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

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00371345
First received: September 1, 2006
Last updated: April 21, 2011
Last verified: April 2011
  Purpose

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


Condition Intervention Phase
Breast Cancer
Metastasis
Drug: Dasatinib
Drug: Dasatinib 100 mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Dasatinib (BMS-354825) for Advanced Estrogen/Progesterone Receptor-Positive or Her2/Neu-Positive Breast Cancer

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With Objective Response [ Time Frame: From day of first treatment through Week 25 or at time of discontinuation from study treatment. ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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). ] [ Designated as safety issue: No ]
    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). ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 92
Study Start Date: December 2006
Study Completion Date: May 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00371345

Locations
United States, California
Ucsf-Comprehensive Cancer Center
San Francisco, California, United States, 94143
United States, Florida
Mayo Clinic Florida
Jacksonville, Florida, United States, 32224
United States, Massachusetts
Dana-Farber Cancer Inst
Boston, Massachusetts, United States, 02115
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10461
United States, North Carolina
University Of North Carolina At Chapel Hill
Chapel Hill, North Carolina, United States, 275997305
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
University Of Texas Md Anderson Cancer Ctr
Houston, Texas, United States, 77030
Argentina
Local Institution
Haedo, Buenos Aires, Argentina, 1684
Local Institution
Buenos Aires, Argentina, 1185
Local Institution
Buenos Aires, Argentina, 1019
Belgium
Local Institution
Bruxelles, Belgium, 1000
Local Institution
Bruxelles, Belgium, 1200
France
Local Institution
Dijon Cedex, France, 21079
Local Institution
Paris, France, 75231
Local Institution
Saint Herblain Cedex, France, 44805
Local Institution
Toulouse Cedex 3, France, 31052
Italy
Local Institution
Modena, Italy, 41100
Peru
Local Institution
Arequipa, Peru
Local Institution
Lima, Peru, 34
Local Institution
Lima, Peru, LIMA 11
Spain
Local Institution
Barcelona, Spain, 08035
Local Institution
Lleida, Spain, 25198
Local Institution
Madrid, Spain, 28041
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00371345     History of Changes
Other Study ID Numbers: CA180-088
Study First Received: September 1, 2006
Results First Received: October 6, 2010
Last Updated: April 21, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Bristol-Myers Squibb:
Recurrent, locally-advanced, or metastatic breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Estrogens
Progesterone
Dasatinib
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Progestins
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014