Facility 3
Seoul, South Korea
Facility 1
Uijeongbu-si, South Korea
Facility 2
Málaga, Andalusia, Spain
Facility 1
Barcelona, Catalonia, Spain
Facility 1
A Coruña, Galicia, Spain
Facility 2
Barcelona, Spain
Facility 1
L'Hospitalet de Llobregat, Spain
Facility 1
Madrid, Spain
Facility 2
Madrid, Spain
Facility 3
Madrid, Spain
Facility 4
Madrid, Spain
Facility 5
Madrid, Spain
Facility 1
Gothenburg, Sweden
Facility 1
Lund, Sweden
Facility 1
Stockholm, Sweden
Facility 1
Bangkok, Thailand
Facility 2
Bangkok, Thailand
Facility 1
Chiang Mai, Thailand
Facility 1
Khon Kaen, Thailand
Facility 1
Pathumwan, Thailand
Facility 1
Aberdeen, United Kingdom
Facility 1
Glasgow, United Kingdom
Facility 2
London, United Kingdom
Facility 3
London, United Kingdom
Facility 1
Manchester, United Kingdom
Facility 2
Manchester, United Kingdom
Facility 1
Sheffield, United Kingdom
Facility 1
Sutton, United Kingdom
Related Publications (7)
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.
PMID: 33637020DERIVEDTahara 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.
PMID: 33611104DERIVEDTahara 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.
PMID: 30471649DERIVEDTahara 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.
PMID: 28237867DERIVEDRobinson 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.
PMID: 27548104DERIVEDKiyota 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.
PMID: 26426092DERIVEDSchlumberger 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.
PMID: 25671254DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Eisai Medical Information
- Organization
- Eisai, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 10, 2011
First Posted
March 23, 2011
Study Start
March 17, 2011
Primary Completion
November 15, 2013
Study Completion
March 19, 2019
Last Updated
June 22, 2023
Results First Posted
December 12, 2016
Record last verified: 2020-03