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

Phase II Study of Dasatinib (BMS-354825) for Advanced Estrogen/Progesterone Receptor-Positive or Her2/Neu-Positive Breast Cancer

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

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Metastasis
• Intervention / Treatment: Drug: Dasatinib; Drug: Dasatinib 100 mg

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: BMS-354825; Sprycel; Drug: Dasatinib 100 mg; Tablets, Oral, 100mg, twice daily, as long as the participant benefits (average <6 months); Other Names: BMS-354825; Sprycel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Objective Response	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.	From day of first treatment through Week 25 or at time of discontinuation from study treatment.
Percentage of Participants With Objective Response	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.	From day of first treatment through Week 25 or at time of discontinuation from study treatment
Best Overall Response	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.	From day of first treatment through Week 25 or at time of discontinuation from study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Response-evaluable Participants With Disease Control (DCR)	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.	From day of first treatment through Week 25 or at time of discontinuation from study treatment.
Percentage of Response-evaluable Participants With Disease Control (DCR)	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.	From day of first treatment through Week 25 or at time of discontinuation from study treatment.
Number of Participants Who Progressed	PFS was defined as time from first dosing date until the first date that Progressive Disease (PD) was observed.	From Baseline (Week 0) to time of PD or discontinuation of last participant from study treatment (Week 45)
Median Progression Free Survival (PFS)	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.	From Baseline (Week 0) to time of PD or discontinuation of last participant from study treatment (Week 45)
Percentage of Participants With Progression-free Survival (PFS) 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.	At Weeks 9, 17, and 25
Duration Of Objective Response	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.	the time (in weeks) between the first date that criteria for PR were met and the first date that PD or cPD was observed
Number of Participants With Death, Adverse Events (AEs), and AEs Leading to Discontinuation	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.	Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug
Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities	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.	Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug
Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs	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.	Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug
Number Of Participants With Notable Drug-related AEs	Notable drug-related AEs for dasatinib include gastrointestinal symptoms (diarrhea, nausea, vomiting and abdominal pain), fatigue, lethargy, headache, rash, fever, pleural effusion, and dyspnea.	Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug
Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3	Blood samples (3 mL) were used for measurement of dasatinib plasma concentration and metabolites.	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).
PK: Plasma Concentration of Dasatinib at Week 7 or Week 9	Blood samples (3 mL) were used for measurement of dasatinib plasma concentration and metabolites.	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).
Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 3 in Participants With and Without DCR	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.	At Baseline and Week 3 of treatment (Day 15 ±4 days)
Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 5 in Participants With and Without DCR	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.	Week 5
Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 3 in Participants With and Without DCR	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.	At Baseline and Week 3 of treatment (Day 15 ±4 days)
Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 5 in Participants With and Without DCR	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.	At Baseline and Week 5 of treatment

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: September 1, 2006
• First Submitted That Met QC Criteria: September 1, 2006
• First Posted (Estimate): September 4, 2006

Study Record Updates

• Last Update Posted (Estimate): April 26, 2011
• Last Update Submitted That Met QC Criteria: April 21, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Recurrent, locally-advanced, or metastatic breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: CA180-088