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Evaluating the Safety and Efficacy of Oral Lenvatinib in Medullary and Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers, Stratified by Histology

3 de abril de 2020 atualizado por: Eisai Inc.

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

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.

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Descrição detalhada

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.

Tipo de estudo

Intervencional

Inscrição (Real)

117

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • Austrália
      • Brisbane, Austrália
      • Melbourne, Austrália
    • New South Wales
      • St Leonards, New South Wales, Austrália
  • Estados Unidos
    • Arkansas
      • Little Rock, Arkansas, Estados Unidos
    • California
      • Los Angeles, California, Estados Unidos
      • Los Gatos, California, Estados Unidos
      • Mission Viejo, California, Estados Unidos
      • Santa Monica, California, Estados Unidos
      • Torrance, California, Estados Unidos
    • Colorado
      • Aurora, Colorado, Estados Unidos
    • Florida
      • Orlando, Florida, Estados Unidos
      • Tampa, Florida, Estados Unidos
    • Georgia
      • Roswell, Georgia, Estados Unidos
    • Illinois
      • Chicago, Illinois, Estados Unidos
    • Maryland
      • Baltimore, Maryland, Estados Unidos
      • Bethesda, Maryland, Estados Unidos
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos
    • Minnesota
      • Minneapolis, Minnesota, Estados Unidos
    • Missouri
      • Columbia, Missouri, Estados Unidos
      • Jefferson City, Missouri, Estados Unidos
    • New Hampshire
      • Lebanon, New Hampshire, Estados Unidos
    • New Jersey
      • Montclair, New Jersey, Estados Unidos
    • Texas
      • Houston, Texas, Estados Unidos
    • Washington
      • Long Beach, Washington, Estados Unidos
      • Seattle, Washington, Estados Unidos
    • Wisconsin
      • Madison, Wisconsin, Estados Unidos
  • França
      • Lyon, França
      • Paris, França
      • Reims, França
      • Villejuif Cedex, França
  • Itália
      • Ferrara, Itália
      • Milan, Itália
      • Naples, Itália
      • Pisa, Itália
      • Rome, Itália
      • Siena, Itália
  • Polônia
      • Gliwice, Polônia
      • Poznan, Polônia
  • Reino Unido
      • Cardiff, Reino Unido
      • Glasgow, Reino Unido
      • London, Reino Unido
      • Sutton, Reino Unido

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 99 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Não randomizado
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: DTC cohort
This arm will enroll participants with radioiodine (131 I)-refractory/resistant differentiated thyroid cancer.
Medicamento: 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.
Outros nomes:
  • E7080, LENVIMA
Experimental: MTC cohort
This arm will enroll participants with medullary thyroid cancer.
Medicamento: 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.
Outros nomes:
  • E7080, LENVIMA

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Objective Response Rate (ORR)
Prazo: 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
ORR was the percentage of participants with best overall response (BOR) of complete response (CR) and partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 for target lesions using magnetic resonance imaging/computed tomography (MRI/CT) scans, as determined by independent imaging review (IIR). CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. ORR=CR+PR, was presented with 2-sided 95% confidence interval (CI) by the method of Clopper and Pearson.
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
Plasma Pharmacokinetics (PK): Steady State Area Under the Plasma Concentration Curve (AUC)
Prazo: 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)
Up to 9 samples per participant were obtained at specific time points. Plasma concentrations of lenvatinib were analyzed using standard analysis methods. Due to the sparse PK sampling in this study, the data were pooled with data from other Phase 1 studies conducted in participants with solid tumors for PK model development and covariate analysis. Individual exposure (steady state AUC) to lenvatinib in MTC and DTC subjects in this study was derived based on the individual predicted steady state AUC from the final PK model. Only data for participants taking 24 mg lenvatinib daily were reported (participants taking 20 mg lenvatinib daily were not included in this data set).
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)

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Change From Baseline in Free Thyroxine (T4)
Prazo: 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)
Blood samples to measure free T4 were collected at Screening (Baseline), Cycle 1 Day 15 (MTC cohort), Day 1 of Cycles 2 to 20, and Final Visit. Changes in free T4 concentration values from baseline to specific time points were calculated. Only participants with both baseline and relevant visit values were included.
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)
Change From Baseline in Free Thyroid Stimulating Hormone (TSH)
Prazo: 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)
Blood samples to measure free TSH were collected at Screening (Baseline), Cycle 1 Day 15 (MTC cohort), Day 1 of Cycles 2 to 20, and Final Visit. Changes in free TSH concentration values from baseline to specific time points were calculated. Only participants with both baseline and relevant visit values were included. For any free TSH result that was reported as <0.008 mIU/L, 0.004 mIU/L was used for calculating summary statistics.
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)
Percent Change From Baseline in Concentrations of Thyroglobulin (DTC Only)
Prazo: 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)
Blood samples to obtain serum were collected at Cycle 1 Day 1 (Baseline), Day 1 of Cycles 2 to 19, Final Visit, and were analyzed for thyroglobulin concentration. Percent changes in thyroglobulin concentration values from baseline to specific time points were calculated. Only participants with both baseline and relevant visit values were included.
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)
Percent Change From Baseline in Concentrations of Calcitonin (MTC Only)
Prazo: 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)
Blood samples to obtain serum were collected at Cycle 1 Day 1(Baseline), Day 1 of Cycles 2 to 20, Final Visit, and were analyzed for calcitonin concentration. Percent changes in calcitonin concentration values from baseline to specific time points were calculated. Only participants with both baseline and relevant visit values were included.
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)
Percent Change From Baseline in Concentrations of Carcinoembryonic Antigen (CEA) (MTC Only)
Prazo: 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)
Blood samples were collected at Cycle 1 Day 1(Baseline), Day 1 of Cycles 2 to 20, Final Visit, and were analyzed for CEA concentration. Percent changes in CEA concentration values from baseline to specific time points were calculated. Only participants with both baseline and relevant visit values were included.
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)
Change From Baseline in Concentrations of Cytochrome C (CytoC)
Prazo: 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)
Blood samples to obtain serum were collected at Cycle 1 Day 1(Baseline), Cycle 1 Day 8, Cycle 2 Days 1,8 &15, Cycles 3 to 9,11,13 Day 1, Final Visit, and analyzed for CytoC concentration. Changes in CytoC concentration values from baseline to specific time points were calculated. Only participants with both baseline and relevant visit values were included. For results reported as below quantifiable level (BQL), zero was used for calculating summary statistics. If more than 50% of the results at a visit were BQL, then only 'n', 'minimum' and 'maximum' were calculated for summary statistics.
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)
Change From Baseline in Concentrations of M-30 Neo-Antigen
Prazo: 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)
Blood samples to obtain serum were collected at Cycle 1 Day 1(Baseline), Cycle 1 Day 8, Cycle 2 Days 1,8 &15, Cycles 3 to 9,11,13 Day 1, Final Visit, and analyzed for M-30 concentration. Changes in M-30 concentration values from baseline to specific time points were calculated. Only participants with both baseline and relevant visit values were included. For results reported as BQL, zero was used for calculating summary statistics. If more than 50% of the results at a visit were BQL, then only 'n', 'minimum' and 'maximum' were calculated for summary statistics.
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)
Change From Baseline in Concentrations of Activated Caspase 3/7 (Casp 3/7)
Prazo: 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)
Blood samples to obtain serum were collected at Cycle 1 Day 1 (Baseline), Cycle 1 Day 8, Cycle 2 Days 1, 8, and 15, Cycles 3 to 9, 11, 13 (Day 1), Final Visit, and analyzed for Casp 3/7 concentration. Changes in Casp 3/7 concentration values from baseline to specific time points were calculated. Only participants with both baseline and relevant visit values were included. The concentrations of Casp 3/7 were BQL for most participants at most time points. For results reported as BQL, zero was used for calculating summary statistics. If more than 50% of the results at a visit were BQL, then only 'n', 'minimum' and 'maximum' were calculated for summary statistics.
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)
Duration of Response (DoR) Assessed as Per Independent Imaging Reviewers (IIR)
Prazo: 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
DoR was based on IIR was the time from date of the first CR or PR until the date of first documentation of disease progression or date of death, if death occurred prior to disease progression, for the participants who had BOR of CR or PR. Participants without progressive disease or death were censored at the date of last adequate tumor assessment. Duration of response = End Date - Date of first CR or PR + 1
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
Disease Control Rate (DCR) Assessed as Per IIR
Prazo: 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
DCR was the percentage of the participants who had BOR of CR, PR, and stable disease (SD) with the minimum duration of SD lasting greater than or equal to 7 weeks, based on assessments by IIR. DCR = CR+PR+SD greater than or equal to 7 weeks
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
Clinical Benefit Rate (CBR) Assessed as Per IIR
Prazo: 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
CBR was the percentage of the participants who had BOR of CR, PR, and SD with the minimum duration of SD lasting greater than or equal to 23 weeks, based on assessments by IIR. CBR = CR+PR+SD greater than or equal to 23 weeks
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
Time to Response (TTR) Assessed as Per IIR
Prazo: From date of treatment start until date of first CR or PR, assessed up to data cutoff date 11 April 2011
TTR was defined as "time from start of treatment to the time when a participant first achieves a response of PR/CR" based on assessments by IIR. TTR was only calculated for participants with confirmed PR or CR.
From date of treatment start until date of first CR or PR, assessed up to data cutoff date 11 April 2011
Progression Free Survival (PFS) Assessed as Per IIR
Prazo: 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
PFS was defined as the time from the date of treatment start until progressive disease or death from any cause in the absence of progressive disease. Disease progression was defined as at least a 20% increase in the sum of the longest diameter 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 as assessed by IIR using RECIST 1.0. The duration of PFS was calculated as end date minus date of first drug plus 1, based on assessments by IIR. PFS was calculated using Kaplan-Meier estimate and presented with 2-sided 95% Cl.
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
Overall Survival (OS)
Prazo: 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
OS was defined as the time from the date of treatment start until death from any cause. The duration of OS was calculated as 'end date minus date of first drug plus 1', based on assessments by IIR. Participants without a reported death or those lost to follow-up were censored at their last known alive date at the database cutoff. OS was calculated using Kaplan-Meier estimate and presented with 2-sided 95% Cl.
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
Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib
Prazo: For each participant, from the first dose till 30 days after the last dose of study treatment (up to approximately 10 years 4 months)
Safety assessments consisted of monitoring and recording all AEs (serious and non-serious) and SAEs; concomitant medications, regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, New York Heart Association (NYHA) assessments, electrocardiograms (ECGs), echocardiograms; and performance of physical examinations.
For each participant, from the first dose till 30 days after the last dose of study treatment (up to approximately 10 years 4 months)

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Eisai Inc.

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

6 de novembro de 2008

Conclusão Primária (Real)

11 de abril de 2011

Conclusão do estudo (Real)

29 de março de 2019

Datas de inscrição no estudo

Enviado pela primeira vez

30 de outubro de 2008

Enviado pela primeira vez que atendeu aos critérios de CQ

31 de outubro de 2008

Primeira postagem (Estimativa)

2 de novembro de 2008

Atualizações de registro de estudo

Última Atualização Postada (Real)

22 de abril de 2020

Última atualização enviada que atendeu aos critérios de controle de qualidade

3 de abril de 2020

Última verificação

1 de março de 2019

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • E7080-G000-201

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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