Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer (SELECT-3)
12 de março de 2018 atualizado por: AstraZeneca
A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination With First Line Chemotherapy Regimens in Patients With Non-Small Cell Lung Cancer (NSCLC)
This is a Phase I, open label multicentre study of selumetinib administered orally in combination with first line chemotherapy regimens to patients with advanced/metastatic NSCLC. The study has been designed to allow an investigation of the optimal dose of selumetinib in combination with various standard first line double-platinum chemotherapy regimens. Initial assessment will be based on tolerability of selumetinib in combination with one or more selected regimens that are considered to be tolerated also being assessed for preliminary evidence of activity.
This study is a dose finding and optional cohort expansion; In addition all patients will be assessed for anti-cancer efficacy of the combination of selumetinib and chemotherapy.
Visão geral do estudo
Status
Concluído
Descrição detalhada
A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination with First Line Chemotherapy Regimens in Patients with Non-Small Cell Lung Cancer (NSCLC)
Tipo de estudo
Intervencional
Inscrição (Real)
55
Estágio
- Fase 1
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
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Glasgow, Reino Unido, G12 0YN
- Research Site
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London, Reino Unido, W1G 6AD
- Research Site
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Manchester, Reino Unido, M20 4BX
- Research Site
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Newcastle upon Tyne, Reino Unido, NE7 7DN
- Research Site
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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:
- Provision of signed, written and dated consent prior to any study specific procedures
- Male or female, aged 18 years or older
- Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)
- Female patients must not be breast-feeding and have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential
- Patients must be eligible to receive treatment with the platinum doublet combination with which selumetinib is being combined and in accordance with the local product information
Exclusion Criteria:
- Prior chemotherapy or other systemic anti-cancer treatment for advanced NSCLC.
- Prior surgery or radiotherapy within 6 months or palliative radiotherapy within 4 weeks of start of study treatment.
- Female patients who are breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
- Another primary malignancy within 5 years of starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
- As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, active bleeding diatheses, renal transplant, or active infection
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: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Selumetinib+standard chemotherapy
Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin
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2 x 25mg capsules bd continuously in cohort 1 (with gemcitabine and cisplatin).
If tolerated - next cohort 3 x 25mg capsules bd continuously.
if higher doses are explored, required number of capsules will be provided.
Option to administer on D2-19 of each 21 day cycle if required to assess tolerability of combinations with chemotherapy
1250 mg/m2 iv on Day 1 and 8 of each 21 day cycle.
If combination not tolerated, option to give 1000 mg/m2 iv on Day 1 and Day 8 of each 21 day cycle
75 mg/m2 iv on Day 1 of each 21 day cycle.
If combination not tolerated, option to give 50 mg/m2 iv on Day 1 or 25mg/m2 iv on Day 1 and Day 8 of each 21 day cycle
If it is not possible to identify a tolerable combination of selumetinib, gemcitabine and cisplatin, cisplatin may be replaced with carboplatin (AUC5) iv on Day 1 of each 21 day cycle
Gemcitabine may be replaced with pemetrexed 500 mg/m2 iv on Day 1 of each 21 day cycle.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib
Prazo: The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks
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Any toxicity not attributable to the disease or disease-related processess under investigation, considered related to the combination of chemotherapy plus selumetinib, which occurs within the timeframe and is dose limiting
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The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Best Objective Response
Prazo: Screening, week 6 and week 12
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The best response a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression.
Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions, the sum must also demonstrate an absolute increase of >=5mm; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm
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Screening, week 6 and week 12
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Percentage Change From Baseline at 6 Weeks in Target Lesion Size
Prazo: Week 6
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The percentage change in the sum of the diameters of target lesions
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Week 6
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Best Percentage Change From Baseline in Target Lesion Size
Prazo: Screening, week 6 and week 12
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The best percentage change in tumour size a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression.
Percentage change was derived at each visit by the percentage change in the sum of the diameters of target lesions
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Screening, week 6 and week 12
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Objective Response Rate (ORR)
Prazo: Up until progression or last evaluable assessment in the absence of progression, up to 9 months
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The number of patients who had at least 1 confirmed visit response of Complete Response (CR) or Partial Response (PR) prior to any evidence of progression.
Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm; Objective Response Rate (ORR) = CR + PR
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Up until progression or last evaluable assessment in the absence of progression, up to 9 months
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AUC (0-tau)
Prazo: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Area under the concentration time curve (AUC) over a dosing interval at steady state (0-tau)
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Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Cmax,ss
Prazo: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Maximum plasma concentration at steady state
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Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Tmax,ss
Prazo: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Time to reach maximum plasma concentration at steady state
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Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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CL/F
Prazo: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Apparent oral plasma clearance
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Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Diretor de estudo: Gabriella Mariani, MD, AstraZeneca UK, MSD
- Investigador principal: Emma Dean, BMEDSCI, BM, BS, PHD, The Christie NHS Foundation Trust, UK
- Investigador principal: Fiona Blackhall, PhD, FRCP, The Christie NHS Foundation Trust Clinical Trials Unit; UK
Publicações e links úteis
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Links úteis
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)
4 de abril de 2013
Conclusão Primária (Real)
4 de janeiro de 2016
Conclusão do estudo (Real)
4 de janeiro de 2016
Datas de inscrição no estudo
Enviado pela primeira vez
8 de março de 2013
Enviado pela primeira vez que atendeu aos critérios de CQ
11 de março de 2013
Primeira postagem (Estimativa)
12 de março de 2013
Atualizações de registro de estudo
Última Atualização Postada (Real)
13 de março de 2018
Última atualização enviada que atendeu aos critérios de controle de qualidade
12 de março de 2018
Última verificação
1 de março de 2018
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças Respiratórias
- Neoplasias
- Doenças pulmonares
- Neoplasias por local
- Neoplasias do Trato Respiratório
- Neoplasias Torácicas
- Carcinoma Broncogênico
- Neoplasias Brônquicas
- Neoplasias Pulmonares
- Carcinoma pulmonar de células não pequenas
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Agentes Anti-Infecciosos
- Antivirais
- Inibidores da Síntese de Ácido Nucleico
- Inibidores Enzimáticos
- Antimetabólitos, Antineoplásicos
- Antimetabólitos
- Agentes Antineoplásicos
- Agentes imunossupressores
- Fatores imunológicos
- Antagonistas do ácido fólico
- Gemcitabina
- Carboplatina
- Cisplatina
- Pemetrexede
Outros números de identificação do estudo
- D1532C00070
- EudraCT number: 2012-005202-22
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