A Study of Dasatinib (BMS-354825) in Patients With Advanced 'Triple-negative' Breast Cancer

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00371254
First received: September 1, 2006
Last updated: February 18, 2011
Last verified: February 2011
  Purpose

This study will determine whether the investigational drug dasatinib is effective in treatment of women with progressive advanced triple-negative breast cancer.


Condition Intervention Phase
Breast Cancer
Metastasis
Drug: Dasatinib
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 'Triple-negative' Breast Cancer

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline to end of study drug therapy (up to 65 weeks). ] [ Designated as safety issue: No ]
    Tumor response was defined as the number of participants whose best response was CR or PR, per the Response Evaluation Criteria in Solid Tumor (RECIST): CR: disappearance of all target/non-target lesions; PR: >= 30% decrease in the sum of the LDs of target lesions relative to the baseline sum LD.

  • Percentage of Participants With Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline to end of study drug therapy (up to 65 weeks). ] [ Designated as safety issue: No ]
    The percentage of participants whose best response was CR or PR, per the RECIST: CR: disappearance of all target/non-target lesions; PR: >= 30% decrease in the sum of the LDs of target lesions relative to the baseline sum LD.


Secondary Outcome Measures:
  • Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study [ Time Frame: Baseline to 16 weeks. ] [ Designated as safety issue: No ]
    The number of participants whose best response was CR, PR or SD (per the RECIST) at or after 16 weeks on study: CR: disappearance of all target/non-target lesions; PR: >=30% decrease in the sum of the LDs of target lesions relative to baseline sum LD; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PD: appearance of new lesion/s, or >=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.

  • Percentage of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study [ Time Frame: Baseline to 16 weeks ] [ Designated as safety issue: No ]
    The percentage of participants whose best response was CR, PR or SD (per the RECIST) at or after 16 weeks on study: CR: disappearance of all target/non-target lesions; PR: >=30% decrease in the sum of the LDs of target lesions relative to baseline sum LD; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PD: appearance of new lesion/s, or >=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.

  • Proportion of Participants With Progression-Free Survival (PFS) at Weeks 9, 17, and 25 [ Time Frame: Weeks 9, 17, and 25 ] [ Designated as safety issue: No ]
    PFS:time from first dose until the date that progressive disease (PD) or clinical PD (cPD) observed,per RECIST criteria.PD:appearance of new lesion/s,or >=20% increase in the sum of the LD of target lesions,relative to smallest sum LD recorded since treatment start,or unequivocal progression of existing non-target lesions;cPD:deterioration related to disease requiring treatment discontinuation,but without radiographic PD.Participants who died without PD were considered to have PD on the date of death.For participants who neither progressed nor died,date of the last tumor assessment was used.

  • Mean Number of Weeks of Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline to end of study drug therapy (up to 53.86 weeks) ] [ Designated as safety issue: No ]
    Mean number of weeks of CR/PR (time from first date of CR/PR until first date PD observed. Tumor response defined per RECIST: CR: disappearance of all target/non-target lesions; PR: >=30% decrease in sum of LDs of target lesions relative to baseline sum LD; PD: appearance of new lesion or >=20% increase in sum of LD of target lesions relative to smallest sum LD or unequivocal progression of existing non-target lesions. Participants who died without reported PD were considered to have PD on date of death. For participants who neither progressed nor died, date of last tumor assessment used.

  • Mean Plasma Concentration at Week 3 [ Time Frame: At pre-dose and 1, 3, 6 and 12 hours after each dose administration ] [ Designated as safety issue: No ]
    Mean plasma concentration was obtained directly from the concentration-time data.

  • Mean Plasma Concentration at Week 7 [ Time Frame: At pre-dose and 1, 3, 6 and 12 hours after each dose administration ] [ Designated as safety issue: No ]
    Mean plasma concentration was obtained directly from the concentration-time data.

  • Mean Change in Concentration of Collagen Type IV From Baseline [ Time Frame: Baseline, Week 3 and Week 5 ] [ Designated as safety issue: No ]
    Collagen Type IV is a measure of anti-angiogenic activity. Plasma samples for assessment of change in concentration of Collagen Type IV were obtained and analyzed by enzyme-linked immunosorbent assay.

  • Mean Change in Concentration of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) From Baseline [ Time Frame: Baseline, Week 3 and Week 5 ] [ Designated as safety issue: No ]
    VEGFR2 is a measure of anti-angiogenic activity. Plasma samples for assessment of change in concentration of VEGFR2 were obtained and analyzed by enzyme-linked immunosorbent assay.

  • Percentage Change in Tumor Biomarkers [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Tumor markers are indicators of tumor activity which may be used to predict clinical benefit and circulating biomarkers may reveal key mechanisms of action. Tissue staining was performed for caveolin, phospho-caveolin, EphA2 and insulin-like growth factor binding protein 2 (IGFBP2) markers using immunohistochemistry assays.

  • Profiling of Messenger-ribonucleic Acid (mRNA) Expression: mRNA Signal Intensity [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Pharmacogenomic analysis included the assessment of the relationship between clinical benefit and mRNA expression levels and between clinical benefit and protein phosphorylation. Tumor mRNA expression was analyzed in all available tissues. mRNA was extracted from 96 formalin-fixed paraffin-embedded tissue (FFPET) samples, amplified, and fluorescently labeled. Gene expression profiling was conducted using Affymetrix Human Genome U133A 2.0 DNA microarrays. mRNA expression is reported as quantile normalized RMA values.

  • Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs) or Adverse Events (AEs) [ Time Frame: From start of study drug therapy up to 30 days after the last dose. ] [ Designated as safety issue: Yes ]
    An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). An SAE was defined as an AE that resulted in death, was life-threatening, required hospitalization (or prolongation of existing hospitalization), or was an important medical event.

  • Number of Participants Who Experienced Drug-related SAEs, Drug-related AEs, Drug-related Grade 3 AEs and Discontinuations Due to Drug-related AEs [ Time Frame: From start of study drug therapy up to 30 days after the last dose. ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence/worsening of pre-existing medical condition.SAE=AE that resulted in death, was life-threatening, required hospitalization (or prolongation of existing hospitalization), or was an important medical event. Drug-related SAEs or AEs are those events with relationship to study therapy of certain, probable or possible.AEs were graded using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), v3: Grade 1=mild, 2=moderate, 3=severe, 4=life threatening, 5=death.Participants who discontinued the study due to any drug-related AEs were also recorded.

  • Most Frequent Drug-related Adverse Events (AEs) [ Time Frame: From start of study drug therapy up to 30 days after the last dose. ] [ Designated as safety issue: Yes ]
    Most frequent drug-related AEs are those AEs with frequency >=25% in either group. Drug-related AEs are those events with relationship to study therapy of certain, probable or possible.

  • Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements [ Time Frame: Throughout study, from start of study drug therapy up to 30 days after the last dose. ] [ Designated as safety issue: Yes ]
    Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening. Grades 3 and 4 criteria are defined as follows: Granulocytes: Grade 3 <1.0 - 0.5 x 10^9/L; Grade 4, <0.5 x 10^9/L. Hemoglobin: Grade 3, <8.0 - 6.5 g/dL; Grade 4, <6.5 g/dL. Platelets: Grade 3, <50.0 - 25.0 x 10^9/L; Grade 4, <25.0 x 10^9/L. Leukocytes: Grade 3, <2.0 - 1.0 x 10^9/L; Grade 4, <1.0 x 10^9/L.

  • Number of Participants With Abnormalities (Grade 1 or 2) in Prothrombin Time (PT) [ Time Frame: Throughout study, from start of study drug therapy up to 30 days after the last dose. ] [ Designated as safety issue: Yes ]
    PT is a measure of the clotting ability of the blood. Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening and 5=death.

  • Number of Participants With Abnormalities (Grade 1 or 2) in Partial Thromboplastin Time (PTT) [ Time Frame: Throughout study, from start of study drug therapy up to 30 days after the last dose. ] [ Designated as safety issue: Yes ]
    PTT is a measure of the clotting ability of the blood. Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening and 5=death.

  • Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase [ Time Frame: Throughout study, from start of study drug therapy up to 30 days after the last dose. ] [ Designated as safety issue: Yes ]
    Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening. Grade 3 and 4 criteria are defined as follows: ALT, AST and alkaline phosphatase: Grade 3: >5-20 x upper limit of normal (ULN), Grade 4: >20 x ULN.

  • Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium [ Time Frame: Throughout study, from start of study drug therapy up to 30 days after the last dose. ] [ Designated as safety issue: Yes ]
    Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening. Grade 3 and 4 criteria are defined as follows: Calcium: Grade 3-4 : <6.0 - <7.0 or >12.5 - >13.5 mg/dL, Potassium: Grade 3-4 : <2.5 - <3.0 or >6.0 - >7.0 mEq/L, Magnesium: Grade 3-4 : <0.6 - <0.8 or >2.46 - >6.6 mEq/L, Sodium:< 120- 130 or >155 - >160 mEq/L.

  • Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total). [ Time Frame: Throughout study, from start of study drug therapy up to 30 days after the last dose. ] [ Designated as safety issue: Yes ]
    Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening. Grade 3 and 4 criteria are defined as follows: Creatinine: Grade 3-4 : > 3.0 -6.0 ULN (upper limit of normal),Bicarbonate: Grade 3-4: <16 -<22 mEq/L, Phosphorous: Grade 3-4 : <1.0 - <2.0 mg/dL, Bilirubin, total: Grade 3-4: >3.0 - >10.0 ULN.

  • Number of Participants With Identified Electrocardiogram (ECG) Abnormalities [ Time Frame: Baseline, Weeks 3, 9, 17 and 25, then every 8 weeks until the end of study treatment (up to 17 weeks). ] [ Designated as safety issue: Yes ]
    ECGs were performed and all recordings were evaluated by the investigator. Abnormalities, if present at any study time point, were listed. The following ECG variables were collected: heart rate, PR interval, QRS width, and QT interval. Abnormalities in ECGs were defined by reference to institutional reports.

  • Number of Participants With Abnormal Vital Signs Measurements [ Time Frame: At each study visit (Week 3, 5, 7, 9, 13, 17 and 25) and end of treatment (up to 17 weeks) ] [ Designated as safety issue: Yes ]
    Vital signs included systolic and diastolic blood pressure and heart rate. The investigator used his or her judgement to decide whether or not the values were abnormal.


Enrollment: 55
Study Start Date: December 2006
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Dasatinib
Tablets, Oral, 100 mg, twice daily as long as the patient benefits (avg <6 months)
Other Names:
  • Sprycel
  • BMS-354825
Experimental: 2 Drug: Dasatinib
Tablets, Oral, 70 mg, twice daily as long as the patient benefits (avg <6 months)

  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 or progressive locally advanced, or 'triple negative' metastatic breast cancer
  • paraffin-embedded tissue block must be available
  • measurable disease
  • prior chemotherapy with an anthracycline, a taxane, or both (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 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: NCT00371254

Locations
United States, California
Ucsf-Comprehensive Cancer Center
San Francisco, California, United States, 94143
United States, Florida
Mayo Clinic Jacksonville
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, Texas
University Of Texas Md Anderson Cancer Ctr
Houston, Texas, United States, 77030
France
Local Institution
Paris, France, 75231
Local Institution
Toulouse Cedex 3, France, 31052
Italy
Local Institution
Modena, Italy, 41100
Spain
Local Institution
Barcelona, Spain, 08035
Local Institution
Lleida, Spain, 25198
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: NCT00371254     History of Changes
Other Study ID Numbers: CA180-059
Study First Received: September 1, 2006
Results First Received: October 7, 2010
Last Updated: February 18, 2011
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Triple Negative Breast Neoplasms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014