- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT01042925
Study of XL147 (SAR245408) in Combination With Trastuzumab or Paclitaxel and Trastuzumab in Subjects With Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-based Regimen
A Phase 1/2 Study of XL147 (SAR245408) Administered in Combination With Trastuzumab or Paclitaxel and Trastuzumab in Subjects With Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-Based Regimen
Phase 1 of this study will evaluate the maximum tolerated dose (MTD) of XL147 when given in combination with trastuzumab (Herceptin) and in combination with trastuzumab and paclitaxel. After the MTD is established for each combination (Phase 2), subjects will be enrolled to evaluate the preliminary efficacy and safety of these combinations in metastatic HER2 positive breast cancer. Both trastuzumab and paclitaxel are used in the treatment of metastatic breast cancer (MBC), but patients can develop resistance.
The link between PI3K mutations and trastuzumab resistance has been seen in breast cancer patients. This suggests that inhibitors of the PI3K/PTEN pathway may have the potential to restore sensitivity to trastuzumab. Similarly, introduction of activated mutant forms of PI3K has been shown to transform and confer paclitaxel resistance to immortalized breast epithelial cells. XL147 is a potent and selective inhibitor of PI3K and inhibits phosphorylation of multiple downstream components of PI3K/PTEN signaling. Therefore, XL147 may have utility in the treatment of trastuzumab resistant/refractory and HER2-positive MBC when administered in combination with trastuzumab alone or with trastuzumab and paclitaxel.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
- Fase 1
Contactos e Locais
Locais de estudo
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Madrid, Espanha, 28041
- Investigational Site Number 3413
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California
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Los Angeles, California, Estados Unidos, 90033
- Investigational Site Number 1537
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Florida
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Fort Meyers, Florida, Estados Unidos, 33901
- Investigational Site Number 1238
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02115
- Investigational Site Number 1138
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Michigan
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Detroit, Michigan, Estados Unidos, 48201
- Investigational Site Number 1330
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New York
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Bronx, New York, Estados Unidos, 10467
- Investigational Site Number 1151
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New York, New York, Estados Unidos, 10032
- Investigational Site Number 1150
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37203
- Investigational Site Number 1214
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Nashville, Tennessee, Estados Unidos, 37232
- Investigational Site Number 1246
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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:
- The subject has pathologically and radiologically confirmed metastatic HER2 positive breast cancer (Stage IV disease). Subjects must have received and progressed on at least one prior trastuzumab-containing regimen for metastatic disease. For subjects in Arm 2, they must also have received at least one prior taxane-containing regimen.
- The subject has at least one lesion that is not within a previously radiated field and measurable on computerized tomography (CT) or magnetic resonance imaging scan (MRI)
- The subjects enrolled in Phase 2 must be willing to undergo a biopsy of the primary tumor or a tumor metastasis at baseline, if tumor tissue is amenable to biopsy
- The subject's primary tumor and/or metastatic lesion must overexpress HER2
- For subjects enrolled in Phase 2: samples from archival or fresh tissue, or a tissue block of the subject's tumor.
- The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- The subject has adequate organ and marrow function
- The subject is capable of understanding the informed consent and complying with the protocol and has signed the informed consent document prior to any study-specific screening procedures or evaluations being performed.
- Sexually active subjects must agree to use a medically-accepted barrier method of contraception during the course of the study and for 3 months following discontinuation of study treatments. For subjects using oral contraceptives, a barrier method must be used in addition to the oral contraceptive
- Subjects of childbearing potential must have a negative pregnancy test at screening and enrollment
Exclusion Criteria:
- The subject has previously been treated with a selective inhibitor of PI3K and / or AKT
- Certain restrictions on prior therapies apply
- The subject has not recovered from toxicity due to prior therapy to Grade ≤ 1 or to pre-therapy baseline
- The subject has untreated, symptomatic, or progressive brain metastases. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥4 weeks prior to first study treatment
- The subject has prothrombin time/International Normalized Ratio (PT/INR) or partial thromboplastin time (PTT) test results at screening that are ≥ 1.3 times above the laboratory upper limit of normal
- The subject has a diagnosis of uncontrolled diabetes mellitus
- The subject has uncontrolled significant intercurrent illness
- The subject has uncontrolled hypertension or other clinically significant cardiovascular disease
- The subject has left ventricular ejection fraction (LVEF) ≤ 50%
- The subject has a baseline corrected QT interval ≥ 460 ms
- The subject is currently receiving anticoagulation with therapeutic doses of warfarin (low-dose warfarin ≤ 1mg/day is permitted)
- The subject is pregnant or breastfeeding
- The subject is known to be positive for the human immunodeficiency virus (HIV) (a test for HIV at screening is not required)
- The subject has any other diagnosis of malignancy or evidence of malignancy (except non-melanoma skin cancer, in situ carcinoma of the cervix) within 2 years prior to screening for this study
- The subject has a previously identified allergy or hypersensitivity or is intolerant to components of any of the study treatment formulations
- The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
Plano de estudo
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 |
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Experimental: Arm 1
XL147 in combination with trastuzumab
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administered orally once daily as tablet(s)
administered by IV once every 3 weeks
Outros nomes:
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Experimental: Arm 2
XL147 in combination with trastuzumab and paclitaxel
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administered orally once daily as tablet(s)
administered by IV once every 3 weeks
Outros nomes:
administered by IV once every week
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
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Safety and tolerability of XL147 in combination with trastuzumab and in combination with trastuzumab and paclitaxel
Prazo: safety assessments at weekly study visits
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safety assessments at weekly study visits
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In Phase 1, the maximum tolerated dose (MTD) of XL147 when administered in combination with trastuzumab and in combination with trastuzumab and paclitaxel
Prazo: assessed by weekly study visits
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assessed by weekly study visits
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In Phase 2, objective tumor response
Prazo: every 6 weeks
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every 6 weeks
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Medidas de resultados secundários
Medida de resultado |
Prazo |
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Duration of response and progression-free survival (Phase 2)
Prazo: every 6 weeks
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every 6 weeks
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Pharmacokinetics and pharmacodynamics of XL147 and trastuzumab when given in combination, and of XL147, trastuzumab, and paclitaxel when given in combination
Prazo: assessed weekly, then every 3 weeks
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assessed weekly, then every 3 weeks
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Colaboradores e Investigadores
Patrocinador
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
Termos MeSH relevantes adicionais
- Doenças de pele
- Neoplasias
- Neoplasias por local
- Doenças da mama
- Neoplasias da Mama
- Mecanismos Moleculares de Ação Farmacológica
- Agentes Antineoplásicos
- Moduladores de Tubulina
- Agentes Antimitóticos
- Moduladores de Mitose
- Agentes Antineoplásicos Fitogênicos
- Agentes Antineoplásicos Imunológicos
- Paclitaxel
- Trastuzumabe
Outros números de identificação do estudo
- ARD11439
- XL147-203 (Outro identificador: (other study code))
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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Turku University HospitalLounais-Suomen SyöpäyhdistysAinda não está recrutandoSobrevivente de cancerFinlândia
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Roswell Park Cancer InstituteNational Cancer Institute (NCI)RetiradoSobrevivente de cancerEstados Unidos
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Wake Forest University Health SciencesNational Cancer Institute (NCI)ConcluídoSobrevivente de cancerEstados Unidos, Guam
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Wake Forest University Health SciencesNational Cancer Institute (NCI); National Institute of Mental Health (NIMH)ConcluídoSobrevivente de cancerEstados Unidos
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Masonic Cancer Center, University of MinnesotaConcluídoSobrevivente de cancerEstados Unidos
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University of New MexicoNew Mexico State University; University of New Mexico Cancer CenterConcluído
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Ohio State University Comprehensive Cancer CenterConcluídoSobrevivente de cancerEstados Unidos
Ensaios clínicos em XL147 (SAR245408)
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SanofiConcluídoNeoplasias endometriais | Câncer do endométrioEstados Unidos, Bélgica
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SanofiConcluídoEstudo da Segurança e Farmacocinética de XL147 (SAR245408) em Adultos com Tumores Sólidos ou LinfomaLinfoma | CâncerEstados Unidos, Espanha
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SanofiConcluídoTumores SólidosEstados Unidos
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SanofiConcluídoGlioblastoma | Astrocitoma, Grau IVEstados Unidos
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SanofiConcluídoCâncer | Câncer de Pulmão de Células Não Pequenas | Carcinoma Endometrial | Carcinoma de OvárioEstados Unidos
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SanofiConcluído
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SanofiConcluídoNeoplasia MalignaJapão
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SanofiConcluídoCâncer de mamaEstados Unidos, França, Espanha
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SanofiConcluídoNeoplasia MalignaEspanha, Bélgica, Estados Unidos, França
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SanofiMerrimack PharmaceuticalsConcluídoCânceres de Tumores SólidosEstados Unidos