Study of Dasatinib (BMS-354825) in Patients With Advanced Estrogen/Progesterone Receptor-positive (ER+/PR+) or Her2/Neu-positive (Her2/Neu+)Breast Cancer
- Registration Number
- NCT00371345
- Lead Sponsor
- Bristol-Myers Squibb
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 92
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dasatinib Dasatinib 100 mg 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). Dasatinib 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).
- Primary Outcome Measures
Name Time Method Number of Participants With Objective Response 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 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 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.
- Secondary Outcome Measures
Name Time Method Number of Response-evaluable Participants With Disease Control (DCR) 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) 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 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) 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 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 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 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 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 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 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 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 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 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 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 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 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.
Trial Locations
- Locations (8)
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
Ucsf-Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
University Of Texas Md Anderson Cancer Ctr
🇺🇸Houston, Texas, United States
Local Institution
🇪🇸Madrid, Spain
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Dana-Farber Cancer Inst
🇺🇸Boston, Massachusetts, United States
University Of North Carolina At Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States