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A Phase II Combination of Trastuzumab and Ixabepilone Versus Trastuzumab and Docetaxel in Patients With Advanced and/or Metastatic Breast Cancer

9 febbraio 2016 aggiornato da: R-Pharm

Randomized Phase II Study of Ixabepilone Plus Trastuzumab vs. Docetaxel Plus Trastuzumab in Female Subjects With Her2+ Locally Advanced and/or Metastatic Breast Cancer

The purpose of this randomized, Phase 2 open-label study was to assess the response rate of participants with Human Epidermal Growth Factor Receptor 2 (Her2+) locally advanced and/or metastatic breast cancer (not previously treated with chemotherapy or trastuzumab) to treatment with ixabepilone plus trastuzumab and/or docetaxel plus trastuzumab.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Effettivo)

50

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
      • Caen, Francia, F-14076
        • Local Institution
      • Grenoble, Francia, 38028
        • Local Institution
      • St Priest En Jarez, Francia, 42271
        • Local Institution
      • Toulouse, Francia, 31300
        • Local Institution
  • Grecia
      • Athens, Grecia, 11522
        • Local Institution
      • Athens, Grecia, 12462
        • Local Institution
      • Pireaus, Grecia, 18537
        • Local Institution
  • Italia
      • Bologna, Italia, 40138
        • Local Institution
      • Brescia, Italia, 25123
        • Local Institution
      • Modena, Italia, 41100
        • Local Institution
      • Napoli, Italia, 80131
        • Local Institution
      • Roma, Italia, 00144
        • Local Institution
      • Sora, Italia, 03039
        • Local Institution
  • Spagna
      • Madrid, Spagna, 28034
        • Local Institution
      • Madrid, Spagna, 28007
        • Local Institution
  • Tacchino
      • Ankara, Tacchino, 06100
        • Local Institution
      • Ankara, Tacchino, 06500
        • Local Institution
      • Izmir, Tacchino, 35100
        • Local Institution
      • Izmir, Tacchino, 35340
        • 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

Femmina

Descrizione

Inclusion Criteria:

  • Locally advanced or metastatic HER2+ breast cancer not previously treated with chemotherapy or trastuzumab.
  • Subjects who had received prior (neo)adjuvant chemotherapy or trastuzumab were eligible except if they relapsed within 12 months after the last dose of a taxane or trastuzumab given as (neo)adjuvant therapy.
  • Measurable disease
  • Left Ventricular Ejection Fraction (LVEF) ≥50%

Exclusion Criteria:

  • Prior chemotherapy or trastuzumab for metastatic breast cancer (MBC)
  • Relapse within 1 year after (neo)adjuvant taxane or trastuzumab
  • Neuropathy > Grade 1
  • Significant cardiovascular disease
  • Any brain metastases

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: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Arm A
trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
Droga: ixabepilone

Ixabepilone 40 mg/m^2 was administered as a 3-hour I.V. continuous infusion on Day 1 in a 21-day cycle until disease progression or unacceptable toxicity.

For the first cycle, ixabepilone was administered the day following the first dose of trastuzumab (in the first cycle trastuzumab was given on Day 0); in all the following cycles, ixabepilone was administered immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.

Altri nomi:
  • BMS-247550
  • Epotilone
  • IXEMPRA®
Droga: trastuzumab
Trastuzumab was administered as an IV infusion on Days 1, 8, and 15 of each 21-day cycle at a dose of 2 mg/kg until disease progression or unacceptable toxicity. In cycle 1, a loading dose of 4 mg/kg was administered as a 90-minute IV infusion on a day before initial administration of chemotherapy (i.e. on Day 0). Trastuzumab was given immediately prior to ixabepilone (Arm A) or docetaxel (Arm B) in all subsequent cycles as a 30-minute IV infusion if the initial dose was well tolerated.
Comparatore attivo: Arm B
trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
Droga: trastuzumab
Trastuzumab was administered as an IV infusion on Days 1, 8, and 15 of each 21-day cycle at a dose of 2 mg/kg until disease progression or unacceptable toxicity. In cycle 1, a loading dose of 4 mg/kg was administered as a 90-minute IV infusion on a day before initial administration of chemotherapy (i.e. on Day 0). Trastuzumab was given immediately prior to ixabepilone (Arm A) or docetaxel (Arm B) in all subsequent cycles as a 30-minute IV infusion if the initial dose was well tolerated.
Droga: docetaxel
Docetaxel 100 mg/m^2 was administered as a 1-hour IV continuous infusion on Day 1 in a 21-day cycle until disease progression or unacceptable toxicity. For the first cycle, docetaxel was administered the day following the first dose of trastuzumab (i.e. in the first cycle trastuzumab was given on Day 0); in all following cycles, docetaxel was administered immediately after trastuzumab if the preceding dose of trastuzumab was well tolerated.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Percentage of Participants With Objective Response (OR; Assessed by Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1)
Lasso di tempo: Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks)
Percentage of participants with best overall response (BOR) of either complete response (CR) or partial response (PR) according to RECIST version 1.1 as determined by the investigator. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. A two-sided confidence interval (CI) was computed using the Clopper-Pearson method.
Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks)
Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Lasso di tempo: Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks).
BOR was the best response recorded from the start of treatment until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the LD of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. Refer to Outcome Measure 3 for definition of PD.
Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks).

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Progression Free Survival (PFS)
Lasso di tempo: From randomization until the first date of documented progressive disease (PD) or death from any cause without prior documentation of progression (maximum participant PFS of 39.7 months).

Time in months from randomization until first date of documented progressive disease (PD) or death from any cause without prior documentation of progression. PD=≥20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall.

Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by the Brookmeyer and Crowley method.
From randomization until the first date of documented progressive disease (PD) or death from any cause without prior documentation of progression (maximum participant PFS of 39.7 months).
Time to Response
Lasso di tempo: From randomization every 6 weeks for first 12 months and thereafter every 3 months until CR or PR whichever was recorded first (maximum participant time to response of 18.4 weeks.)

Time to response was defined as the time in weeks from randomization until the measurement criteria are first met for a CR or PR, whichever is recorded first.

CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the LD of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by the Brookmeyer and Crowley method.
From randomization every 6 weeks for first 12 months and thereafter every 3 months until CR or PR whichever was recorded first (maximum participant time to response of 18.4 weeks.)
Duration of Response
Lasso di tempo: From the date of first PR or CR assessment to the date of documented progressive disease or death without prior documentation of progression (maximum participant duration of response of 38 months.)

Period measured in months from time that measurement criteria were first met for CR or PR until first date of documented PD or death from any cause without prior documentation of progression.

PD=≥20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall. Refer to Outcome Measure 1 for definitions of CR and PR. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by Brookmeyer and Crowley method.
From the date of first PR or CR assessment to the date of documented progressive disease or death without prior documentation of progression (maximum participant duration of response of 38 months.)
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0
Lasso di tempo: Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
AE: New untoward medical occurrence or worsening of a preexisting medical condition that does not have causal relationship with this treatment. SAE: Untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency/abuse; life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization/prolongs existing hospitalization. Grade 3=Severe; and Grade 4=Life-threatening or disabling. GR=Grade.
Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0
Lasso di tempo: Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)
Grade (GR)1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. White blood cell (WBC):GR1=<LLN-3.0*10^9/L; GR2=<3.0-2.0*10^9/L; GR3=<2.0-1.0*10^9/L; GR4=<1.0*10^9/L. Absolute Neutrophil Count (ANC):GR1=<LLN-1.5*10^9 /L; GR2=<1.5-1.0*10^9/L; GR3=<1.0-0.5*10^9/L; GR4=<0.5*10^9/L. Platelets:GR1=<LLN-75.0*10^9/L; GR2=<75.0-50.0*10^9/L; GR3=<50.0-25.0*10^9/L, GR4=<25.0*10^9/L. Hemoglobin:GR1=<LLN-10.0g/dL; GR2=<10.0-8.0g/dL; GR3=<8.0-6.5g/dL, GR4=<6.5g/dL. LLN=lower limit of normal.
Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0
Lasso di tempo: Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)
Grading: NCI CTCAE, Version 3.0. GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST): GR1=>ULN-2.5*ULN; GR2=>2.5-5.0*ULN; GR3=>5.0-20.0*ULN; GR4=>20.0*ULN. Total bilirubin: GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3-10*ULN, GR4=>10*ULN. Creatinine: GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3.0-6.0*ULN, GR4=>6.0*ULN. ULN=upper limit of normal.
Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)

Collaboratori e investigatori

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

Sponsor

R-Pharm

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 2008

Completamento primario (Effettivo)

1 giugno 2011

Completamento dello studio (Effettivo)

1 novembre 2011

Date di iscrizione allo studio

Primo inviato

21 giugno 2007

Primo inviato che soddisfa i criteri di controllo qualità

22 giugno 2007

Primo Inserito (Stima)

25 giugno 2007

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

10 marzo 2016

Ultimo aggiornamento inviato che soddisfa i criteri QC

9 febbraio 2016

Ultimo verificato

1 febbraio 2016

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • CA163-140
  • Eudract No: 2007-000721-21

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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