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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 octubre de 2015 actualizado 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.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

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 estudio

Intervencionista

Inscripción (Actual)

228

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Australia
    • South Australia
      • Kurralta Park, South Australia, Australia, 5037
        • Research Site
    • Victoria
      • Epping, Victoria, Australia, 3076
        • Research Site
      • Fitzroy, Victoria, Australia, 3065
        • Research Site
      • Footscray, Victoria, Australia, 3011
        • Research Site
      • Malvern, Victoria, Australia, 3144
        • Research Site
    • Western Australia
      • Perth, Western Australia, Australia, 6000
        • Research Site
  • Austria
      • Innsbruck, Austria, 6020
        • Research Site
      • Wels, Austria, 4600
        • Research Site
      • Wien, Austria, 1090
        • Research Site
  • Bélgica
      • Leuven, Bélgica, 3000
        • Research Site
      • Liege, Bélgica, 4000
        • Research Site
      • Wilrijk, Bélgica, 2610
        • Research Site
  • Dinamarca
      • Herlev, Dinamarca, 2730
        • Research Site
  • España
      • Madrid, España, 28033
        • Research Site
    • AndalucÃ-a
      • Jaén, AndalucÃ-a, España, 23007
        • Research Site
    • Cataluña
      • Sabadell, Cataluña, España, 08208
        • Research Site
    • Galicia
      • Santiago de Compostela, Galicia, España, 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
  • Finlandia
      • Helsinki, Finlandia, 00029
        • Research Site
  • Francia
      • La Roche Sur Yon Cedex 9, Francia, 85925
        • Research Site
      • Lyon, Francia, 69008
        • Research Site
      • Marseille, Francia, 13009
        • Research Site
      • Montpellier Cedex 5, Francia, 34298
        • Research Site
      • Paris Cedex 20, Francia, 75020
        • Research Site
      • Paris Cedex 5, Francia, 75248
        • Research Site
      • Toulouse Cedex, Francia, 31052
        • Research Site
      • Vandoeuvre les Nancy, Francia, 54511
        • Research Site
  • Hungría
      • Gyula, Hungría, 5700
        • Research Site
      • Kaposvar, Hungría, 7400
        • Research Site
      • Szombathely, Hungría, 9700
        • Research Site
      • Veszprem, Hungría, 8200
        • Research Site
  • India
    • Karnataka
      • Bangalore, Karnataka, India, 560 029
        • Research Site
    • Maharashtra
      • Miraj, Maharashtra, India, 416 410
        • Research Site
      • Mumbai, Maharashtra, India, 400 012
        • Research Site
      • Nagpur, Maharashtra, India, 440 012
        • Research Site
      • Pune, Maharashtra, India, 411 001
        • Research Site
    • Rajasthan
      • Jaipur, Rajasthan, India, 302 013
        • Research Site
      • Jaipur, Rajasthan, India, 302 004
        • Research Site
  • Países Bajos
      • Maastricht, Países Bajos, 6229 HX
        • Research Site
  • Polonia
      • Gdansk, Polonia, 80-952
        • Research Site
      • Lubin, Polonia, 59-300
        • Research Site
      • Poznan, Polonia, 61-485
        • Research Site
      • Warszawa, Polonia, 02-781
        • Research Site
      • Warszawa, Polonia, 04-141
        • Research Site
      • Wroclaw, Polonia, 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

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

Sí

Géneros elegibles para el estudio

Femenino

Descripción

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

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
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
Droga: AMG 386
AMG 386 3mg/kg IV QW [blinded]
Droga: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Droga: AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
Droga: AMG 386
AMG 386 10mg/kg IV QW [blinded]
Droga: 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
Droga: AMG 386
AMG 386 3mg/kg IV QW [blinded]
Droga: AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
Droga: AMG 386
AMG 386 10mg/kg IV QW [blinded]
Droga: 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
Droga: AMG 386
AMG 386 3mg/kg IV QW [blinded]
Droga: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Droga: AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
Droga: AMG 386
AMG 386 10mg/kg IV QW [blinded]
Droga: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Comparador activo: C
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW
Droga: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Droga: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Droga: AMG 386 Placebo
AMG 386 Placebo [blinded]

¿Qué mide el estudio?

Medidas de resultado primarias

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

Medidas de resultado secundarias

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

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Amgen

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Enlaces Útiles

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de julio de 2007

Finalización primaria (Actual)

1 de agosto de 2010

Finalización del estudio (Actual)

1 de mayo de 2014

Fechas de registro del estudio

Enviado por primera vez

2 de agosto de 2007

Primero enviado que cumplió con los criterios de control de calidad

2 de agosto de 2007

Publicado por primera vez (Estimar)

3 de agosto de 2007

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

29 de octubre de 2015

Última actualización enviada que cumplió con los criterios de control de calidad

7 de octubre de 2015

Última verificación

1 de octubre de 2015

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • 20060341

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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