Denne siden ble automatisk oversatt og nøyaktigheten av oversettelsen er ikke garantert. Vennligst referer til engelsk versjon 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 oppdatert av: 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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert 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.

Studietype

Intervensjonell

Registrering (Faktiske)

228

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • 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
  • Belgia
      • Leuven, Belgia, 3000
        • Research Site
      • Liege, Belgia, 4000
        • Research Site
      • Wilrijk, Belgia, 2610
        • Research Site
  • Danmark
      • Herlev, Danmark, 2730
        • Research Site
  • Finland
      • Helsinki, Finland, 00029
        • Research Site
  • Forente stater
    • Arizona
      • Litchfield Park, Arizona, Forente stater, 85340
        • Research Site
      • Tucson, Arizona, Forente stater, 85724
        • Research Site
    • Arkansas
      • Hot Springs, Arkansas, Forente stater, 71913
        • Research Site
      • Little Rock, Arkansas, Forente stater, 72205
        • Research Site
    • California
      • Campbell, California, Forente stater, 95008
        • Research Site
      • Los Angeles, California, Forente stater, 90095
        • Research Site
      • Murrieta, California, Forente stater, 92562
        • Research Site
      • Santa Maria, California, Forente stater, 93454
        • Research Site
    • Connecticut
      • New Haven, Connecticut, Forente stater, 06520
        • Research Site
      • Stamford, Connecticut, Forente stater, 06902
        • Research Site
    • Florida
      • Orlando, Florida, Forente stater, 32804
        • Research Site
    • Minnesota
      • Robbinsdale, Minnesota, Forente stater, 55422
        • Research Site
    • Nevada
      • Henderson, Nevada, Forente stater, 89052
        • Research Site
    • New Hampshire
      • Lebanon, New Hampshire, Forente stater, 03756
        • Research Site
      • Nashua, New Hampshire, Forente stater, 03061
        • Research Site
    • New Jersey
      • Edison, New Jersey, Forente stater, 08820
        • Research Site
      • Mountain Lakes, New Jersey, Forente stater, 07046
        • Research Site
    • North Carolina
      • Asheville, North Carolina, Forente stater, 28806
        • Research Site
      • Charlotte, North Carolina, Forente stater, 28203
        • Research Site
    • Pennsylvania
      • Hershey, Pennsylvania, Forente stater, 17033
        • Research Site
      • Philadelphia, Pennsylvania, Forente stater, 19106
        • Research Site
    • South Carolina
      • Columbia, South Carolina, Forente stater, 29210
        • Research Site
    • Texas
      • Richardson, Texas, Forente stater, 75080
        • Research Site
      • San Antonio, Texas, Forente stater, 78229
        • Research Site
      • Sugar Land, Texas, Forente stater, 77479
        • Research Site
    • Utah
      • Ogden, Utah, Forente stater, 84403
        • Research Site
  • Frankrike
      • La Roche Sur Yon Cedex 9, Frankrike, 85925
        • Research Site
      • Lyon, Frankrike, 69008
        • Research Site
      • Marseille, Frankrike, 13009
        • Research Site
      • Montpellier Cedex 5, Frankrike, 34298
        • Research Site
      • Paris Cedex 20, Frankrike, 75020
        • Research Site
      • Paris Cedex 5, Frankrike, 75248
        • Research Site
      • Toulouse Cedex, Frankrike, 31052
        • Research Site
      • Vandoeuvre les Nancy, Frankrike, 54511
        • 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
  • Nederland
      • Maastricht, Nederland, 6229 HX
        • 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
  • Spania
      • Madrid, Spania, 28033
        • Research Site
    • AndalucÃ-a
      • Jaén, AndalucÃ-a, Spania, 23007
        • Research Site
    • Cataluña
      • Sabadell, Cataluña, Spania, 08208
        • Research Site
    • Galicia
      • Santiago de Compostela, Galicia, Spania, 15706
        • Research Site
  • Storbritannia
      • Guildford, Storbritannia, GU2 7XX
        • Research Site
      • Leicester, Storbritannia, LE1 5WW
        • Research Site
      • London, Storbritannia, W6 8RF
        • Research Site
      • London, Storbritannia, NW1 2PG
        • Research Site
      • Manchester, Storbritannia, M20 4BX
        • Research Site
      • Northwood, Storbritannia, HA6 2RN
        • Research Site
      • Nottingham, Storbritannia, NG5 1PB
        • Research Site
  • Ungarn
      • Gyula, Ungarn, 5700
        • Research Site
      • Kaposvar, Ungarn, 7400
        • Research Site
      • Szombathely, Ungarn, 9700
        • Research Site
      • Veszprem, Ungarn, 8200
        • Research Site
  • Østerrike
      • Innsbruck, Østerrike, 6020
        • Research Site
      • Wels, Østerrike, 4600
        • Research Site
      • Wien, Østerrike, 1090
        • Research Site

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Ja

Kjønn som er kvalifisert for studier

Hunn

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: A
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW
Legemiddel: AMG 386
AMG 386 3mg/kg IV QW [blinded]
Legemiddel: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Legemiddel: AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
Legemiddel: AMG 386
AMG 386 10mg/kg IV QW [blinded]
Legemiddel: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Eksperimentell: D
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW
Legemiddel: AMG 386
AMG 386 3mg/kg IV QW [blinded]
Legemiddel: AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
Legemiddel: AMG 386
AMG 386 10mg/kg IV QW [blinded]
Legemiddel: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Eksperimentell: B
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 3 mg/kg IV QW
Legemiddel: AMG 386
AMG 386 3mg/kg IV QW [blinded]
Legemiddel: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Legemiddel: AMG 386
AMG 386 10mg/kg IV QW [Open-Label]
Legemiddel: AMG 386
AMG 386 10mg/kg IV QW [blinded]
Legemiddel: 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
Legemiddel: Bevacizumab
Bevacizumab 10mg/kg IV Q2W
Legemiddel: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Legemiddel: AMG 386 Placebo
AMG 386 Placebo [blinded]

Hva måler studien?

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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Amgen

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Hjelpsomme linker

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. juli 2007

Primær fullføring (Faktiske)

1. august 2010

Studiet fullført (Faktiske)

1. mai 2014

Datoer for studieregistrering

Først innsendt

2. august 2007

Først innsendt som oppfylte QC-kriteriene

2. august 2007

Først lagt ut (Anslag)

3. august 2007

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

29. oktober 2015

Siste oppdatering sendt inn som oppfylte QC-kriteriene

7. oktober 2015

Sist bekreftet

1. oktober 2015

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 20060341

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Kliniske studier på AMG 386

Søk i lignende forsøk

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

CROs by country

CROs in Czech Republic

Forhold

Sjeldne sykdommer

Legemiddelintervensjoner

Kosttilskudd

Sponsor / samarbeidspartnere

Steder

Abonnere