BI 860585 Dose Escalation Single Agent and in Combination With Exemestane or With Paclitaxel in Patients With Various Advanced and/or Metastatic Solid Tumors
19 de junho de 2018 atualizado por: Boehringer Ingelheim
An Open Label Phase I Dose Finding Study of BI 860585 Administered Orally in a Continuous Dosing Schedule as Single Agent and in Combination With Exemestane or With Paclitaxel in Patients With Various Advanced and/or Metastatic Solid Tumours
The primary objective of the trial is to determine the maximum tolerated doses (MTD) of BI 860585 alone and in combination with exemestane or paclitaxel.
To determine the MTDs, patients are entered sequentially into escalating dose cohorts.
Secondary objectives are objective response and disease control according to RECIST criteria version 1.1
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Tipo de estudo
Intervencional
Inscrição (Real)
90
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.
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:
- Patients with histologically or cytologically confirmed diagnosis of advanced, measurable or evaluable, non-resectable and/or metastatic solid tumours, which has shown to be progressive;
- Patients who have received previous standard of care therapy for their disease and have progressed;
- 18 years or older;
- Life expectancy >= 3 months;
- Written informed consent in accordance with International Conference on Harmonisation/Good Clinical Practice (ICH/GCP) and local legislation;
- Eastern Cooperative Oncology Group (ECOG), performance score 0-2.
Additional inclusion criteria for the combination arms:
- Patients must have confirmed progressive disease within the last 6 months, (in case of measurable disease, progression should be confirmed according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1;
- Patients carrying a tumour for whom treatment with either exemestane or paclitaxel would be considered appropriate by the investigator;
Additional inclusion criteria for expansion part:
- Patients must have measurable progressive disease within the last 6 months documented/proven according to RECIST criteria version 1.1.
- Patients entering the expansion cohorts must also have:
- Arm A: any advanced/metastatic solid tumour suitable for biopsy and must have provided informed consent for biopsy and biomarker analysis.
- Arm B: any cytologically or histologically confirmed ER+ (estrogen receptor positive) advanced/metastatic solid tumours for which treatment with exemestane would be considered appropriate by the investigator.
- Arm C: any advanced/metastatic solid tumour for which treatment with paclitaxel would be considered appropriate by the investigator.
Exclusion criteria:
- Serious concomitant non-oncological disease/illness considered by the investigator to be incompatible with the protocol;
- Patients with untreated or symptomatic brain metastases;
- Second malignancies requiring active therapy;
- Clinical Congestive Heart Failure (CHF) Grade III-IV;
- Myocardial infarction within the last 6 months prior to inclusion, or symptomatic coronary artery disease;
- Adequate bone marrow, liver and renal function;
- Patients with known HIV/hepatitis/active infectious disease considered by the investigator to be incompatible with the protocol;
- Patients unable to take oral medication;
- Chronic diarrhoea or other gastrointestinal disorders;
- Treatment with anti-cancer-therapies: cytotoxic or standard chemotherapy, immunotherapy, radiotherapy, biological therapies, molecular targeted or other investigational drugs, within four weeks of the first treatment with the study medication (or within one week for non-cytotoxic drugs);
- Recovery from previous surgery and anticancer medical treatments;
- Hypersensitivity to combination drugs or excipients;
- Patients with a history of uncontrolled diabetes mellitus.
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 Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: BI 860585
Multiple ascending doses of BI 860585 administered continuously in a 28-day cycle, including food interaction cohorts
|
BI 860585 multiple dose escalation, once daily
|
|
Experimental: BI 860585 + paclitaxel
Multiple ascending doses of BI 860585 in combination with fixed dose paclitaxel
|
BI 860585 multiple dose escalation, once daily
paclitaxel once weekly
|
|
Experimental: BI 860585 + exemestane
Multiple ascending doses of BI 860585 in combination with fixed dose exemestane
|
BI 860585 multiple dose escalation, once daily
exemestane once daily
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
The Number of Patients With Dose-Limiting Toxicities (DLTs) in the First Course of Each Treatment Arm
Prazo: 28 days (Maximum tolerated dose (MTD) evaluation period (First Treatment Cycle))
|
The number of patients with Dose-Limiting Toxicities (DLTs) in the first course of each treatment arm to identify the Maximum Tolerated Dose (MTD) for BI 860585 monotherapy and BI 860585 in combination with exemestane of paclitaxel.
|
28 days (Maximum tolerated dose (MTD) evaluation period (First Treatment Cycle))
|
|
The Maximum Tolerated Dose (MTD) for Each Treatment Arm
Prazo: 28 days (Maximum tolerated dose (MTD) evaluation period (First Treatment Cycle))
|
The Maximum Tolerated Dose (MTD) for each treatment arm was the dose that was 1 dose cohort below that at which ≥2 of 6 patients had experienced DLT.
i.e., the MTD was the highest dose studied for which the DLT incidence was no more than 17% (i.e. 1 of 6 patients) during the first treatment course.
|
28 days (Maximum tolerated dose (MTD) evaluation period (First Treatment Cycle))
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Objective Response Rate (Complete Response or Partial Response as Per the Response Evaluation Criteria In Solid Tumors Criteria [RECIST], Version 1.1)
Prazo: From the date of first treatment administration until the earliest of disease progression, death, or last adequate tumour assessment before new anti-cancer therapy; data collected up to cut-off date 30 Jun 2017, Up to 1389 days
|
As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for objective response rate (Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions) for target lesions assessed by Magnetic resonance imaging (MRI) and Computed tomography (CT)
|
From the date of first treatment administration until the earliest of disease progression, death, or last adequate tumour assessment before new anti-cancer therapy; data collected up to cut-off date 30 Jun 2017, Up to 1389 days
|
|
Disease Control Rate/Clinical Benefit Rate (Complete Response, Partial Response or Stable Disease as Per Response Evaluation Criteria In Solid Tumors Criteria [RECIST], Version 1.1)
Prazo: From the date of first treatment administration until the earliest of disease progression, death, or last adequate tumour assessment before new anti-cancer therapy.
|
As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for disease control rate/clinical benefit rate (Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression) for target lesions assessed by Magnetic resonance imaging (MRI) and Computed tomography (CT)
|
From the date of first treatment administration until the earliest of disease progression, death, or last adequate tumour assessment before new anti-cancer therapy.
|
|
Duration of Clinical Benefit
Prazo: From the date of first treatment administration until the earliest of disease progression, death, or last adequate tumour assessment before new anti-cancer therapy; data collected up to cut-off date 30 Jun 2017, Up to 1389 days
|
Duration of clinical benefit (Disease control) was defined as the time between first treatment administration until the earliest of disease progression or death, for patients with disease control.
|
From the date of first treatment administration until the earliest of disease progression, death, or last adequate tumour assessment before new anti-cancer therapy; data collected up to cut-off date 30 Jun 2017, Up to 1389 days
|
|
Duration of Objective Response
Prazo: From the date of first treatment administration until the earliest of disease progression, death, or last adequate tumour assessment before new anti-cancer therapy; data collected up to cut-off date 30 Jun 2017, Up to 1389 days
|
Duration of objective response was defined as the time from first objective response until the earliest of progression or death, for patients with objective response.
|
From the date of first treatment administration until the earliest of disease progression, death, or last adequate tumour assessment before new anti-cancer therapy; data collected up to cut-off date 30 Jun 2017, Up to 1389 days
|
|
Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to Infinity (AUC0-∞)
Prazo: Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585.
|
AUC0-∞, area under the concentration-time curve in plasma of BI 860585 over the time interval from 0 to infinity after single administration of BI 860585
|
Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585.
|
|
Area Under the Concentration-time Curve in Plasma of BI 860585 Over the Time Interval From 0 to 24 Hours (AUC0-24)
Prazo: Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585.
|
AUC0-24, area under the concentration-time curve in plasma of BI 860585 over the time interval from 0 to 24 hours after single administration of BI 860585
|
Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585.
|
|
Half Life of BI 860585 (t1/2)
Prazo: Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585.
|
t ½, half-life of BI 860585 in plasma over a dosing interval after single administration of BI 860585
|
Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585.
|
|
Maximum Measured Concentration of BI 860585 (Cmax)
Prazo: Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585.
|
Cmax, maximum measured concentration of BI 860585 in plasma over a dosing interval after single administration of BI 860585
|
Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585.
|
|
Time to Maximum Concentration of BI 860585 (Tmax)
Prazo: Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585.
|
Tmax, Time to maximum concentration of BI 860585 in plasma over a dosing interval after single administration of BI 860585
|
Pharmacokinetic samples were collected at pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 23.917 hours after administration of BI 860585.
|
|
Area Under the Concentration-time Curve of BI 860585 in Plasma Over a Dosing Interval at Steady State (AUCτ,ss)
Prazo: Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
|
AUCτ,ss, area under the concentration-time curve of BI 860585 in plasma over the dosing interval at steady state after multiple administration of BI 860585 (Day 22) in BI 860585 monotherapy and in combination with exemestane and paclitaxel.
|
Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
|
|
Half Life of BI 860585 at Steady State (t1/2,ss)
Prazo: Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
|
t1/2,ss, half-life of BI 860585 in plasma at steady state after multiple administration of BI 860585 (Day 22) in BI 860585 monotherapy and in combination with exemestane and paclitaxel.
|
Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
|
|
Time to Maximum Concentration of BI 860585 at Steady State (Tmax,ss)
Prazo: Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
|
tmax,ss, Time to maximum concentration of BI 860585 at steady state after multiple administration of BI 860585 (Day 22) in BI 860585 monotherapy and in combination with exemestane and paclitaxel.
|
Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
|
|
Maximum Measured Concentration of BI 860585 in Plasma at Steady State (Cmax,ss)
Prazo: Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
|
Cmax,ss, maximum measured concentration at steady state after multiple administration of BI 860585 (Day 22) in BI 860585 monotherapy and in combination with exemestane and paclitaxel.
|
Pharmacokinetic samples were collected at pre-dose and at 504.5, 505, 506, 507, 508, 510, 512, 527.917 hours after drug administration.
|
Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
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)
5 de setembro de 2013
Conclusão Primária (Real)
30 de julho de 2016
Conclusão do estudo (Real)
22 de junho de 2017
Datas de inscrição no estudo
Enviado pela primeira vez
5 de setembro de 2013
Enviado pela primeira vez que atendeu aos critérios de CQ
5 de setembro de 2013
Primeira postagem (Estimativa)
10 de setembro de 2013
Atualizações de registro de estudo
Última Atualização Postada (Real)
4 de janeiro de 2019
Última atualização enviada que atendeu aos critérios de controle de qualidade
19 de junho de 2018
Última verificação
1 de junho de 2018
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Agentes Antineoplásicos
- Moduladores de Tubulina
- Agentes Antimitóticos
- Moduladores de Mitose
- Hormônios, Substitutos Hormonais e Antagonistas Hormonais
- Agentes Antineoplásicos Fitogênicos
- Antagonistas Hormonais
- Inibidores de Aromatase
- Inibidores da Síntese de Esteróides
- Antagonistas de Estrogênio
- Paclitaxel
- Exemestano
Outros números de identificação do estudo
- 1325.1
- 2013-000765-36 (Número EudraCT)
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 .
Ensaios clínicos em BI 860585
-
Boehringer IngelheimConcluído
-
Boehringer IngelheimConcluído
-
Boehringer IngelheimConcluído
-
Boehringer IngelheimConcluído
-
Boehringer IngelheimAtivo, não recrutandoMelanoma | Câncer de Pulmão de Células Não Pequenas (NSCLC) | Carcinoma de Células Escamosas de Cabeça e Pescoço (HNSCC)Holanda
-
Boehringer IngelheimConcluído
-
Boehringer IngelheimConcluído
-
Boehringer IngelheimConcluído
-
Boehringer IngelheimConcluído