Safety and Efficacy of Exemestane Plus Dasatinib Versus Placebo for Advanced ER+ Breast Cancer
22. února 2013 aktualizováno: 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).
Přehled studie
Postavení
Postavení
Dokončeno
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Typ studie
Typ studie
Intervenční
Zápis (Aktuální)
Zápis
155
Fáze
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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Lille, Francie, 59000
- Local Institution
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Paris Cedex 13, Francie, 75651
- Local Institution
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Saint-Cloud Cedex, Francie, 92211
- Local Institution
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Dublin, Irsko, 24
- Local Institution
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Gdansk, Polsko, 80-952
- Local Institution
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Gdansk, Polsko, 80-462
- Local Institution
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Lodz, Polsko, 93-509
- Local Institution
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Opole, Polsko, 45-060
- Local Institution
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Essex
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Chelmsford, Essex, Spojené království, CM1 7ET
- Local Institution
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Greater London
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London, Greater London, Spojené království, NW1 2BU
- Local Institution
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Warwickshire
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Coventry, Warwickshire, Spojené království, CV22DX
- Local Institution
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California
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Fountain Valley, California, Spojené státy, 92708
- Compassionate Cancer Care Medical Group, Inc
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Riverside, California, Spojené státy, 92501
- Compassionate Cancer Care Medical Group Inc
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Pennsylvania
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Philadelphia, Pennsylvania, Spojené státy, 19106
- Pennsylvania Oncology/Hematology Associates
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Tennessee
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Memphis, Tennessee, Spojené státy, 38120
- The West Clinic
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Hradec Kralove, Česká republika, 500 05
- Local Institution
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Prague 5, Česká republika, 150 06
- Local Institution
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Madrid, Španělsko, 28041
- Local Institution
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Madrid, Španělsko, 28033
- Local Institution
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Torrevieja, Španělsko, 03186
- Local Institution
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Vasteras, Švédsko, 72189
- 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
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let a starší (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
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
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: Dvojnásobek
Počet zbraní
2
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
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Aktivní komparátor: A
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Tablets, Oral, Exemestane 25 mg + Dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity
Ostatní jména:
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Komparátor placeba: B
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Tablets, Oral, Exemestane 25 mg + Placebo 100 mg, once daily, until disease progression or unacceptable toxicity
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Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Progression Free Survival (PFS) Distribution for Exemestane Plus Dasatinib vs Exemestane Plus Placebo
Časové okno: Prior to study therapy, at 8 week intervals until progression occurs (maximum participant PFS of 71 weeks)
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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).
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Prior to study therapy, at 8 week intervals until progression occurs (maximum participant PFS of 71 weeks)
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Participants With Disease Progression or Death for Exemestane Plus Dasatinib vs Exemestane Plus Placebo
Časové okno: Prior to study therapy, at 8 week intervals until progression occurs. Maximum participant PFS of ____ months)
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PD is an increase (≥ 20%) in sum of longest diameters from smallest value during study (including baseline).
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Prior to study therapy, at 8 week intervals until progression occurs. Maximum participant PFS of ____ months)
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Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Number of Participants With Best Overall Response
Časové okno: at 6 months
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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).
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at 6 months
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Percentage of Participants With Clinical Benefit (CB) for Exemestane Plus Dasatinib Arm vs Exemestane Plus Placebo Arm at 6 Months
Časové okno: at 6 months
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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.
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at 6 months
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Percentage of Participants With Response in Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms
Časové okno: Prior to study therapy, at 8 week intervals until progression occurs (maximum participant response was 39 weeks)
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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.
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Prior to study therapy, at 8 week intervals until progression occurs (maximum participant response was 39 weeks)
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Participants With Freedom-From-Progression (FFP) at 6 Months
Časové okno: at 6 months
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FFP at month 6 is defined for the randomized participants who had the probability of neither progressing nor dying before 6 months.
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at 6 months
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Time to Response for Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms
Časové okno: 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
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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.
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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
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Duration of Response for Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms
Časové okno: 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.
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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).
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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.
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Changes in Participant-reported Pain Intensity in Participants With Bone Metastasis
Časové okno: 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.
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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".
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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.
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Changes in Markers of Bone Lysis in Participants With Bone Metastasis
Časové okno: 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.
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Assay for urinary N-telopeptide was used to evaluate Osteolytic activity.
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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.
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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)
Časové okno: 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.
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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.
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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.
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Number of Participants With Grade 1-4 Hematology Abnormalities (as Per the NCI CTCAE, Version 3.0)
Časové okno: 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.
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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.
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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.
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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)
Časové okno: 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.
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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.
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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.
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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)
Časové okno: 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.
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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.
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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.
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Number of Participants With Abnormalities in Vital Signs
Časové okno: 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.
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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.
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Number of Participants With Abnormalities in Electrocardiograms
Časové okno: 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.
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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.
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Sponzor
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Užitečné odkazy
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
Začátek studia
1. února 2009
Primární dokončení (Aktuální)
Primární dokončení
1. března 2011
Dokončení studie (Aktuální)
Dokončení studie
1. prosince 2012
Termíny zápisu do studia
První předloženo
První předloženo
6. října 2008
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
6. října 2008
První zveřejněno (Odhad)
První zveřejněno
7. října 2008
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
Poslední zveřejněná aktualizace
28. února 2013
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
22. února 2013
Naposledy ověřeno
Naposledy ověřeno
1. července 2012
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Kožní choroby
- Novotvary
- Novotvary podle místa
- Nemoci prsu
- Novotvary prsu
- Fyziologické účinky léků
- Molekulární mechanismy farmakologického působení
- Inhibitory enzymů
- Antineoplastická činidla
- Hormony, hormonální náhražky a antagonisté hormonů
- Inhibitory proteinkinázy
- Antagonisté hormonů
- Inhibitory aromatázy
- Inhibitory syntézy steroidů
- Antagonisté estrogenu
- Exemestan
- Dasatinib
Další identifikační čísla studie
Další identifikační čísla studie
- CA180-261
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 .