- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT00546104
Phase II Dasatinib Study in Advanced Breast Cancer
A Phase II Trial of Dasatinib to Treat Women With Stage IV or Inoperable Stage III Advanced Breast Cancer
Visão geral do estudo
Descrição detalhada
The introduction of biologics with specific molecular targets has initiated a trend toward improved survival in women with metastatic breast cancer.
The tyrosine kinase SRC (pp60src) is a member of a family of proteins that contribute to cellular signal transduction activities such as cell growth, differentiation, survival, adhesion and migration. Abnormal signaling has been linked to cancer metastases; thus, identification of molecular regulators or inhibitors of SRC present therapeutic opportunity for cancer patients. Src kinases consist of eight non-receptor tyrosine kinases (Src, Fyn, Yes, Lck, Lyn, Hck, Fgr and Blk) that interact with the intracellular domains of growth factor/cytokine receptors, (G-protein-coupled receptor)GPCRs and integrins.
Inhibition of SRC has also been associated with reversal of chemoresistance and restored sensitivity to drug-resistant ovarian cancer cells, suggesting potential as second- line treatment for previously treated populations. Dasatinib is a potent, broad spectrum inhibitor of 5 critical oncogenic tyrosine kinases, including SRC.
Patients will receive dasatinib, a Src inhibitor, at an initial dose of 50 mg PO BID, with real-time PharmacoDynamic dose adjustment following 4 weeks of therapy based on inhibition of phosphorylation of SRC, focal adhesion kinase (FAK) and paxillin, until progression. The primary objective is to assess tolerability and estimate the proportion of patients who are progression-free at 16 weeks from the date of study enrollment.
A minimum of 2 (maximum of 3) tumor biopsies will be analyzed and compared for SRC signature: one at baseline (study enrollment, all patients); the second after 4 weeks of dasatinib therapy (all patients); and the third at progression (only patients who progress after a documented response).
Patients will receive continuous daily administration until documented disease progression, and will be followed until death.
The results of this study may be useful in designing future studies using dasatinib alone or in combination with chemotherapy, thus having the potential to alter the current standard of care in this incurable population.
Additional correlative studies will be conducted. Tumor biopsies will be analyzed and compared for SRC, pSRC, Ki67, and related genomic signatures.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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Florida
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West Palm Beach, Florida, Estados Unidos, 33401
- Palm Beach Cancer Center Institute
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North Carolina
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Charlotte, North Carolina, Estados Unidos, 28204
- Presbyterian Health Care
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Durham, North Carolina, Estados Unidos, 27710
- Duke University Medical Center
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Measurable Stage IV or inoperable Stage III advanced breast cancer.
- There is no limit on the number of prior therapies.
- At least 3 weeks since prior chemotherapy, biological or hormonal therapy.
- At least 2 weeks since surgical biopsy.
- At least 3 weeks since major (open thoracic/abdominal/cardiac) surgery.
- No central nervous system (CNS) metastases except solitary brain metastasis
- No cardiac dysfunction
- left ventricular ejection fraction (LVEF) ≥ 50% as determined by multiple gated acquisition scan (MUGA)/echocardiogram
- Adequate blood counts
- Normal liver and kidney function
- Negative serum pregnancy test.
- Able to provide informed consent
Exclusion Criteria:
- Pregnant or breast feeding.
- Prior treatment with dasatinib.
- Bone as the only site of disease.
- Significant gastrointestinal bleeding
- Septicemia, infection, acute hepatitis, hypokalemia, or hypomagnesemia
Plano de estudo
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 |
---|---|
Experimental: Dasatinib
50- 100 mg PO BID
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An initial dose of 50 mg PO BID; following 4 weeks of treatment, dose adjustment will be based on inhibition of phosphorylation of FAK and paxillin per biopsy assessment, as well as toxicity assessment.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Estimation of the Proportion of Progression-free Patients at 16 Wks.
Prazo: 16 weeks
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Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or measurable increase in a non-target lesion, or the appearance of new lesions, or similar definition as appropriate. Proportion progression-free at 16 weeks.From first day of study related treatment with Dasatinib until the date of first documented progression or date of death from any cause, whichever came first. |
16 weeks
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
To Measure Response to Protocol Therapy Per RECIST Criteria
Prazo: 16 weeks
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Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression At least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as a reference the smallest sum longest diameter recorded since treatment started, or the appearance of one or more new lesions. RECIST 1.0 Overall response: Complete Response (CR) Partial Response (PR) Stable Disease (SD) Progressive Disease (PD) CR= CR+CR and No new lesions PR= CR+SD; PR+SD and no new lesions SD= SD+SD and no new lesions PD= PD+any new lesions |
16 weeks
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Characterization and Comparison of SRC (A Protein Tyrosine Kinase)Dysregulation at Baseline (All Patients), After 4 Weeks of Dasatinib Treatment (All Patients), and at Progression (Only Patients Who Progress After Documented Response)
Prazo: 4 weeks
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For the 20 patients with evaluable biopsies at baseline and week 4, the median relative change from baseline in tissue biomarker levels of phospho-Src (p-Src)
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4 weeks
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Correlate SRC Dysregulation Results With Response to Dasatinib Therapy
Prazo: 16 weeks
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Since all patients progressed there is no comparison to between responders and non-responders.
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16 weeks
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To Explore the Association Between Each Patient's SRC Signature and Their Time to Progression.
Prazo: Baseline Src measure to first progression
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Spearman's correlation between the change in SRC signature from baseline to 4 weeks and time to progression
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Baseline Src measure to first progression
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To Explore the Association Between Dasatinib and Osteoclastic Bone Resorption
Prazo: not assessed
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Not assessed secondary to limited number of subjects.
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not assessed
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Kimberly Blackwell, MD, Duke University
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- Pro00007578
- BMS CA180089
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 .
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