Ruxolitinib in Patients With Breast Cancer
3 de janeiro de 2017 atualizado por: Nancy Lin, MD, Dana-Farber Cancer Institute
Phase II Study of Ruxolitinib (INCB018424) in Patients With PSTAT3+ Breast Cancer
Ruxolitinib is a drug which blocks the Janus tyrosine Kinase (JAK) signaling pathway.
It is thought that this pathway might be important in certain types of breast cancer, and that blocking this pathway might lead to anti-cancer effects.
This study is testing the effects of ruxolitinib in patients with breast cancer.
Visão geral do estudo
Descrição detalhada
Objectives:
Primary
- The primary objective of this two-stage, phase II study is to estimate the objective response rate to ruxolitinib in patients with metastatic or unresectable locally advanced breast cancer which is pStat3+ and which has progressed on at least one line of chemotherapy for advanced disease, and/or has recurred within 12 months of completion of neoadjuvant/adjuvant chemotherapy.
Secondary
- To describe the toxicity profile
- To evaluate clinical benefit rate (CR + PR + SD >/= 24 weeks)
- To estimate progression-free and overall survival
Exploratory
- To explore whether baseline hs-CRP level higher than the group median is associated with objective response
- To explore whether baseline IL-6 level higher than the group median is associated with objective response
- To describe hs-CRP level over time, and to describe the proportion of patients with a) hs-CRP > 3mg/L at baseline, on treatment, and at time of progression, and b) hs-CRP > 1mg/L at baseline, on treatment, and at time of progression
- To describe IL-6 level over time, and to describe the proportion of patients with IL-6 level above the upper limit of normal at baseline, on treatment, and at time of progression
- To describe pStat3 status by IHC in baseline metastatic biopsies
- To describe pStat3 status by IHC in on-study biopsies
- To describe pStat3 status by IHC in the time of progression biopsy samples
- To characterize archival and metastatic biopsy samples using triple immunofluorescence for CD44, CD24, and pStat3
- To characterize archival and metastatic biopsy samples using a previously characterized pStat3 gene signature
- To characterize circulating tumor cells (CTCs) for CD44, CD24, and pStat3 at baseline and time of progression
Tipo de estudo
Intervencional
Inscrição (Real)
21
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
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital
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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:
- Histologically or cytologically confirmed invasive breast cancer
- Must have known ER, PR and HER2 status
- Either, Triple Negative Metastatic Breast Cancer or
- Inflammatory Breast Cancer with any ER, PR HER2 status
- Availability of archival tissue specimen suitable for pStat3 testing
- Life expectancy of greater than 3 months
- Measurable disease by RECIST
- At least one prior chemotherapy regimen for treatment of metastatic breast cancer and/or recurrence within 12 months of completion of neoadjuvant/adjuvant chemotherapy or
- For patients with inflammatory breast cancer but no distant metastases, progression through standard neoadjuvant chemotherapy is required
Exclusion Criteria:
- Pregnant or breastfeeding
- Active brain metastases
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib
- Clinically significant malabsorption syndrome
- Concurrent use of medications/substances that are strong inhibitors of CY3A4
- No uncontrolled intercurrent illness
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: Ruxolitinib-Cohort A
Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity.
Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of >/=5 by central testing or Cohort B - low positive status defined as a score of 3-4.
Each cohort was evaluated with a 2 stage design.
Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
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Outros nomes:
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Experimental: Ruxolitinib-Cohort B
Patients received Ruxolitinib 25 mg twice daily for up to 12 cycles (cycle duration=28 days) until evidence of disease progression or unacceptable toxicity.
Patients enrolled sequentially into two possible cohorts based on pStat3+ expression score by central testing: Cohort A - moderate to high positive status defined as a score of >/=5 by central testing or Cohort B - low positive status defined as a score of 3-4.
Each cohort was evaluated with a 2 stage design.
Cohort B only opened if 2 objective responses were observed in 1st stage Cohort A patients (n=21).
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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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Objective Response Rate
Prazo: Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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The objective response rate (ORR) was defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment.
Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
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Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Clinical Benefit Rate
Prazo: Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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Clinical benefit rate (CBR) was defined as achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment.
Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions.
Stable disease (SD) is defined as any condition not meeting the above criteria.
SD needed to be a minimum 24 weeks in duration.
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Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity up to 12 cycles. Treatment duration was a median of 2 cycles range (1-5).
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Overall Survival
Prazo: In long-term follow-up, patients were followed for survival every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.
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In long-term follow-up, patients were followed for survival every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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Progression-Free Survival
Prazo: Disease was evaluated radiologically every 8 weeks on treatment through 12 cycles and in long-term follow-up every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death.
Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or equivocal progression of non-target lesions.
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Disease was evaluated radiologically every 8 weeks on treatment through 12 cycles and in long-term follow-up every 4 months for up to 2 years. Median follow-up in this study cohort was 4.5 months (range 0.6-21.9).
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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
1 de junho de 2012
Conclusão Primária (Real)
1 de junho de 2015
Conclusão do estudo (Real)
1 de junho de 2016
Datas de inscrição no estudo
Enviado pela primeira vez
20 de março de 2012
Enviado pela primeira vez que atendeu aos critérios de CQ
22 de março de 2012
Primeira postagem (Estimativa)
26 de março de 2012
Atualizações de registro de estudo
Última Atualização Postada (Real)
23 de fevereiro de 2017
Última atualização enviada que atendeu aos critérios de controle de qualidade
3 de janeiro de 2017
Última verificação
1 de janeiro de 2017
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 12-024
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
NÃO
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