Study of Safety and Pharmacokinetics of MK-8242 in Participants With Advanced Solid Tumors (P07650)
26 de julho de 2018 atualizado por: Merck Sharp & Dohme LLC
A Phase I Study to Evaluate the Safety and Tolerability and Pharmacokinetic/Pharmacodynamics of MK-8242 in Patients With Advanced Solid Tumors
This study is being done to evaluate the safety and pharmacokinetic profile of MK-8242 and its active metabolite (M16) in participants with advanced solid tumors.
In Part 1 of the study, the study drug dose will be escalated to determine the maximum tolerated dose (MTD).
In Part 2 of the study, the MTD will be confirmed and the recommended Phase 2 dose (RPTD) established; the effect of MK-8242 on liposarcoma and other tumor types will also be evaluated.
Visão geral do estudo
Descrição detalhada
Participants are considered to have completed the study after Cycle 12. Amendment 4 (14 April 2015) was done to allow participants on active treatment at the time the study was closed to enrollment to continue study treatment beyond Cycle 12 if deriving clinical benefit, at the Investigator's discretion.
Tipo de estudo
Intervencional
Inscrição (Real)
48
Estágio
- Fase 1
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:
- Histologically confirmed advanced solid tumor for which there are no effective standard therapy options
- Willing to provide tumor tissue for p53 wild type gene analysis
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
- Adequate organ function
- Female participants and male participants and their partners who are of childbearing potential must agree to abstain from sexual intercourse or to use an acceptable method of contraception during the study and for 90 days following the last dose of study drug
- At least one measurable lesion
- In Part 2, participants with liposarcoma must have a confirmed well-differentiated or de-differentiated histology
Exclusion criteria:
- Known treated or untreated leptomeningeal metastases, or metastatic central nervous system disease
- History of recent myocardial infarction (within the past year); or with unstable or uncontrolled angina, New York Heart Association (NYHA) Class III or IV congestive heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality
- Uncontrolled active infection on optimal systemic treatment
- Clinically significant hepatitis or hepatitis C antibody positive, hepatitis B surface antigen positive, or human immunodeficiency virus (HIV) seropositive
- Persistent, unresolved common terminology criteria for adverse events (CTCAE v4.0) ≥Grade 2 drug-related toxicity associated with previous treatment except for alopecia
- Radiation therapy or other loco-regional therapy within 2 weeks prior to study
- Use of moderate and strong cytochrome P450 inhibitors or inducers within 1 week prior to study
- Chemotherapy or any investigational drug(s) within 4 weeks prior to study
- Known hypersensitivity to MK-8242 or its components
- Nursing, pregnant, or intention to become pregnant during the study
- Initiating bisphosphonate therapy or adjusting the bisphosphonate dose or regimen within 30 days of Cycle 1 Day 1
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: MK-8242 60 mg BID
In Cycle 1, participants received MK-8242 60 mg administered orally (PO) twice a day (BID) on Days 1-6 and PO once daily (QD) in the morning on Day 7 of the 21-day cycle to accommodate pharmacokinetic (PK) sampling.
In Cycle 2 and subsequent cycles, participants received MK-8242 60 mg PO BID on Days 1-7 of each 21-day cycle.
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10 mg, 100 mg and 150 mg capsules
Outros nomes:
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Experimental: MK-8242 120 mg BID
In Cycle 1, participants received MK-8242 120 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling.
In Cycle 2 and subsequent cycles, participants received MK-8242 120 mg PO BID on Days 1-7 of each 21-day cycle.
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10 mg, 100 mg and 150 mg capsules
Outros nomes:
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Experimental: MK-8242 170 mg BID
In Cycle 1, participants received MK-8242 170 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling.
In Cycle 2 and subsequent cycles, participants received MK-8242 170 mg PO BID on Days 1-7 of each 21-day cycle.
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10 mg, 100 mg and 150 mg capsules
Outros nomes:
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Experimental: MK-8242 250 mg BID
In Cycle 1, participants received MK-8242 250 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling.
In Cycle 2 and subsequent cycles, participants received MK-8242 250 mg PO BID on Days 1-7 of each 21-day cycle.
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10 mg, 100 mg and 150 mg capsules
Outros nomes:
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Experimental: MK-8242 300 mg BID
In Cycle 1, participants received MK-8242 300 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling.
In Cycle 2 and subsequent cycles, participants received MK-8242 300 mg PO BID on Days 1-7 of each 21-day cycle.
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10 mg, 100 mg and 150 mg capsules
Outros nomes:
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Experimental: MK-8242 350 mg BID
In Cycle 1, participants received MK-8242 350 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling.
In Cycle 2 and subsequent cycles, participants received MK-8242 350 mg PO BID on Days 1-7 of each 21-day cycle.
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10 mg, 100 mg and 150 mg capsules
Outros nomes:
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Experimental: MK-8242 400 mg BID
In Cycle 1, participants received MK-8242 400 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling.
In Cycle 2 and subsequent cycles, participants received MK-8242 400 mg PO BID on Days 1-7 of each 21-day cycle.
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10 mg, 100 mg and 150 mg capsules
Outros nomes:
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Experimental: MK-8242 500 mg BID
In Cycle 1, participants received MK-8242 500 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling.
In Cycle 2 and subsequent cycles, participants received MK-8242 500 mg PO BID on Days 1-7 of each 21-day cycle.
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10 mg, 100 mg and 150 mg capsules
Outros nomes:
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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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Number of Participants With Dose Limiting Toxicities (DLTs)
Prazo: Cycle 1 (21 days)
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DLT was defined as: any drug-related hematologic toxicity ≥ Grade 3 lasting ≥1 week, ≥ Grade 3 thrombocytopenia with bleeding, ≥ Grade 3 neutropenia with infection OR non-hematologic DLTs that were any Grade 3, 4, or 5 toxicity with the following exceptions/clarifications: 1) Grade 3 nausea, vomiting, diarrhea, and dehydration were excluded from the determination of DLT if, in the opinion of the investigator and sponsor, they occurred in a setting of inadequate treatment, 2) Grade 3 nausea, vomiting, diarrhea, and dehydration were each considered a DLT if they persisted despite 72 hours of maximal supportive care measures or 3) Any abnormal non-hematological laboratory value ≥ Grade 3 (that is not attributable to any other causes) was considered a DLT only if medical intervention was required to treat the participant, the abnormality led to hospitalization, or the abnormality persisted for ≥1 week.
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Cycle 1 (21 days)
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Maximum Observed Plasma Concentration (Cmax) of MK-8242
Prazo: Cycle 1, Day 1 pre-dose and through 24 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose
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PK plasma samples were to be collected at the following time points: 0, 0.5, 1, 2, 4, 6, 8,and 12 hours after the first dose on Day 1; and 0, 0.5, 1, 2, 4, 6, 8, 12, 24 (Day 8) and 48 (Day 9) hours post-dose on Day 7.
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Cycle 1, Day 1 pre-dose and through 24 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose
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Time to Maximum Plasma Concentration (Tmax) of MK-8242
Prazo: Cycle 1, Day 1 pre-dose and through 12 hours postdose; Cycle 1 Day 7 pre-dose and through 48 hours post dose
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PK plasma samples were to be collected at the following time points: 0, 0.5, 1, 2, 4, 6, 8 and 12 hours after the first dose on Day 1; and 0, 0.5, 1, 2, 4, 6, 8, 12, 24 (Day 8) and 48 (Day 9) hours post-dose on Day 7.
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Cycle 1, Day 1 pre-dose and through 12 hours postdose; Cycle 1 Day 7 pre-dose and through 48 hours post dose
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Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242
Prazo: Cycle 1, Day 1 and Day 7, Hour 0 through Hour 12
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PK plasma samples were to be collected at the following time points: 0, 0.5, 1, 2, 4, 6, 8 and 12 hours after the first dose on Day 1; and 0, 0.5, 1, 2, 4, 6, 8, 12, 24 (Day 8) and 48 (Day 9) hours post-dose on Day 7.
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Cycle 1, Day 1 and Day 7, Hour 0 through Hour 12
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AUC at Time of Last Sample (AUClast) for MK-8242
Prazo: Cycle 1, Day 1 pre-dose and through 12 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose
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PK plasma samples were to be collected at the following time points: 0, 0.5, 1, 2, 4, 6, 8 and 12 hours after the first dose on Day 1; and 0, 0.5, 1, 2, 4, 6, 8, 12, 24 (Day 8) and 48 (Day 9) hours post-dose on Day 7.
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Cycle 1, Day 1 pre-dose and through 12 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Publicações e links úteis
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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)
21 de dezembro de 2011
Conclusão Primária (Real)
15 de setembro de 2014
Conclusão do estudo (Real)
15 de outubro de 2015
Datas de inscrição no estudo
Enviado pela primeira vez
28 de outubro de 2011
Enviado pela primeira vez que atendeu aos critérios de CQ
28 de outubro de 2011
Primeira postagem (Estimativa)
2 de novembro de 2011
Atualizações de registro de estudo
Última Atualização Postada (Real)
27 de agosto de 2018
Última atualização enviada que atendeu aos critérios de controle de qualidade
26 de julho de 2018
Última verificação
1 de julho de 2018
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- P07650
- 2011-001346-15 (Número EudraCT)
- MK-8242-006 (Outro identificador: Merck Protocol Number)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
SIM
Descrição do plano IPD
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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 .