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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 ottobre 2015 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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 di studio

Interventistico

Iscrizione (Effettivo)

228

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • 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
  • Belgio
      • Leuven, Belgio, 3000
        • Research Site
      • Liege, Belgio, 4000
        • Research Site
      • Wilrijk, Belgio, 2610
        • Research Site
  • Danimarca
      • Herlev, Danimarca, 2730
        • 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
  • 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
  • Olanda
      • Maastricht, Olanda, 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
  • Regno Unito
      • Guildford, Regno Unito, GU2 7XX
        • Research Site
      • Leicester, Regno Unito, LE1 5WW
        • Research Site
      • London, Regno Unito, W6 8RF
        • Research Site
      • London, Regno Unito, NW1 2PG
        • Research Site
      • Manchester, Regno Unito, M20 4BX
        • Research Site
      • Northwood, Regno Unito, HA6 2RN
        • Research Site
      • Nottingham, Regno Unito, NG5 1PB
        • Research Site
  • Spagna
      • Madrid, Spagna, 28033
        • Research Site
    • AndalucÃ-a
      • Jaén, AndalucÃ-a, Spagna, 23007
        • Research Site
    • Cataluña
      • Sabadell, Cataluña, Spagna, 08208
        • Research Site
    • Galicia
      • Santiago de Compostela, Galicia, Spagna, 15706
        • Research Site
  • Stati Uniti
    • Arizona
      • Litchfield Park, Arizona, Stati Uniti, 85340
        • Research Site
      • Tucson, Arizona, Stati Uniti, 85724
        • Research Site
    • Arkansas
      • Hot Springs, Arkansas, Stati Uniti, 71913
        • Research Site
      • Little Rock, Arkansas, Stati Uniti, 72205
        • Research Site
    • California
      • Campbell, California, Stati Uniti, 95008
        • Research Site
      • Los Angeles, California, Stati Uniti, 90095
        • Research Site
      • Murrieta, California, Stati Uniti, 92562
        • Research Site
      • Santa Maria, California, Stati Uniti, 93454
        • Research Site
    • Connecticut
      • New Haven, Connecticut, Stati Uniti, 06520
        • Research Site
      • Stamford, Connecticut, Stati Uniti, 06902
        • Research Site
    • Florida
      • Orlando, Florida, Stati Uniti, 32804
        • Research Site
    • Minnesota
      • Robbinsdale, Minnesota, Stati Uniti, 55422
        • Research Site
    • Nevada
      • Henderson, Nevada, Stati Uniti, 89052
        • Research Site
    • New Hampshire
      • Lebanon, New Hampshire, Stati Uniti, 03756
        • Research Site
      • Nashua, New Hampshire, Stati Uniti, 03061
        • Research Site
    • New Jersey
      • Edison, New Jersey, Stati Uniti, 08820
        • Research Site
      • Mountain Lakes, New Jersey, Stati Uniti, 07046
        • Research Site
    • North Carolina
      • Asheville, North Carolina, Stati Uniti, 28806
        • Research Site
      • Charlotte, North Carolina, Stati Uniti, 28203
        • Research Site
    • Pennsylvania
      • Hershey, Pennsylvania, Stati Uniti, 17033
        • Research Site
      • Philadelphia, Pennsylvania, Stati Uniti, 19106
        • Research Site
    • South Carolina
      • Columbia, South Carolina, Stati Uniti, 29210
        • Research Site
    • Texas
      • Richardson, Texas, Stati Uniti, 75080
        • Research Site
      • San Antonio, Texas, Stati Uniti, 78229
        • Research Site
      • Sugar Land, Texas, Stati Uniti, 77479
        • Research Site
    • Utah
      • Ogden, Utah, Stati Uniti, 84403
        • Research Site
  • Ungheria
      • Gyula, Ungheria, 5700
        • Research Site
      • Kaposvar, Ungheria, 7400
        • Research Site
      • Szombathely, Ungheria, 9700
        • Research Site
      • Veszprem, Ungheria, 8200
        • Research Site

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

Sì

Sessi ammissibili allo studio

Femmina

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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)
Sperimentale: 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)
Sperimentale: 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)
Comparatore attivo: 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]

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Lasso di tempo
Progression-free survival (PFS)
Lasso di tempo: 3 YEARS
3 YEARS

Misure di risultato secondarie

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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Amgen

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Collegamenti utili

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 luglio 2007

Completamento primario (Effettivo)

1 agosto 2010

Completamento dello studio (Effettivo)

1 maggio 2014

Date di iscrizione allo studio

Primo inviato

2 agosto 2007

Primo inviato che soddisfa i criteri di controllo qualità

2 agosto 2007

Primo Inserito (Stima)

3 agosto 2007

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

29 ottobre 2015

Ultimo aggiornamento inviato che soddisfa i criteri QC

7 ottobre 2015

Ultimo verificato

1 ottobre 2015

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 20060341

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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