A Phase II Combination of Trastuzumab and Ixabepilone Versus Trastuzumab and Docetaxel in Patients With Advanced and/or Metastatic Breast Cancer
9. února 2016 aktualizováno: 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.
Přehled studie
Postavení
Dokončeno
Podmínky
Intervence / Léčba
Typ studie
Intervenční
Zápis (Aktuální)
50
Fáze
- Fáze 2
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Caen, Francie, F-14076
- Local Institution
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Grenoble, Francie, 38028
- Local Institution
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St Priest En Jarez, Francie, 42271
- Local Institution
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Toulouse, Francie, 31300
- Local Institution
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Bologna, Itálie, 40138
- Local Institution
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Brescia, Itálie, 25123
- Local Institution
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Modena, Itálie, 41100
- Local Institution
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Napoli, Itálie, 80131
- Local Institution
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Roma, Itálie, 00144
- Local Institution
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Sora, Itálie, 03039
- Local Institution
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Ankara, Krocan, 06100
- Local Institution
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Ankara, Krocan, 06500
- Local Institution
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Izmir, Krocan, 35100
- Local Institution
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Izmir, Krocan, 35340
- Local Institution
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Athens, Řecko, 11522
- Local Institution
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Athens, Řecko, 12462
- Local Institution
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Pireaus, Řecko, 18537
- Local Institution
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Madrid, Španělsko, 28034
- Local Institution
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Madrid, Španělsko, 28007
- Local Institution
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let a starší (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Ženský
Popis
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
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: 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.
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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.
Ostatní jména:
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.
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Aktivní komparátor: 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.
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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.
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.
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Percentage of Participants With Objective Response (OR; Assessed by Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1)
Časové okno: 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)
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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.
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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)
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Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Časové okno: 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).
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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.
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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).
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Progression Free Survival (PFS)
Časové okno: 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).
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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).
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Time to Response
Časové okno: 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.)
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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.)
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Duration of Response
Časové okno: 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.)
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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.)
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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
Časové okno: 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.)
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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.
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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.)
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Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0
Časové okno: 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.)
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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.
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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.)
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Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0
Časové okno: 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.)
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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.
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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.)
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
1. února 2008
Primární dokončení (Aktuální)
1. června 2011
Dokončení studie (Aktuální)
1. listopadu 2011
Termíny zápisu do studia
První předloženo
21. června 2007
První předloženo, které splnilo kritéria kontroly kvality
22. června 2007
První zveřejněno (Odhad)
25. června 2007
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
10. března 2016
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
9. února 2016
Naposledy ověřeno
1. února 2016
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- CA163-140
- Eudract No: 2007-000721-21
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .