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Study of Dasatinib (BMS-354825) in Patients With Advanced Estrogen/Progesterone Receptor-positive (ER+/PR+) or Her2/Neu-positive (Her2/Neu+)Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00371345
Recruitment Status : Completed
First Posted : September 4, 2006
Results First Posted : November 5, 2010
Last Update Posted : April 26, 2011
Sponsor:
Information provided by:
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE September 1, 2006
First Posted Date  ICMJE September 4, 2006
Results First Submitted Date  ICMJE October 6, 2010
Results First Posted Date  ICMJE November 5, 2010
Last Update Posted Date April 26, 2011
Study Start Date  ICMJE December 2006
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 7, 2010)
  • Number of Participants With Objective Response [ Time Frame: From day of first treatment through Week 25 or at time of discontinuation from study treatment. ]
    Tumor response was assessed according RECIST criteria: PR=at least 30% reduction in the sum of the LD of all target lesions in reference to the baseline sum LD, CR=Disappearance of all non-target lesions. Objective tumor response was defined as a PR or CR.
  • Percentage of Participants With Objective Response [ Time Frame: From day of first treatment through Week 25 or at time of discontinuation from study treatment ]
    Tumor response was assessed according RECIST criteria: PR=at least 30% reduction in the sum of the LD of all target lesions in reference to the baseline sum LD, CR=Disappearance of all non-target lesions. Percentage of participants with objective tumor response was determined by the number of participants with PR or CR divided by the total number of response-evaluable participants.
  • Best Overall Response [ Time Frame: From day of first treatment through Week 25 or at time of discontinuation from study treatment ]
    Response assessed using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR)=disappearance of all target and non-target lesions; Partial Response (PR)=≥30% decrease in sum of longest diameter (LD) of target lesions; SD=small changes not meeting above criteria; Progressive Disease (PD)=appearance of new lesion(s), ≥ 20% increase in the sum of the LD of target lesions, or progression of existing non-target lesions; Clinical Progression (cPD)=deterioration related to disease requiring treatment without radiographic PD.
Original Primary Outcome Measures  ICMJE
 (submitted: September 1, 2006)
To estimate the objective response rate (ORR) of dasatinib in women with locally-advanced or metastatic breast cancer.
Change History Complete list of historical versions of study NCT00371345 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2010)
  • Number of Response-evaluable Participants With Disease Control (DCR) [ Time Frame: From day of first treatment through Week 25 or at time of discontinuation from study treatment. ]
    Disease control was defined in response-evaluable participants as having a best response of CR or PR (or uPR), or SD at/after 16 Weeks.
  • Percentage of Response-evaluable Participants With Disease Control (DCR) [ Time Frame: From day of first treatment through Week 25 or at time of discontinuation from study treatment. ]
    Disease control was defined in response-evaluable participants as having a best response of objective response (CR or PR) or SD at/after 16 Weeks.
  • Number of Participants Who Progressed [ Time Frame: From Baseline (Week 0) to time of PD or discontinuation of last participant from study treatment (Week 45) ]
    PFS was defined as time from first dosing date until the first date that Progressive Disease (PD) was observed.
  • Median Progression Free Survival (PFS) [ Time Frame: From Baseline (Week 0) to time of PD or discontinuation of last participant from study treatment (Week 45) ]
    PFS was defined as time from first dosing date until the first date that PD was observed. The distribution of PFS was estimated using the Kaplan-Meier product limit method. A two-sided 95% confidence interval (Brookmeyer and Crowley method) for the median PFS was computed.
  • Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25 [ Time Frame: At Weeks 9, 17, and 25 ]
    PFS was defined as time from first dosing date until the first date that progressive disease (PD) was observed.
  • Duration Of Objective Response [ Time Frame: the time (in weeks) between the first date that criteria for PR were met and the first date that PD or cPD was observed ]
    Duration of objective response was defined as the time (in weeks) between the first date that criteria for CR or PR were met and the first date that progressive disease (PD) or clinical progressive disease (cPD) was observed. Date of death was used as PD date for participants who died before reporting PD. Participants who neither progressed nor died were censored at the date of their last tumor assessment.
  • Number of Participants With Death, Adverse Events (AEs), and AEs Leading to Discontinuation [ Time Frame: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug ]
    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.
  • Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities [ Time Frame: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug ]
    Normal ranges for laboratory abnormalities: granulocytes=1.5x10^3-8x10^3 mm^3 (range may have varied by institution); hemoglobin=12-16 g/dL; platelets=150-440x10^9c/L; partial thromboplastin time=27-37.1 seconds; alkaline phosphatase=38-126 U/L; alanine aminotransferase=15-48 U/L; aspartate aminotransferase=14-38 U/L; creatine=0.7-1.1 mg/dL; hypokalemia (potassium [K])=3.5-5mEq/L; hyponatremia (sodium [Na])=135-145 mEq/L; phosphorous=2.4-4.5 mg/dL; bilirubin=0-1.2. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening/disabling, Gr 5=Death.
  • Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs [ Time Frame: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug ]
    AEs and SAEs considered possibly, probably, or certainly related to study treatment, graded according to CTCAE Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death). SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
  • Number Of Participants With Notable Drug-related AEs [ Time Frame: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug ]
    Notable drug-related AEs for dasatinib include gastrointestinal symptoms (diarrhea, nausea, vomiting and abdominal pain), fatigue, lethargy, headache, rash, fever, pleural effusion, and dyspnea.
  • Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3 [ Time Frame: PK assessment was performed at Week 3 visit (Day 15 ±4 days). Blood samples were obtained at Time = 0 hours, and at 1, 3 and 6 hours after each dose, and a trough sample was obtained immediately prior to any dose (~12 hours). ]
    Blood samples (3 mL) were used for measurement of dasatinib plasma concentration and metabolites.
  • PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 [ Time Frame: PK assessment was performed at Week 7 or 9 visit. Blood samples were obtained at Time = 0 hours, and at 1, 3 and 6 hours after each dose, and a trough sample was obtained immediately prior to any dose (~12 hours). ]
    Blood samples (3 mL) were used for measurement of dasatinib plasma concentration and metabolites.
  • Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 3 in Participants With and Without DCR [ Time Frame: At Baseline and Week 3 of treatment (Day 15 ±4 days) ]
    Collagen Type IV is a circulating marker related to the modulation of the vascular endothelial growth factor (VEGF)-pathway. An assay of Collagen Type IV in plasma was performed by ELISA.
  • Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 5 in Participants With and Without DCR [ Time Frame: Week 5 ]
    Collagen Type IV is a circulating marker related to the modulation of the vascular endothelial growth factor (VEGF)-pathway. An assay of Collagen Type IV in plasma was performed by ELISA.
  • Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 3 in Participants With and Without DCR [ Time Frame: At Baseline and Week 3 of treatment (Day 15 ±4 days) ]
    VEGF-stimulated disruption of the cadherin-catenin complex leads to tumor cell invasion and metastasis. VEGFR2 plasma levels were assayed by ELISA as a marker of VEGF pathway modulation.
  • Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 5 in Participants With and Without DCR [ Time Frame: At Baseline and Week 5 of treatment ]
    VEGF-stimulated disruption of the cadherin-catenin complex leads to tumor cell invasion and metastasis. VEGFR2 plasma levels were assayed by ELISA as a marker of VEGF pathway modulation.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2006)
  • Estimate disease control rate (DCR) and proportion of free or progression-free survival (PFS) distribution, and response duration
  • Determine the safety and tolerability of dasatinib in this patient population
  • Obtain PK and PD data during treatment
  • Obtain preliminary pharmacogenomics data
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Dasatinib (BMS-354825) in Patients With Advanced Estrogen/Progesterone Receptor-positive (ER+/PR+) or Her2/Neu-positive (Her2/Neu+)Breast Cancer
Official Title  ICMJE Phase II Study of Dasatinib (BMS-354825) for Advanced Estrogen/Progesterone Receptor-Positive or Her2/Neu-Positive Breast Cancer
Brief Summary This study will determine whether the investigational drug dasatinib is effective in treatment of women with progressive advanced ER+/PR+ or Her2/neu+ breast cancer
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Metastasis
Intervention  ICMJE
  • Drug: Dasatinib
    Tablets, Oral, 70 mg, twice daily, as long as the participant benefits (average <6 months)
    Other Names:
    • Sprycel
    • BMS-354825
  • Drug: Dasatinib 100 mg
    Tablets, Oral, 100mg, twice daily, as long as the participant benefits (average <6 months)
    Other Names:
    • Sprycel
    • BMS-354825
Study Arms  ICMJE Experimental: Dasatinib
Participants with either a Human epidermal growth factor (Her2/neu)-amplified tumor type or ER and/or PgR positive tumor types received oral dasatinib twice daily (BID).
Interventions:
  • Drug: Dasatinib
  • Drug: Dasatinib 100 mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 7, 2010)
92
Original Enrollment  ICMJE
 (submitted: September 1, 2006)
90
Actual Study Completion Date  ICMJE May 2009
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • females, 18 or older
  • recurrent, locally advanced, or metastatic breast cancer with expression of ER/PR receptor and/or overexpression of Her2/neu
  • paraffin-embedded tissue block must be available
  • measurable disease
  • prior chemotherapy with an anthracycline and/or a taxane (neoadjuvant, adjuvant, or metastatic setting)
  • 0, 1 or 2 chemotherapies in the metastatic setting
  • adequate organ function

Exclusion Criteria:

  • Metastatic disease confined to bone only
  • Symptomatic central nervous system (CNS) metastasis
  • Concurrent medical condition which may increase the risk of toxicity
  • Unable to take oral medication
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Belgium,   France,   Italy,   Peru,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00371345
Other Study ID Numbers  ICMJE CA180-088
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Study Director, Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date April 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP