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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01321554




Registration number
NCT01321554
Ethics application status
Date submitted
10/03/2011
Date registered
23/03/2011
Date last updated
2/04/2020

Titles & IDs
Public title
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer (DTC)
Scientific title
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer
Secondary ID [1] 0 0
2010-023783-41
Secondary ID [2] 0 0
E7080-G000-303
Universal Trial Number (UTN)
Trial acronym
SELECT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Thyroid Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Thyroid
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lenvatinib
Treatment: Drugs - Placebo
Treatment: Drugs - Lenvatinib

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.

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.

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.

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.


Treatment: Drugs: 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.

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

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
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 [1] 0 0
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.
Timepoint [1] 0 0
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 [2] 0 0
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.
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Pharmacokinetic (PK) Profile of Lenvatinib: Area Under the Plasma Concentration Curve
Timepoint [3] 0 0
Cycle 1 Days 1 and 15: 0-10 hours postdose; Cycle 2 Day 1: 0-12 hour postdose

Eligibility
Key inclusion criteria
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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC
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- Saint Leonards
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- Herston
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- Hobart
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- Melbourne
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- Heidelberg
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Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eisai Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/show/NCT01321554
Trial related presentations / publications
Public notes

Contacts
Principal investigator
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Address 0 0
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Email 0 0
Contact person for public queries
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Contact person for scientific queries

Summary results
Other publications