A Study of LY2875358 in Participants With Advanced Cancer
14 de fevereiro de 2017 atualizado por: Eli Lilly and Company
A Phase 1 Study of LY2875358 in Patients With Advanced Cancer
The objective of this study is to determine a recommended Phase 2 dose range of LY2875358 that may be safely administered to participants with advanced cancer.
In Part A and Part A2 of this study, escalating doses of LY2875358 as monotherapy and in combination with erlotinib will be evaluated for safety and tolerability, respectively.
Part B is a dose-confirmation segment for LY2875358 therapy in 5 different types of cancer: nonsquamous non-small cell lung cancer (NSCLC), castrate resistant prostate cancer (CRPC) with bone metastases, renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), or uveal melanoma with liver metastases, and for LY2875358 in combination with trametinib in participants with uveal melanoma with liver metastases.
Visão geral do estudo
Status
Concluído
Condições
Descrição detalhada
Protocol amendment (November, 2013) expanded Part B to study LY2875358 in combination with trametinib in participants with uveal melanoma with liver metastasis.
Tipo de estudo
Intervencional
Inscrição (Antecipado)
117
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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California
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La Jolla, California, Estados Unidos, 92037-0845
- University of California - San Diego
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Los Angeles, California, Estados Unidos, 90048-5615
- Cedars Sinai Medical Center
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San Francisco, California, Estados Unidos, 94115
- Univ of California San Francisco
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Santa Monica, California, Estados Unidos, 90404
- UCLA
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Florida
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Jacksonville, Florida, Estados Unidos, 32224
- Mayo Clinic of Jacksonville
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Emory University
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109-0946
- University of Michigan
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Minnesota
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Rochester, Minnesota, Estados Unidos, 55902
- Mayo Clinic
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19107
- Thomas Jefferson University
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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 e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Part A: Have histological or cytological evidence of cancer (solid tumor, lymphoma, or multiple myeloma) that is advanced and/or metastatic and an appropriate candidate for experimental therapy
- Part A2: Histologic or cytologic diagnosis of advanced Non Small Cell Lung Cancer (NSCLC), Stage IIIB with malignant pleural effusion or Stage IV, completed at least 1 prior systemic regimen, and eligible for erlotinib therapy.
- Part B: Candidate for experimental therapy after standard therapies used or non-eligible for standard therapies. Histological or cytological evidence of 1 of the 5 tumor types:
Castrate-resistant prostate cancer (CRPC) with bone metastasis:
--Progressive Disease in the setting of castrate level of testosterone
Renal Cell Carcinoma (RCC):
--Histologic diagnosis of either clear-cell or papillary RCC (metastatic and unresectable, or bilateral, multifocal, unresectable RCC localized to kidneys).
NSCLC:
--Histologic or cytologic diagnosis of advanced NSCLC, Stage IIIB with malignant pleural effusion or Stage IV
Hepatocellular Carcinoma (HCC)
--Histologic or cytologic diagnosis of hepatocellular carcinoma
- Uveal Melanoma with liver metastasis
- Part A: Have the presence of measurable or nonmeasurable disease as defined by the RECIST v1.1 (Eisenhauer et al. 2009) or Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) or have measureable disease for multiple myeloma.
- Part A2 & B (RCC, NSCLC, HCC, and uveal melanoma): Have measurable disease as defined by RECIST v1.1.
- Give written informed consent prior to any study-specific procedures.
- Adequate organ function.
- Performance status of less than or equal to 2 on ECOG scale.
- Discontinued all previous cancer therapies, and any agents that have not received regulatory approval, for at least 21 days and recovered from the acute effects of therapy. Must have discontinued mitomycin-C or nitrosourea therapy for at least 42 days.
- Reliable and available for the duration of the study and willing to follow study procedures.
- Males and females (reproductive potential): Use medically approved contraceptive precautions during the study and for 4 months following the last dose of study drug.
- Females (childbearing potential): Have had a negative serum pregnancy test before the first dose of study drug and not be breast-feeding.
- Estimated life expectancy that will permit the participants to complete 8 weeks of treatment.
Exclusion Criteria:
- Serious preexisting medical conditions
- Symptomatic central nervous system malignancy or metastasis (screening not required).
- Acute or chronic leukemia.
- Active infection including HIV, hepatitis A, B or C
- Have second primary malignancy that may affect the interpretation of results.
- Have received a liver transplant, or have liver cirrhosis with a Child-Pugh Stage of B or C.
- Patients with active alcohol abuse, as determined by the treating investigator.
- Part A2: Unable to swallow tablets. Intolerant of therapy with erlotinib. Concomitant treatment with the cytochrome P450 3A (CYP3A) modulators. Must not have received treatment with any of these modulators within 14 days of study treatment.
- Have a history of New York Heart Association class ≥3, unstable angina, myocardial infarction 6 months prior to study drug
- QTc greater than 470 msec.
- Received previous treatment with any c-MET experimental therapeutic.
Part B Expansion Cohort 1 (CRPC):
- Increasing use of daily doses of opioid analgesics within 28 days prior to enrollment in the study.
- Neuroendocrine prostate cancer.
- Patients who have a solitary bone metastasis that has been irradiated are not eligible.
- Part B Expansion Cohort 6 (LY2875358 plus trametinib in participants with uveal melanoma with liver metastasis): Contra-indications for trametinib
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 |
|---|---|
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Experimental: LY2875358
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Part A Dose escalation of LY2875358 administered intravenously (IV), Day 1 and 15 every 28 days for at least two cycles.
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Experimental: LY2875358 + erlotinib
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Part A2 Dose escalation of LY2875358 administered IV, on Day 1 and 15 every 28 days for at least two cycles in combination with daily erlotinib dosing (150 mg) taken orally (PO).
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Experimental: LY2875358 at Part A highest dose
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Part B (Dose Exploration): LY2875358 at Part A highest dose administered IV, on Day 1 and 15 every 28 days for at least two cycles.
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Experimental: LY2875358 at Part A highest dose + trametinib
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Part B (in combination with trametinib): LY2875358 at Part A highest dose administered IV, on Day 1 and 15 every 28 days for at least two cycles, in combination with trametinib at 2 mg orally once daily
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
|---|---|
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Recommended Phase 2 dose range of LY2875358 monotherapy and in combination with erlotinib
Prazo: Baseline through Cycle 1
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Baseline through Cycle 1
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Medidas de resultados secundários
Medida de resultado |
Prazo |
|---|---|
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Pharmacokinetics: Maximum plasma concentration (Cmax)
Prazo: Days 1, 2, 4, 5, 6, 8, 15, and 22 of Cycle 1. Days 1, 15, and 22 of Cycle 2. Days 1 and 15 of Cycles 3 and beyond, as well as 14 days, 29 days, and 57 days following the final treatment
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Days 1, 2, 4, 5, 6, 8, 15, and 22 of Cycle 1. Days 1, 15, and 22 of Cycle 2. Days 1 and 15 of Cycles 3 and beyond, as well as 14 days, 29 days, and 57 days following the final treatment
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Number of participants with a tumor response
Prazo: Baseline to study completion (12 months)
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Baseline to study completion (12 months)
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Pharmacokinetics: Area under the concentration-time curve (AUC)
Prazo: Days 1, 2, 4, 5, 6, 8, 15, and 22 of Cycle 1. Days 1, 15, and 22 of Cycle 2. Days 1 and 15 of Cycles 3 and beyond, as well as 14 days, 29 days, and 57 days following the final treatment
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Days 1, 2, 4, 5, 6, 8, 15, and 22 of Cycle 1. Days 1, 15, and 22 of Cycle 2. Days 1 and 15 of Cycles 3 and beyond, as well as 14 days, 29 days, and 57 days following the final treatment
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Time to progression and overall survival
Prazo: Baseline to study completion (12 months)
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Baseline to study completion (12 months)
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Pharmacokinetics: Area under the concentration-time curve (AUC) of erlotinib or trametinib in combination with LY2875358
Prazo: Cycle 1
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Cycle 1
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Change from baseline in Brief Pain Inventory (BPI) in Part B: Expansion Cohort 1
Prazo: Baseline to study completion (12 months)
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Baseline to study completion (12 months)
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
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)
13 de abril de 2010
Conclusão Primária (Real)
8 de janeiro de 2015
Conclusão do estudo (Real)
26 de outubro de 2016
Datas de inscrição no estudo
Enviado pela primeira vez
28 de janeiro de 2011
Enviado pela primeira vez que atendeu aos critérios de CQ
31 de janeiro de 2011
Primeira postagem (Estimativa)
1 de fevereiro de 2011
Atualizações de registro de estudo
Última Atualização Postada (Real)
15 de fevereiro de 2017
Última atualização enviada que atendeu aos critérios de controle de qualidade
14 de fevereiro de 2017
Última verificação
1 de fevereiro de 2017
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 13298
- I4C-MC-JTBA (Outro identificador: Eli Lilly and Company)
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