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Phase 2 Study of AMG 386 Plus Paclitaxel With or Without Bevacizumab as First Line Therapy in Her2-Negative Breast Cancer Patients

7 de outubro de 2015 atualizado por: Amgen

A Randomized, 4-Arm, Placebo-Controlled Phase 2 Trial of AMG 386 in Combination With Bevacizumab and Paclitaxel or AMG 386 Plus Paclitaxel as First-Line Therapy in Subjects With Her2-Negative, Metastatic or Locally Recurrent Breast Cancer

This is a phase 2, randomized, placebo controlled, multi-center study to estimate the treatment effect and evaluate the safety and tolerability of AMG 386 in combination with paclitaxel and paclitaxel/bevacizumab in the treatment of subjects with Her2-negative metastatic or locally recurrent breast cancer.

AMG 386 is a man-made medication that is designed to stop the development of blood vessels in cancer tissues. Cancer tissues rely on the development of new blood vessels, a process called angiogenesis, to obtain a supply of oxygen and nutrients to grow.

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Descrição detalhada

Primary Objective: To estimate the treatment effect as measured by progression free survival (PFS) of subjects receiving AMG 386 (at 2 doses) in combination with paclitaxel + bevacizumab relative to paclitaxel + bevacizumab + placebo.

Secondary Objective(s):

  • To compare the treatment effect as measured by PFS of subjects receiving open-label AMG 386 in combination with paclitaxel relative to paclitaxel + bevacizumab + placebo
  • To compare the treatment effect as measured by PFS of subjects receiving AMG 386 in combination with paclitaxel and bevacizumab relative to paclitaxel + AMG 386
  • To evaluate the safety and tolerability of the combination and non-bevacizumab regimens
  • To estimate other measures (RR, DOR, TTR, TTP) of treatment effect
  • To evaluate the pharmacokinetics (PK) of AMG 386 and bevacizumab when used in combination
  • To estimate the incidence of anti-AMG386 antibody formation

Exploratory Objective(s):

  • To explore the pharmacodynamic (PD) response as assessed by changes in blood levels of angiogenic cytokines, tumor apoptosis, and other markers
  • To explore the association of histological features and selected immunologic, biochemical, pharmacogenetic, or angiogenic markers in tumor biopsies, plasma, or serum samples with safety and/or efficacy outcomes

Study Design:

This is a phase 2, randomized, placebo controlled, multi-center study to estimate the treatment effect and evaluate the safety and tolerability of AMG 386 in combination with paclitaxel and paclitaxel/bevacizumab in the treatment of subjects with Her2-negative metastatic or locally recurrent breast cancer.

Two hundred twenty subjects will be randomized 1:1:1:1 to each of the following arms:

Arm A: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW Arm B: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 3 mg/kg IV QW Arm C: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW Arm D: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW To maintain the double-blind in arms A, B, and C, each subject will be infused weekly with a volume of investigational product equivalent to 10 mg/kg AMG 386 IV. Arm D will receive open label AMG 386 and will not receive a placebo for bevacizumab.

Subjects will be discontinued from study treatment at any time for radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death.

Subjects alive at the time of discontinuation of all study medications will be followed for up to 48 months from the date of the last subject enrolled into the trial to evaluate overall survival.

Radiological imaging to assess disease status will be performed every 8 weeks ± 7 days (2 cycles) for 2 years and then every 4 months ± 1 month thereafter during the study until subjects develop radiographic disease progression per the modified RECIST criteria. In addition, any subject who discontinues study drug treatment prior to disease progression will continue to have radiological imaging performed every 8 weeks ± 7 days during the long term follow up period if the subject has not been in the study for 2 years until the subject develops radiographic disease progression or begins a new treatment. If the subject has been on study for 2 years, radiological imaging every 4 months ± 1 month will be performed during long term follow-up period until the subject develops radiographic disease progression or begins a new treatment.

The overall study design is described by a study schema immediately following this synopsis. Amgen Global Safety (AGS) will charter a data review team (DRT) that is independent of the team conducting the study and will review unblinded safety data after 20, 40, and 80 subjects have been randomized and have had the opportunity to receive at least 1 cycle (4 weeks) of study treatment.

Tipo de estudo

Intervencional

Inscrição (Real)

228

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

  • Austrália
    • South Australia
      • Kurralta Park, South Australia, Austrália, 5037
        • Research Site
    • Victoria
      • Epping, Victoria, Austrália, 3076
        • Research Site
      • Fitzroy, Victoria, Austrália, 3065
        • Research Site
      • Footscray, Victoria, Austrália, 3011
        • Research Site
      • Malvern, Victoria, Austrália, 3144
        • Research Site
    • Western Australia
      • Perth, Western Australia, Austrália, 6000
        • Research Site
  • Bélgica
      • Leuven, Bélgica, 3000
        • Research Site
      • Liege, Bélgica, 4000
        • Research Site
      • Wilrijk, Bélgica, 2610
        • Research Site
  • Dinamarca
      • Herlev, Dinamarca, 2730
        • Research Site
  • Espanha
      • Madrid, Espanha, 28033
        • Research Site
    • AndalucÃ-a
      • Jaén, AndalucÃ-a, Espanha, 23007
        • Research Site
    • Cataluña
      • Sabadell, Cataluña, Espanha, 08208
        • Research Site
    • Galicia
      • Santiago de Compostela, Galicia, Espanha, 15706
        • Research Site
  • Estados Unidos
    • Arizona
      • Litchfield Park, Arizona, Estados Unidos, 85340
        • Research Site
      • Tucson, Arizona, Estados Unidos, 85724
        • Research Site
    • Arkansas
      • Hot Springs, Arkansas, Estados Unidos, 71913
        • Research Site
      • Little Rock, Arkansas, Estados Unidos, 72205
        • Research Site
    • California
      • Campbell, California, Estados Unidos, 95008
        • Research Site
      • Los Angeles, California, Estados Unidos, 90095
        • Research Site
      • Murrieta, California, Estados Unidos, 92562
        • Research Site
      • Santa Maria, California, Estados Unidos, 93454
        • Research Site
    • Connecticut
      • New Haven, Connecticut, Estados Unidos, 06520
        • Research Site
      • Stamford, Connecticut, Estados Unidos, 06902
        • Research Site
    • Florida
      • Orlando, Florida, Estados Unidos, 32804
        • Research Site
    • Minnesota
      • Robbinsdale, Minnesota, Estados Unidos, 55422
        • Research Site
    • Nevada
      • Henderson, Nevada, Estados Unidos, 89052
        • Research Site
    • New Hampshire
      • Lebanon, New Hampshire, Estados Unidos, 03756
        • Research Site
      • Nashua, New Hampshire, Estados Unidos, 03061
        • Research Site
    • New Jersey
      • Edison, New Jersey, Estados Unidos, 08820
        • Research Site
      • Mountain Lakes, New Jersey, Estados Unidos, 07046
        • Research Site
    • North Carolina
      • Asheville, North Carolina, Estados Unidos, 28806
        • Research Site
      • Charlotte, North Carolina, Estados Unidos, 28203
        • Research Site
    • Pennsylvania
      • Hershey, Pennsylvania, Estados Unidos, 17033
        • Research Site
      • Philadelphia, Pennsylvania, Estados Unidos, 19106
        • Research Site
    • South Carolina
      • Columbia, South Carolina, Estados Unidos, 29210
        • Research Site
    • Texas
      • Richardson, Texas, Estados Unidos, 75080
        • Research Site
      • San Antonio, Texas, Estados Unidos, 78229
        • Research Site
      • Sugar Land, Texas, Estados Unidos, 77479
        • Research Site
    • Utah
      • Ogden, Utah, Estados Unidos, 84403
        • Research Site
  • Finlândia
      • Helsinki, Finlândia, 00029
        • Research Site
  • França
      • La Roche Sur Yon Cedex 9, França, 85925
        • Research Site
      • Lyon, França, 69008
        • Research Site
      • Marseille, França, 13009
        • Research Site
      • Montpellier Cedex 5, França, 34298
        • Research Site
      • Paris Cedex 20, França, 75020
        • Research Site
      • Paris Cedex 5, França, 75248
        • Research Site
      • Toulouse Cedex, França, 31052
        • Research Site
      • Vandoeuvre les Nancy, França, 54511
        • Research Site
  • Holanda
      • Maastricht, Holanda, 6229 HX
        • Research Site
  • Hungria
      • Gyula, Hungria, 5700
        • Research Site
      • Kaposvar, Hungria, 7400
        • Research Site
      • Szombathely, Hungria, 9700
        • Research Site
      • Veszprem, Hungria, 8200
        • Research Site
  • Polônia
      • Gdansk, Polônia, 80-952
        • Research Site
      • Lubin, Polônia, 59-300
        • Research Site
      • Poznan, Polônia, 61-485
        • Research Site
      • Warszawa, Polônia, 02-781
        • Research Site
      • Warszawa, Polônia, 04-141
        • Research Site
      • Wroclaw, Polônia, 53-413
        • Research Site
  • Reino Unido
      • Guildford, Reino Unido, GU2 7XX
        • Research Site
      • Leicester, Reino Unido, LE1 5WW
        • Research Site
      • London, Reino Unido, W6 8RF
        • Research Site
      • London, Reino Unido, NW1 2PG
        • Research Site
      • Manchester, Reino Unido, M20 4BX
        • Research Site
      • Northwood, Reino Unido, HA6 2RN
        • Research Site
      • Nottingham, Reino Unido, NG5 1PB
        • Research Site
  • Áustria
      • Innsbruck, Áustria, 6020
        • Research Site
      • Wels, Áustria, 4600
        • Research Site
      • Wien, Áustria, 1090
        • Research Site
  • Índia
    • Karnataka
      • Bangalore, Karnataka, Índia, 560 029
        • Research Site
    • Maharashtra
      • Miraj, Maharashtra, Índia, 416 410
        • Research Site
      • Mumbai, Maharashtra, Índia, 400 012
        • Research Site
      • Nagpur, Maharashtra, Índia, 440 012
        • Research Site
      • Pune, Maharashtra, Índia, 411 001
        • Research Site
    • Rajasthan
      • Jaipur, Rajasthan, Índia, 302 013
        • Research Site
      • Jaipur, Rajasthan, Índia, 302 004
        • Research Site

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

Sim

Gêneros Elegíveis para o Estudo

Fêmea

Descrição

Inclusion Criteria:

  • Subjects must have histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
  • Measurable or non-measurable disease per modified RECIST guidelines
  • ECOG of 0 or 1 (within 14 days prior to randomization)

  • Adequate organ and hematological function as evidenced by the following laboratory studies within 14 days prior to randomization:

    • Cardiac function, as follows:

  • Normal sinus rhythm (no significant ECG changes)
  • Left ventricular ejection fraction ≥ LLN, as determined by echocardiogram or MUGA scan, according to institutional standards within 28 days prior to randomization

Exclusion Criteria:

  • Inflammatory Breast Cancer
  • Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 peripheral neuropathy > grade 1 at randomization
  • History of arterial or venous thrombosis, including transient ischemic attack (TIA), within 1 year prior to randomization
  • Adjuvant or neoadjuvant taxane treatment within 12 months of randomization. Any other adjuvant chemotherapy regimen must be discontinued at least 21 days prior to randomization
  • Prior chemotherapy, vaccine, or biological therapy for locally recurrent or metastatic breast cancer (prior endocrine therapy is permitted)
  • Prior radiation therapy, radiofrequency ablation, percutaneous cryotherapy or hepatic chemoembolization on all sites of disease unless disease progression was subsequently documented 14 days prior to randomization.
  • Overexpression of HER-2 (gene amplification by FISH or 3+ over expression by immunohistochemistry).
  • Current or prior history of central nervous system metastasis
  • History of bleeding diathesis or clinically significant bleeding within 6 months prior to randomization
  • Major surgical procedure within 28 days prior to randomization
  • Open breast biopsy within 14 days prior to randomization
  • Minor surgical procedure, placement of access device, or fine needle aspiration within 7 days of first dose
  • Prior malignancy (other than thyroid cancer, in situ cervical cancer, or basal cell cancer of the skin, treated with curative intent and without evidence of disease for ≥ 3 years prior to randomization)
  • Clinically significant cardiac disease within 12 months prior to randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication
  • Non-healing wound, ulcer or fracture
  • Known hypersensitivity to paclitaxel or drugs using the vehicle cremophor
  • Known hypersensitivity to bacterial proteins, or any of the drugs required in this study
  • Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen
  • Known active or chronic hepatitis
  • Uncontrolled hypertension as defined as systolic blood pressure ≥ 150 mm Hg and diastolic blood pressure ≥ 90 mm Hg. Anti-hypertensive medications are allowed if the subject is stable on their current dose at the time of randomization
  • Currently or previously treated with any VEGF or VEGFr inhibitor, including but not limited to, bevacizumab, SU11248 (sunitinib), PTK787 (vatalinib), AZD 2171, AEE-788, BAY 43-9006 (sorafenib) and AMG 706.
  • Treatment with coumarin-type anticoagulants, (other than low dose prophylaxis for central venous catheters ≤ 1mg/day) within 7 days prior to randomization
  • Currently or previously treated with angiopoietin inhibitors, or inhibitors of TIE-1 or TIE-2 including, but not limited to, AMG 386, XL880, XL820
  • Treatment with immune modulators such as cyclosporine and tacrolimus within 30 days prior to randomization
  • Concomitant therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators (SERMS), given for breast cancer prevention or for osteoporosis. Subjects must have discontinued these agents 28 days prior to randomization
  • Pregnant (ie, positive beta-human chorionic gonadotropin test) or is breast feeding

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: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Quadruplicar

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: A
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW
Medicamento: AMG 386
AMG 386 3mg/kg IV QW [blinded]
Medicamento: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Medicamento: AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
Medicamento: AMG 386
AMG 386 10mg/kg IV QW [blinded]
Medicamento: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Experimental: D
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW
Medicamento: AMG 386
AMG 386 3mg/kg IV QW [blinded]
Medicamento: AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
Medicamento: AMG 386
AMG 386 10mg/kg IV QW [blinded]
Medicamento: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Experimental: B
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 3 mg/kg IV QW
Medicamento: AMG 386
AMG 386 3mg/kg IV QW [blinded]
Medicamento: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Medicamento: AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
Medicamento: AMG 386
AMG 386 10mg/kg IV QW [blinded]
Medicamento: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Comparador Ativo: C
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW
Medicamento: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Medicamento: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Medicamento: AMG 386 Placebo
AMG 386 Placebo [blinded]

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Prazo
Progression-free survival (PFS)
Prazo: 3 YEARS
3 YEARS

Medidas de resultados secundários

Medida de resultado
Prazo
Objective Response (OR)
Prazo: 3 YEARS
3 YEARS
Duration of Response (DOR)
Prazo: 3 YEARS
3 YEARS
Time to response
Prazo: 3 YEARS
3 YEARS
Overall Survival
Prazo: 3 YEARS
3 YEARS
Time to progression (TTP)
Prazo: 3 YEARS
3 YEARS
Incidence of AEs and significant laboratory changes
Prazo: 3 YEARS
3 YEARS
AMG 386 Pharmakokinetic parameters
Prazo: 3 YEARS
3 YEARS
Incidence of the occurrence of anti-AMG 386 antibody formation
Prazo: 3 YEARS
3 YEARS

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Amgen

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.

Publicações Gerais

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

1 de julho de 2007

Conclusão Primária (Real)

1 de agosto de 2010

Conclusão do estudo (Real)

1 de maio de 2014

Datas de inscrição no estudo

Enviado pela primeira vez

2 de agosto de 2007

Enviado pela primeira vez que atendeu aos critérios de CQ

2 de agosto de 2007

Primeira postagem (Estimativa)

3 de agosto de 2007

Atualizações de registro de estudo

Última Atualização Postada (Estimativa)

29 de outubro de 2015

Última atualização enviada que atendeu aos critérios de controle de qualidade

7 de outubro de 2015

Última verificação

1 de outubro de 2015

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • 20060341

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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