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

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ClinicalTrials.gov Identifier: NCT01321554
Recruitment Status : Completed
First Posted : March 23, 2011
Results First Posted : December 12, 2016
Last Update Posted : April 2, 2020
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Tracking Information
First Submitted Date  ICMJE March 10, 2011
First Posted Date  ICMJE March 23, 2011
Results First Submitted Date  ICMJE March 13, 2015
Results First Posted Date  ICMJE December 12, 2016
Last Update Posted Date April 2, 2020
Actual Study Start Date  ICMJE March 17, 2011
Actual Primary Completion Date November 15, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 22, 2011)
To compare the Progression-free Survival (PFS) of subjects with 131IRefractory differentiated thyroid cancer (DTC) with radiographic evidence of disease progression within the prior 12 months treated with E7080 versus Placebo. [ Time Frame: Date of randomization to the date of disease progression (measured every 8 weeks) or death (whichever occurs first) as determined by blinded independent imaging review ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2020)
  • 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.
  • 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.
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2011)
To compare Overall Response Rate (ORR) (Complete and Partial Responses, CR and PR) of subjects treated with E7080 versus Placebo. [ Time Frame: Date of randomization to the date of disease progression (measured every 8 weeks) or death ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer (DTC)
Official Title  ICMJE A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer
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).
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Thyroid Cancer
Intervention  ICMJE
  • Drug: Lenvatinib
    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 Name: Lenvatinib (Lenvima, E7080)
  • Drug: Placebo
    Matching placebo (two 10-mg and one 4-mg lenvatinib matched capsules) taken orally once daily, continuously.
  • Drug: Lenvatinib

    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 Name: Lenvatinib (Lenvima, E7080)
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Lenvatinib
  • 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.
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: Lenvatinib
  • 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.
    Intervention: Drug: Lenvatinib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 9, 2013)
392
Original Estimated Enrollment  ICMJE
 (submitted: March 22, 2011)
360
Actual Study Completion Date  ICMJE March 19, 2019
Actual Primary Completion Date November 15, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Chile,   Czechia,   Denmark,   France,   Germany,   Italy,   Japan,   Korea, Republic of,   Poland,   Portugal,   Romania,   Russian Federation,   Spain,   Sweden,   Thailand,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Switzerland
 
Administrative Information
NCT Number  ICMJE NCT01321554
Other Study ID Numbers  ICMJE E7080-G000-303
2010-023783-41 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eisai Inc.
Study Sponsor  ICMJE Eisai Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Eisai Inc.
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP