Clinical trial NCT00784303: Evaluating the Safety and Efficacy of Oral Lenvatinib in Medullary and Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers, Stratified by Histology
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Thyroid Cancer
Keywords: Thyroid Cancer
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2008-11-02
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: This study contained 3 Phases: the Pretreatment Phase, the Treatment Phase, and the Extension Phase. The Pretreatment Phase lasted no longer than 28 days. Informed consent was obtained and protocol eligibility and disease characteristics were established prior to treatment. The Treatment Phase consisted of a Treatment Period and a Follow-up Period. The Treatment Period of the Treatment Phase began at the time that the first participant began study drug administration and ended at the time when all participants enrolled completed 8 cycles of treatment or discontinued study treatment prior to the eighth cycle (ie, time of data cutoff for the primary study analysis \[Primary Completion Date\]). All participants then entered the Extension Phase. The Extension Phase consisted of a Treatment Period and a Follow-up Period. The Extension Phase began immediately after the Treatment Phase ended and included all participants that were either still receiving treatment or in follow-up. The time of data cutoff for the primary study analysis occurred when all subjects in the study completed 8 cycles of treatment or discontinued study treatment prior to the eighth cycle.

Eligibility 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.

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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 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
measure: Plasma Pharmacokinetics (PK): Steady State Area Under the Plasma Concentration Curve (AUC)
timeFrame: 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 outcomes:
measure: Change From Baseline in Free Thyroxine (T4)
timeFrame: 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)
measure: Change From Baseline in Free Thyroid Stimulating Hormone (TSH)
timeFrame: 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)
measure: Percent Change From Baseline in Concentrations of Thyroglobulin (DTC Only)
timeFrame: 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)
measure: Percent Change From Baseline in Concentrations of Calcitonin (MTC Only)
timeFrame: 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)
measure: Percent Change From Baseline in Concentrations of Carcinoembryonic Antigen (CEA) (MTC Only)
timeFrame: 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)
measure: Change From Baseline in Concentrations of Cytochrome C (CytoC)
timeFrame: 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)
measure: Change From Baseline in Concentrations of M-30 Neo-Antigen
timeFrame: 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)
measure: Change From Baseline in Concentrations of Activated Caspase 3/7 (Casp 3/7)
timeFrame: 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)
measure: Duration of Response (DoR) Assessed as Per Independent Imaging Reviewers (IIR)
timeFrame: 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
measure: Disease Control Rate (DCR) Assessed as Per IIR
timeFrame: 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
measure: Clinical Benefit Rate (CBR) Assessed as Per IIR
timeFrame: 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
measure: Time to Response (TTR) Assessed as Per IIR
timeFrame: From date of treatment start until date of first CR or PR, assessed up to data cutoff date 11 April 2011
measure: Progression Free Survival (PFS) Assessed as Per IIR
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: 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
measure: Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib
timeFrame: For each participant, from the first dose till 30 days after the last dose of study treatment (up to approximately 10 years 4 months)
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Los Angeles
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state: California
city: Los Gatos
country: United States
state: California
city: Mission Viejo
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state: California
city: Santa Monica
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state: California
city: Torrance
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state: California
city: Aurora
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state: Colorado
city: Orlando
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state: Florida
city: Tampa
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state: Florida
city: Roswell
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state: Georgia
city: Chicago
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state: Illinois
city: Baltimore
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state: Maryland
city: Bethesda
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Minneapolis
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state: Minnesota
city: Columbia
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state: Missouri
city: Jefferson City
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state: Missouri
city: Lebanon
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state: New Hampshire
city: Montclair
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state: New Jersey
city: Houston
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state: Texas
city: Long Beach
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state: Washington
city: Seattle
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state: Washington
city: Madison
country: United States
state: Wisconsin
city: St Leonards
country: Australia
state: New South Wales
city: Brisbane
country: Australia
city: Melbourne
country: Australia
city: Lyon
country: France
city: Paris
country: France
city: Reims
country: France
city: Villejuif Cedex
country: France
city: Ferrara
country: Italy
city: Milan
country: Italy
city: Naples
country: Italy
city: Pisa
country: Italy
city: Rome
country: Italy
city: Siena
country: Italy
city: Gliwice
country: Poland
city: Poznan
country: Poland
city: Cardiff
country: United Kingdom
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
References: