Questa pagina è stata tradotta automaticamente e l'accuratezza della traduzione non è garantita. Si prega di fare riferimento al Versione inglese per un testo di partenza.

Safety and Efficacy of Exemestane Plus Dasatinib Versus Placebo for Advanced ER+ Breast Cancer

22 febbraio 2013 aggiornato da: Bristol-Myers Squibb

A Randomized, Double-Blind, Multi-Center Phase II Trial of Exemestane (Aromasin®) Plus Dasatinib Versus Exemestane Plus Placebo in Advanced Estrogen Receptor-Positive Breast Cancer After Disease Progression on a Non-Steroidal Aromatase Inhibitor (NSAI)

The purpose of this study is to determine whether exemestane plus dasatinib will be well-tolerated and will increase progression-free survival (PFS) in the treatment of advanced estrogen-receptor positive (ER+) breast cancer after disease progression (PD) on a non-steroidal aromatase inhibitor (NSAI).

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Effettivo)

155

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

  • Francia
      • Lille, Francia, 59000
        • Local Institution
      • Paris Cedex 13, Francia, 75651
        • Local Institution
      • Saint-Cloud Cedex, Francia, 92211
        • Local Institution
  • Irlanda
      • Dublin, Irlanda, 24
        • Local Institution
  • Polonia
      • Gdansk, Polonia, 80-952
        • Local Institution
      • Gdansk, Polonia, 80-462
        • Local Institution
      • Lodz, Polonia, 93-509
        • Local Institution
      • Opole, Polonia, 45-060
        • Local Institution
  • Regno Unito
    • Essex
      • Chelmsford, Essex, Regno Unito, CM1 7ET
        • Local Institution
    • Greater London
      • London, Greater London, Regno Unito, NW1 2BU
        • Local Institution
    • Warwickshire
      • Coventry, Warwickshire, Regno Unito, CV22DX
        • Local Institution
  • Repubblica Ceca
      • Hradec Kralove, Repubblica Ceca, 500 05
        • Local Institution
      • Prague 5, Repubblica Ceca, 150 06
        • Local Institution
  • Spagna
      • Madrid, Spagna, 28041
        • Local Institution
      • Madrid, Spagna, 28033
        • Local Institution
      • Torrevieja, Spagna, 03186
        • Local Institution
  • Stati Uniti
    • California
      • Fountain Valley, California, Stati Uniti, 92708
        • Compassionate Cancer Care Medical Group, Inc
      • Riverside, California, Stati Uniti, 92501
        • Compassionate Cancer Care Medical Group Inc
    • Pennsylvania
      • Philadelphia, Pennsylvania, Stati Uniti, 19106
        • Pennsylvania Oncology/Hematology Associates
    • Tennessee
      • Memphis, Tennessee, Stati Uniti, 38120
        • The West Clinic
  • Svezia
      • Vasteras, Svezia, 72189
        • Local Institution

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

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Histologically-documented invasive estrogen receptor positive breast cancer , with tumor tissue from prior surgery available for analysis
  • Prior therapy with a non-steroidal aromatase inhibitor
  • Recurrent or progressive advanced breast cancer (locally-advanced or metastatic)
  • Documented breast cancer with tumor ≤ 28 days prior to study entry
  • Women who are NOT of childbearing potential
  • Must be able to take oral medication
  • Performance Status 0 or 1

Exclusion Criteria:

  • Pleural or pericardial effusion or ascites (of any etiology; Grade ≥ 1) within 6 months prior to study entry
  • Any chemotherapy, immunotherapy < 6 months before study entry. Any targeted therapy (eg. lapatinib) < 6 months before study entry, unless given in combination with an NSAI
  • Any antitumor therapy, including radiotherapy or hormonal therapy, within 15 days prior to study entry
  • Prior exposure to exemestane, any Src-family kinase inhibitor including dasatinib, to agents intended to control osteolytic disease other than bisphosphonates, or to any investigational agent for breast cancer
  • Concurrent or previous malignant disease requiring chemotherapy or radiation treatment within the prior 3 years
  • Significant bleeding disorder, or ongoing or recent clinically-significant gastrointestinal bleeding
  • Any serious cardiac condition, including congestive heart failure or myocardial infarction within 6 months, uncontrolled angina, or Class III or IV heart disease as defined by the New York Heart Association, baseline ejection fraction ≤ 40%, diagnosed congenital long QT syndrome, clinically-significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes), QTc interval > 450 msec at baseline (Fridericia correction)
  • Hematologic abnormality Grade ≥ 2
  • Hypocalcemia of Grade ≥ 1
  • Any Chemistry abnormality of Grade ≥ 2 [except Grade 2 indirect bilirubin permitted if diagnosed Gilbert's disease]
  • Pregnant Women and Women of Childbearing Potential (WOCBP)
  • Extremely lactose intolerant, in the judgment of treating physician (100 mg dasatinib contains 135 mg lactose, posing a problem only if intolerance is severe)
  • Receiving any of the following concomitant medications: Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Subjects must discontinue drug use at least 7 days prior to starting dasatinib)
  • Potent inhibitors of CYP3A4 isoenzyme
  • Prisoners or subjects who are involuntarily incarcerated; or subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

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: Doppio

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: UN
Droga: Exemestane + Dasatinib
Tablets, Oral, Exemestane 25 mg + Dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity
Altri nomi:
  • BMS-354825
  • Sprycel
Comparatore placebo: B
Droga: Exemestane + Placebo
Tablets, Oral, Exemestane 25 mg + Placebo 100 mg, once daily, until disease progression or unacceptable toxicity

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Progression Free Survival (PFS) Distribution for Exemestane Plus Dasatinib vs Exemestane Plus Placebo
Lasso di tempo: Prior to study therapy, at 8 week intervals until progression occurs (maximum participant PFS of 71 weeks)
PFS= The time (weeks) from date of randomization to date of progressive disease(PD). PFS for each randomization arm was estimated using the Kaplan-Meier product-limit method. A point estimate and a 95% confidence interval (CI) for the median PFS was computed for each randomization arm using the Brookmeyer & Crowley method. PD=Increase (≥ 20%) in sum of longest diameters from smallest value during study (including baseline).
Prior to study therapy, at 8 week intervals until progression occurs (maximum participant PFS of 71 weeks)
Participants With Disease Progression or Death for Exemestane Plus Dasatinib vs Exemestane Plus Placebo
Lasso di tempo: Prior to study therapy, at 8 week intervals until progression occurs. Maximum participant PFS of ____ months)
PD is an increase (≥ 20%) in sum of longest diameters from smallest value during study (including baseline).
Prior to study therapy, at 8 week intervals until progression occurs. Maximum participant PFS of ____ months)

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of Participants With Best Overall Response
Lasso di tempo: at 6 months
Complete response (CR) = Disappearance of all measurable and non-measurable lesions, and no new lesions; Partial response (PR) = Decrease ≥30% from baseline in sum of longest diameters (LD) of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions. SD = Disease re-assessment not qualifying as CR, PR or PD(≥20% increase in sum of longest diameters from smallest value).
at 6 months
Percentage of Participants With Clinical Benefit (CB) for Exemestane Plus Dasatinib Arm vs Exemestane Plus Placebo Arm at 6 Months
Lasso di tempo: at 6 months
CB = participants whose best response is CR, PR, or stable disease(SD). CR = Disappearance of all measurable and non-measurable lesions, and no new lesions; PR = Decrease ≥30% from baseline in sum of longest diameters of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions. SD = Disease re-assessment not qualifying as CR, PR or PD(≥20% increase in sum of longest diameters from smallest value). Confidence interval computed by Clopper-Pearson method.
at 6 months
Percentage of Participants With Response in Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms
Lasso di tempo: Prior to study therapy, at 8 week intervals until progression occurs (maximum participant response was 39 weeks)
Response= Proportion of response-evaluable participants whose best response is CR or PR. Confidence intervals was computed using the Clopper-Pearson method. CR = Disappearance of all measurable and non-measurable lesions, and no new lesions; PR = Decrease ≥30% from baseline in sum of longest diameters of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions.
Prior to study therapy, at 8 week intervals until progression occurs (maximum participant response was 39 weeks)
Participants With Freedom-From-Progression (FFP) at 6 Months
Lasso di tempo: at 6 months
FFP at month 6 is defined for the randomized participants who had the probability of neither progressing nor dying before 6 months.
at 6 months
Time to Response for Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms
Lasso di tempo: Prior to study therapy, at 8 week intervals until CR or PR. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug, whichever is longer
Time to response is defined as time from first dose of study therapy until measurement criteria are first met for PR or CR (whichever is recorded first). CR = Disappearance of all measurable and non-measurable lesions, and no new lesions; PR = Decrease ≥30% from baseline in sum of longest diameters of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions.
Prior to study therapy, at 8 week intervals until CR or PR. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug, whichever is longer
Duration of Response for Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms
Lasso di tempo: Prior to study therapy, at 8 week intervals. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug, whichever is longer.
Duration of response is defined as the time from date that measurement criteria are first met for PR or CR until first date of documented PD or death. CR = Disappearance of all measurable and non-measurable lesions, and no new lesions; PR = Decrease ≥30% from baseline in sum of longest diameters of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions. PD=Increase (≥ 20%) in sum of longest diameters from smallest value during study (including baseline).
Prior to study therapy, at 8 week intervals. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug, whichever is longer.
Changes in Participant-reported Pain Intensity in Participants With Bone Metastasis
Lasso di tempo: Start of study, at treatment start, after 2, 4, and 8 weeks of therapy and every 8 weeks thereafter, at end-of-treatment. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug.
Pain intensity evaluated by administration of the Brief Pain Inventory - Short Form (BPI-sf). The BPI-sf is a psychometrically-validated instrument which measures both pain severity and functional interference caused by pain using an 11-point numerical rating scale. Severity of pain at its "worst", "least" and "on average" in the last 24 hours, and "right now" (ie, at the time the questionnaire is being filled out) is recorded using anchors of "no pain" = "0" and "pain as bad as you can imagine" = "10".
Start of study, at treatment start, after 2, 4, and 8 weeks of therapy and every 8 weeks thereafter, at end-of-treatment. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug.
Changes in Markers of Bone Lysis in Participants With Bone Metastasis
Lasso di tempo: Screening, Day 1, after week 2, 4, and week 8 and subsequently every 8 weeks, at end-of-treatment. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug.
Assay for urinary N-telopeptide was used to evaluate Osteolytic activity.
Screening, Day 1, after week 2, 4, and week 8 and subsequently every 8 weeks, at end-of-treatment. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug.
Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AEs (as Per National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 3.0)
Lasso di tempo: From start of study drug therapy up to 30 days after the last dose. Median duration of therapy (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.
AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded. Grade (GR)1 = mild, GR 2 = moderate, GR 3=severe, GR 4=life threatening, GR 5=death.
From start of study drug therapy up to 30 days after the last dose. Median duration of therapy (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.
Number of Participants With Grade 1-4 Hematology Abnormalities (as Per the NCI CTCAE, Version 3.0)
Lasso di tempo: Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.
Abnormalities were graded per NCI-CTC, Version 3.0 criteria. Grade (GR)1 = mild, GR 2 = moderate, GR 3 = severe, GR 4 = life threatening. Normal ranges are provided by the Local Laboratory and may vary according to sex and age. Granulocytes, GR 1;<LLN-1.5x 10^9/L, GR 2:<1.5-1.0x10^9/L, GR 3: <1.0 - 0.5x10^9/L, GR, 4: <0.5x10^9 /L; Hemoglobin, GR 1: <LLN-10.0 g/dL, GR 2: <10.0-8.0 g/dL, GR 3: <8.0-6.5 g/dL, GR, 4: <6.5g/dL; Platelets, GR 1: <LLN-75.0x10^9/L, GR 2: <75.0-50.0x10^9/L, GR 3: <50.0-25.0x10^9/L; Leukocytes, GR 1: <LLN-3.0x10^9/L, GR 2: <3.0-2.0x10^9/L, GR 4: <1.0x10^9/L.
Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.
Number of Participants With Grade 1-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Bilirubin, Calcium, Creatinine, and Albumin (as Per the NCI CTCAE, Version 3.0)
Lasso di tempo: Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.
Grade (GR) 1 = mild, GR 2 = moderate, GR 3 = severe, GR 4 = life threatening). Normal ranges are provided by the Local Laboratory and may vary according to sex and age. Alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, GR 1: >ULN-2.5 x ULN (upper limit of normal), GR 2: >2.5-5.0 x ULN, GR 3: 5.0-20.0 x ULN; Low calcium, GR 1: <LLN - 8.0 mg/dL, GR 2: <8.0-7.0 mg/dL, GR 4:<6.0 mg/dL; High calcium, GR 1:>ULN - 11.5 mg/dL; bilirubin, GR 1: >ULN-1.5 x ULN,GR 3: >3-10 x ULN; Creatinine, GR1:>ULN-1.5 x ULN, GR2: >1.5-3.0 x ULN; Albumin, GR1:<LLN-3 g/dL,GR2:<3-2 g/dL.
Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.
Number of Participants With Grade 1-4 Serum Chemistry Abnormalities in Potassium, Magnesium, Sodium, Phosphorous, Uric Acid, and Bicarbonate (as Per the NCI CTCAE, Version 3.0)
Lasso di tempo: Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.
Grade (GR)1= mild, GR2= moderate, GR3= severe, GR4= life threatening. Ranges are provided by the local laboratory and may vary according to sex and age. Phosphorous, GR1:<LLN 2.5 mg/dL, GR2:<2.5-2.0 mg/dL, GR3: 1.0-<2.0 mg/dL; Low sodium,GR1:<LLN 130mmol/L, GR3:120-<130 mmol/L; High Magnesium, GR1 >ULN 3.0 mg/dL,GR 3:<0.3 0.8mg/dL; Uric acid, GR1:>ULN 10 mg/dL, GR4:>10 mg/dL; Low potassium, GR1:<LLN 3.0mmol/L,GR3:<3.0 2.5mmol/L; High potassium, GR1:>ULN-5.5 mmol/L, GR2:>5.5-6.0 mmol/L; Bicarbonate, GR1:<LLN-16 mmol/L; GR2:<16 - 11 mmol/L; Hig sodium, GR1:>ULN-150 mmol/L,GR2:>150-155 mmol/L.
Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.
Number of Participants With Abnormalities in Vital Signs
Lasso di tempo: Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment.
Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment.
Number of Participants With Abnormalities in Electrocardiograms
Lasso di tempo: Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment.
Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment.

Collaboratori e investigatori

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

Sponsor

Bristol-Myers Squibb

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.

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 febbraio 2009

Completamento primario (Effettivo)

1 marzo 2011

Completamento dello studio (Effettivo)

1 dicembre 2012

Date di iscrizione allo studio

Primo inviato

6 ottobre 2008

Primo inviato che soddisfa i criteri di controllo qualità

6 ottobre 2008

Primo Inserito (Stima)

7 ottobre 2008

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

28 febbraio 2013

Ultimo aggiornamento inviato che soddisfa i criteri QC

22 febbraio 2013

Ultimo verificato

1 luglio 2012

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • CA180-261

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 .

Prove cliniche su Cancro al seno

Prove cliniche su Exemestane + Dasatinib

Cerca prove simili

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

CROs by country

CROs in Venezuela

Condizioni

Malattie rare

Interventi farmacologici

Supplementi dietetici

Sponsor / Collaboratori

Sedi

Sottoscrivi