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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00371345
• Other study ID #: CA180-088
• Status: Completed
• Phase: Phase 2
• First received: September 1, 2006
• Last updated: April 21, 2011
• Start date: December 2006
• Est. completion date: May 2009

Study information

• Verified date: April 2011
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: May 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Metastasis

Intervention

Drug:
• Dasatinib
Tablets, Oral, 70 mg, twice daily, as long as the participant benefits (average <6 months)
• Dasatinib 100 mg
Tablets, Oral, 100mg, twice daily, as long as the participant benefits (average <6 months)

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Haedo	Buenos Aires
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Bruxelles
France	Local Institution	Dijon Cedex
France	Local Institution	Paris
France	Local Institution	Saint Herblain Cedex
France	Local Institution	Toulouse Cedex 3
Italy	Local Institution	Modena
Peru	Local Institution	Arequipa
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Spain	Local Institution	Barcelona
Spain	Local Institution	Lleida
Spain	Local Institution	Madrid
United States	Dana-Farber Cancer Inst	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	University Of North Carolina At Chapel Hill	Chapel Hill	North Carolina
United States	University Of Texas Md Anderson Cancer Ctr	Houston	Texas
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Ucsf-Comprehensive Cancer Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  France,  Italy,  Peru,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Primary	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	No
Primary	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	No
Secondary	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.	No
Secondary	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.	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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).	No
Secondary	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).	No
Secondary	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)	No
Secondary	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	No
Secondary	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)	No
Secondary	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	No

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