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

June 16, 2023 updated by: Eisai Inc.

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).

Study Overview

Status

Completed

Conditions

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.

Study Type

Interventional

Enrollment (Actual)

392

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Rosario, Argentina
        • Facility 1
      • San Salvador de Jujuy, Argentina
        • Facility 1
      • Tucuman, Argentina
        • Facility 1
      • Heidelberg, Australia
        • Facility 1
    • New South Wales
      • Saint Leonards, New South Wales, Australia
        • Facility 1
    • Queensland
      • Herston, Queensland, Australia
        • Facility 1
    • Tasmania
      • Hobart, Tasmania, Australia
        • Facility 1
    • Victoria
      • Melbourne, Victoria, Australia
        • Facility 1
      • Wien, Austria
        • Facility 1
      • Bruxelles, Belgium
        • Facility 1
      • Edegem, Belgium
        • Facility 1
      • Namur, Belgium
        • Facility 1
      • Brasilia, Brazil
        • Facility 1
      • Joinville, Brazil
        • Facility 1
      • Novo Hamburgo, Brazil
        • Facility 1
      • Rio de Janeiro, Brazil
        • Facility 1
      • Salvador, Brazil
        • Facility 1
      • Sao Paulo, Brazil
        • Facility 1
      • Sao Paulo, Brazil
        • Facility 2
      • Quebec, Canada
        • Facility 1
    • Ontario
      • London, Ontario, Canada
        • Facility 1
      • Toronto, Ontario, Canada
        • Facility 1
    • Quebec
      • Montreal, Quebec, Canada
        • Facility 1
      • Santiago, Chile
        • Facility 1
      • Santiago, Chile
        • Facility 2
      • Santiago, Chile
        • Facility 3
      • Temuco, Chile
        • Facility 1
      • Vina 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 1
      • Paris, France
        • Facility 2
      • Strasbourg, France
        • Facility 1
      • Vandoeuvre Les Nancy, France
        • Facility 1
      • Villejuif, France
        • Facility 1
      • Essen, Germany
        • Facility 1
      • Hannover, Germany
        • Facility 1
      • Leipzig, Germany
        • Facility 1
      • Mainz, Germany
        • Facility 1
      • Munchen, Germany
        • Facility 1
      • Tubingen, Germany
        • Facility 1
      • Wurzburg, Germany
        • Facility 1
      • Catania, Italy
        • Facility 1
      • Livorno, Italy
        • Facility 1
      • Milano, Italy
        • Facility 1
      • Milano, Italy
        • Facility 2
      • Milano, Italy
        • Facility 3
      • Milano, Italy
        • Facility 4
      • Milano, Italy
        • Facility 5
      • Monserrato, Italy
        • Facility 1
      • Napoli, Italy
        • Facility 1
      • Padova, Italy
        • Facility 1
      • Pisa, Italy
        • Facility 1
      • Roma, Italy
        • Facility 1
      • Roma, Italy
        • Facility 2
      • Rozzano, Italy
        • Facility 1
      • Torino, Italy
        • Facility 1
      • Viagrande, Italy
        • Facility 1
    • Aichi
      • Nagoya, Aichi, Japan
        • Eisai trial site 1
      • Nagoya, Aichi, Japan
        • Eisai trial site 2
    • Chiba
      • Kashiwa, Chiba, Japan
        • Eisai trial site 1
    • Fukui
      • Fukui-city, Fukui, Japan
        • Eisai trial site 1
    • Hyogo
      • Kobe-city, Hyogo, Japan
        • Eisai trial site 1
    • Tokyo
      • Koto-ku, Tokyo, Japan
        • Eisai trial site 1
      • Daejeon, Korea, Republic of
        • Facility 1
      • Gyeonggi-do, Korea, Republic of
        • Facility 1
      • Seoul, Korea, Republic of
        • Facility 1
      • Seoul, Korea, Republic of
        • Facility 2
      • Seoul, Korea, Republic of
        • Facility 3
      • Uijeongbu, Korea, Republic of
        • 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 1
      • Bucharest, Romania
        • Facility 2
      • Cluj-Napoca, Romania
        • Facility 1
      • Krasnodar, Russian Federation
        • Facility 1
      • Kursk, Russian Federation
        • Facility 1
      • Obninsk, Russian Federation
        • Facility 1
      • Ufa, Russian Federation
        • Facility 1
      • Barcelona, Spain
        • Facility 2
      • L'Hospitalet de Llobregat, Spain
        • Facility 1
      • Madrid, Spain
        • Facility 1
      • Madrid, Spain
        • Facility 2
      • Madrid, Spain
        • Facility 3
      • Madrid, Spain
        • Facility 4
      • Madrid, Spain
        • Facility 5
    • Andalucia
      • Malaga, Andalucia, Spain
        • Facility 2
    • Cataluna
      • Barcelona, Cataluna, Spain
        • Facility 1
    • Galicia
      • La Coruna, Galicia, Spain
        • Facility 1
      • Goteborg, Sweden
        • Facility 1
      • Lund, Sweden
        • Facility 1
      • Stockholm, Sweden
        • Facility 1
      • Bangkok, Thailand
        • Facility 1
      • Bangkok, Thailand
        • Facility 2
      • Chiang Mai, Thailand
        • Facility 1
      • Khon Kaen, Thailand
        • Facility 1
      • Pathumwan, Thailand
        • Facility 1
      • Aberdeen, United Kingdom
        • Facility 1
      • Glasgow, United Kingdom
        • Facility 1
      • London, United Kingdom
        • Facility 2
      • London, United Kingdom
        • Facility 3
      • Manchester, United Kingdom
        • Facility 1
      • Manchester, United Kingdom
        • Facility 2
      • Sheffield, United Kingdom
        • Facility 1
      • Sutton, United Kingdom
        • Facility 1
    • Arkansas
      • Little Rock, Arkansas, United States
        • Facility 1
    • California
      • 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 1
      • Orange, California, United States
        • Facility 2
      • Sacramento, California, United States
        • Facility 1
      • Torrance, California, United States
        • Facility 1
    • Colorado
      • Aurora, Colorado, United States
        • Facility 1
    • District of Columbia
      • Washington, District of Columbia, United States
        • Facility 1
    • Florida
      • Orlando, Florida, United States
        • Facility 1
      • Weston, Florida, United States
        • Facility 1
    • Illinois
      • Chicago, Illinois, United States
        • Facility 1
      • Chicago, Illinois, United States
        • Facility 2
    • Indiana
      • Indianapolis, Indiana, United States
        • Facility 1
    • Kentucky
      • Lexington, Kentucky, United States
        • Facility 1
    • Maryland
      • Baltimore, Maryland, United States
        • Facility 1
    • Michigan
      • Boston, Michigan, United States
        • Facility 1
      • Boston, Michigan, United States
        • Facility 2
      • Detroit, Michigan, United States
        • Facility 1
      • Lansing, Michigan, United States
        • Facility 1
    • Minnesota
      • Minneapolis, Minnesota, United States
        • Facility 1
    • Missouri
      • Columbia, Missouri, United States
        • Facility 1
    • Nebraska
      • Omaha, Nebraska, United States
        • Facility 1
    • New Hampshire
      • Lebanon, New Hampshire, United States
        • Facility 1
    • New Jersey
      • Morristown, New Jersey, United States
        • Facility 1
      • Neptune, New Jersey, United States
        • Facility 1
    • New York
      • Bronx, New York, United States
        • Facility 1
      • New York, New York, United States
        • Facility 1
      • New York, New York, United States
        • Facility 2
    • Ohio
      • Columbus, Ohio, United States
        • Facility 1
    • Oregon
      • Portland, Oregon, United States
        • Facility 1
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • Facility 1
      • Philadelphia, Pennsylvania, United States
        • Facility 2
    • Texas
      • Houston, Texas, United States
        • Facility 1
    • Washington
      • Seattle, Washington, United States
        • Facility 1
    • West Virginia
      • Morgantown, West Virginia, United States
        • Facility 1
    • Wisconsin
      • Milwaukee, Wisconsin, United States
        • Facility 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  1. Histologically or cytologically confirmed diagnosis of one of the following DTC subtypes: Papillary thyroid cancer (PTC) or follicular thyroid cancer (FTC).
  2. Measurable disease according to (RECIST 1.1) and confirmed by central radiographic review.
  3. 131 I-refractory/resistant disease.
  4. Evidence of disease progression within 12 months prior to signing informed consent (+1 month screening window).
  5. Prior treatment with 0 or 1 vascular endothelial growth-factor (VEGF) or vascular endothelial growth-factor receptors (VEGFR) targeted therapy.
  6. Adequate renal, liver, bone marrow, and blood coagulation function, as defined in the protocol.

Exclusion criteria:

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

Inclusion criteria for OOL Lenvatinib Treatment Period :

Participants were eligible for lenvatinib treatment in the OOL Lenvatinib Treatment Period if the met the following criteria:

  1. Placebo-treated participants in the Randomization Phase who had progressive disease (PD) confirmed by IIR, and who requested treatment with lenvatinib.
  2. Participants who continued to satisfy specified inclusion and exclusion criteria as presented in the study protocol.
  3. 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.
  4. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lenvatinib (Randomization Phase)
Participants 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 (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.
Other Names:
  • 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.

Other Names:
  • Lenvatinib (Lenvima, E7080)
Placebo Comparator: Placebo (Randomization Phase)
Participants 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.
Matching placebo (two 10-mg and one 4-mg lenvatinib matched capsules) taken orally once daily, continuously.
Experimental: Lenvatinib 24 mg (OOL Lenvatinib Treatment Period)
Participants 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 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.
Other Names:
  • 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.

Other Names:
  • Lenvatinib (Lenvima, E7080)
Experimental: Lenvatinib 20 mg (OOL Lenvatinib Treatment Period)
Participants 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.
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.
Other Names:
  • 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.

Other Names:
  • Lenvatinib (Lenvima, E7080)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
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
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.
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)
Time Frame: 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
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.
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
Time Frame: Cycle 1 Days 1 and 15: 0-10 hours postdose; Cycle 2 Day 1: 0-12 hour postdose
Cycle 1 Days 1 and 15: 0-10 hours postdose; Cycle 2 Day 1: 0-12 hour postdose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 17, 2011

Primary Completion (Actual)

November 15, 2013

Study Completion (Actual)

March 19, 2019

Study Registration Dates

First Submitted

March 10, 2011

First Submitted That Met QC Criteria

March 22, 2011

First Posted (Estimated)

March 23, 2011

Study Record Updates

Last Update Posted (Actual)

June 22, 2023

Last Update Submitted That Met QC Criteria

June 16, 2023

Last Verified

March 1, 2020

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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