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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00784303




Registration number
NCT00784303
Ethics application status
Date submitted
30/10/2008
Date registered
2/11/2008
Date last updated
22/04/2020

Titles & IDs
Public title
Evaluating the Safety and Efficacy of Oral Lenvatinib in Medullary and Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers, Stratified by Histology
Scientific title
Phase II, Multicenter, Open-label, Single Arm Trial to Evaluate the Safety and Efficacy of Oral E7080 in Medullary and Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers, Stratified by Histology
Secondary ID [1] 0 0
E7080-G000-201
Universal Trial Number (UTN)
Trial acronym
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 (DTC Cohort)
Treatment: Drugs - Lenvatinib (MTC Cohort)

Experimental: DTC cohort - This arm will enroll participants with radioiodine (131 I)-refractory/resistant differentiated thyroid cancer.

Experimental: MTC cohort - This arm will enroll participants with medullary thyroid cancer.


Treatment: Drugs: Lenvatinib (DTC Cohort)
24 mg lenvatinib (two 10 mg tablets and one 4 mg tablet) given orally, once daily, or 10 mg lenvatinib orally twice daily (20 mg total). Out of 58 participants in the DTC cohort, 56 participants received 24 mg lenvatinib once daily and 2 participants received 10 mg lenvatinib twice daily (total 20 mg daily), given continuously in 28-day treatment cycles.

Treatment: Drugs: Lenvatinib (MTC Cohort)
24 mg lenvatinib (two 10 mg tablets and one 4 mg tablet) given orally, once daily given continuously in 28-day treatment cycles.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date 11 April 2011, for up to approximately 2 years 5 months
Primary outcome [2] 0 0
Plasma Pharmacokinetics (PK): Steady State Area Under the Plasma Concentration Curve (AUC)
Timepoint [2] 0 0
Cycle 1 Day 1 (predose and at 0.5 and 2 hours postdose), Cycle 1 Day 8 (predose), Cycle 2 Day 1 (predose and at 0.5 and 2 hours postdose), and Cycle 3 Day 1 (predose and at 2 hours postdose) (Cycle length= 28 days)
Secondary outcome [1] 0 0
Change From Baseline in Free Thyroxine (T4)
Timepoint [1] 0 0
Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 20, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days)
Secondary outcome [2] 0 0
Change From Baseline in Free Thyroid Stimulating Hormone (TSH)
Timepoint [2] 0 0
Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 20, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days)
Secondary outcome [3] 0 0
Percent Change From Baseline in Concentrations of Thyroglobulin (DTC Only)
Timepoint [3] 0 0
Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 19, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days)
Secondary outcome [4] 0 0
Percent Change From Baseline in Concentrations of Calcitonin (MTC Only)
Timepoint [4] 0 0
Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 20, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days)
Secondary outcome [5] 0 0
Percent Change From Baseline in Concentrations of Carcinoembryonic Antigen (CEA) (MTC Only)
Timepoint [5] 0 0
Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 20, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days)
Secondary outcome [6] 0 0
Change From Baseline in Concentrations of Cytochrome C (CytoC)
Timepoint [6] 0 0
Cycle 1 (Day 8), Cycle 2 (Days 1, 8 and 15), Cycles 3, 4, 5, 6, 7, 8, 9, 11, & 13 (Day 1), and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days)
Secondary outcome [7] 0 0
Change From Baseline in Concentrations of M-30 Neo-Antigen
Timepoint [7] 0 0
Cycle 1 (Day 8), Cycle 2 (Days 1, 8 & 15), Cycles 3, 4, 5, 6, 7, 8, 9, 11 & 13 (Day 1) and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days)
Secondary outcome [8] 0 0
Change From Baseline in Concentrations of Activated Caspase 3/7 (Casp 3/7)
Timepoint [8] 0 0
Cycle 1 (Day 8), Cycle 2 (Days 1, 8, & 15), Cycles 3, 4, 5, 6, 7, 8, 9, 11, & 13 (Day 1) and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days)
Secondary outcome [9] 0 0
Duration of Response (DoR) Assessed as Per Independent Imaging Reviewers (IIR)
Timepoint [9] 0 0
From date of the first CR or PR until the date of first documentation of disease progression or date of death, assessed up to data cutoff date 11 April 2011
Secondary outcome [10] 0 0
Disease Control Rate (DCR) Assessed as Per IIR
Timepoint [10] 0 0
From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date 11 April 2011, for up to approximately 2 years 5 months
Secondary outcome [11] 0 0
Clinical Benefit Rate (CBR) Assessed as Per IIR
Timepoint [11] 0 0
From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date 11 April 2011, for up to approximately 2 years 5 months
Secondary outcome [12] 0 0
Time to Response (TTR) Assessed as Per IIR
Timepoint [12] 0 0
From date of treatment start until date of first CR or PR, assessed up to data cutoff date 11 April 2011
Secondary outcome [13] 0 0
Progression Free Survival (PFS) Assessed as Per IIR
Timepoint [13] 0 0
From date of treatment start until date of progressive disease or death from any cause, assessed up to data cutoff date 11 April 2011, for up to approximately 2 years 5 months
Secondary outcome [14] 0 0
Overall Survival (OS)
Timepoint [14] 0 0
From date of treatment start until date of death from any cause, assessed up to data cutoff date 11 April 2011, for up to approximately 2 years 5 months
Secondary outcome [15] 0 0
Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib
Timepoint [15] 0 0
For each participant, from the first dose till 30 days after the last dose of study treatment (up to approximately 10 years 4 months)

Eligibility
Key inclusion criteria
Inclusion criteria:

1. Histologically or cytologically confirmed diagnosis of medullary thyroid cancer (MTC) or differentiated thyroid cancer (DTC).
2. Measurable disease meeting the following criterion:

1. At least one lesion (greater than or equal to 1.5 cm in longest diameter for non-lymph nodes and greater than or equal to 2.0 cm in longest diameter for lymph nodes) which is serially and accurately measurable according to modified response evaluation criteria in solid tumours (RECIST) using either computed tomography (CT) or magnetic resonance imaging (MRI).
2. Lesions that have had electron beam radiotherapy must show evidence of progressive disease based on modified RECIST to be deemed a target lesion.
3. Evidence of disease progression by RECIST using site assessment of CT/MRI scans within 12 months (+1 month to allow for variances in patient scanning intervals) prior to study entry.
4. DTC must be 131-I refractory/resistant: never demonstrated 131-I uptake, progression despite 131-I uptake, or cumulative dose of 131-I of greater than 600 millicurie (mCi) (last dose given at least 6 months prior to study entry).
5. Well controlled blood pressure prior to study entry.
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

1. Anaplastic thyroid carcinoma, thyroid lymphoma, mesenchymal tumors of the thyroid, metastases to the thyroid.
2. Brain or leptomeningeal metastases.
3. Significant cardiovascular impairment (history of congestive heart failure, New York Heart Association [NYHA] Class II, unstable angina or myocardial infarction within 6 months of study start, or serious cardiac arrhythmia).
4. Marked baseline prolongation of QT/corrected QT (QTc) interval.
5. Proteinuria greater than 1+ or greater than 30 mg in dipstick testing.
6. Active hemoptysis (bright red blood of at least one-half teaspoon) in the 28 days prior to study entry.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
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
6/11/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/03/2019
Sample size
Target
Accrual to date
Final
117
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
- St Leonards
Recruitment hospital [2] 0 0
- Brisbane
Recruitment hospital [3] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
- St Leonards
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New Hampshire
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
United States of America
State/province [15] 0 0
Wisconsin
Country [16] 0 0
France
State/province [16] 0 0
Lyon
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
France
State/province [18] 0 0
Reims
Country [19] 0 0
France
State/province [19] 0 0
Villejuif Cedex
Country [20] 0 0
Italy
State/province [20] 0 0
Ferrara
Country [21] 0 0
Italy
State/province [21] 0 0
Milan
Country [22] 0 0
Italy
State/province [22] 0 0
Naples
Country [23] 0 0
Italy
State/province [23] 0 0
Pisa
Country [24] 0 0
Italy
State/province [24] 0 0
Rome
Country [25] 0 0
Italy
State/province [25] 0 0
Siena
Country [26] 0 0
Poland
State/province [26] 0 0
Gliwice
Country [27] 0 0
Poland
State/province [27] 0 0
Poznan
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Cardiff
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Glasgow
Country [30] 0 0
United Kingdom
State/province [30] 0 0
London
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Sutton

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine the safety and efficacy of oral lenvatinib in participants with medullary thyroid cancer (MTC) or radioiodine (131 I)-refractory/resistant differentiated thyroid cancer (DTC), unresectable differentiated thyroid cancers, stratified by Histology.
Trial website
https://clinicaltrials.gov/study/NCT00784303
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00784303