Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

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

7. oktober 2015 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

228

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ja

Køn, der er berettiget til at studere

Kvinde

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: A
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW
Medicin: AMG 386
AMG 386 3mg/kg IV QW [blinded]
Medicin: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Medicin: AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
Medicin: AMG 386
AMG 386 10mg/kg IV QW [blinded]
Medicin: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Eksperimentel: D
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW
Medicin: AMG 386
AMG 386 3mg/kg IV QW [blinded]
Medicin: AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
Medicin: AMG 386
AMG 386 10mg/kg IV QW [blinded]
Medicin: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Eksperimentel: B
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 3 mg/kg IV QW
Medicin: AMG 386
AMG 386 3mg/kg IV QW [blinded]
Medicin: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Medicin: AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
Medicin: AMG 386
AMG 386 10mg/kg IV QW [blinded]
Medicin: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Aktiv komparator: C
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW
Medicin: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Medicin: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Medicin: AMG 386 Placebo
AMG 386 Placebo [blinded]

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Progression-free survival (PFS)
Tidsramme: 3 YEARS
3 YEARS

Sekundære resultatmål

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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Amgen

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. juli 2007

Primær færdiggørelse (Faktiske)

1. august 2010

Studieafslutning (Faktiske)

1. maj 2014

Datoer for studieregistrering

Først indsendt

2. august 2007

Først indsendt, der opfyldte QC-kriterier

2. august 2007

Først opslået (Skøn)

3. august 2007

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

29. oktober 2015

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

7. oktober 2015

Sidst verificeret

1. oktober 2015

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 20060341

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med AMG 386

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Myanmar

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner