Breast Cancer, Metastasis
Conditions
Keywords
Recurrent, locally-advanced, or metastatic breast cancer
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
Interventions
DRUGDasatinib
Tablets, Oral, 70 mg, twice daily, as long as the participant benefits (average \<6 months)
DRUGDasatinib 100 mg
Tablets, Oral, 100mg, twice daily, as long as the participant benefits (average \<6 months)
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
| 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. |
| 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. |
Countries
Argentina, Belgium, France, Italy, Peru, Spain, United States
Participant flow
Pre-assignment details
A total of 92 participants were enrolled in the study. Twenty-two participants did not enter the treatment phase, 13 because they did not meet entry criteria and 9 for other reasons. The 70 participants treated in the single-arm were stratified by tumor type into Her2-amplified and ER/PgR positive tumors.
Participants by arm
| Arm | Count |
|---|---|
| Her2/Neu-amplified Tumor Type Participants with a Human epidermal growth factor (Her2/neu)-amplified tumor type (defined as 3+ by immunohistochemistry \[IHC\] or positive by fluorescent or chromogenic in situ hybridization \[FISH or CISH\] regardless of estrogen receptor \[ER\]/progesterone receptor \[PgR\] status) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg. | 24 |
| ER and/or PgR Positive Tumor Type Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg. | 46 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse event(AE Unrelated to Study Drug | 1 | 2 |
| Overall Study | Disease Progression | 21 | 35 |
| Overall Study | Participant Request | 1 | 1 |
| Overall Study | Participant Withdrew Consent | 0 | 1 |
| Overall Study | Study Drug Toxicity | 1 | 7 |
Baseline characteristics
| Characteristic | Her2/Neu-amplified Tumor Type | ER and/or PgR Positive Tumor Type | Total |
|---|---|---|---|
| Age Continuous | 52.2 years | 54.3 years | 53.6 years |
| Age, Customized <=50 years | 8 participants | 16 participants | 24 participants |
| Age, Customized >=50 years | 16 participants | 30 participants | 46 participants |
| Region of Enrollment Argentina | 0 participants | 6 participants | 6 participants |
| Region of Enrollment Belgium | 1 participants | 10 participants | 11 participants |
| Region of Enrollment France | 9 participants | 2 participants | 11 participants |
| Region of Enrollment Italy | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Peru | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Spain | 4 participants | 8 participants | 12 participants |
| Region of Enrollment United States | 10 participants | 17 participants | 27 participants |
| Sex: Female, Male Female | 24 Participants | 46 Participants | 70 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 65 / 70 |
| serious Total, serious adverse events | 20 / 70 |
Outcome results
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.
Time frame: From day of first treatment through Week 25 or at time of discontinuation from study treatment
Population: Evaluable population (n=69): Response Evaluable=treated participants with ≥1 measurable lesion at baseline and ≥1 on-study tumor assessment; Non-responders=treated participants with no on-study tumor response assessment due to rapid disease progression/dasatinib toxicity. One participant was not evaluable (no on-study tumor assessment).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Best Overall Response | Partial Response (PR) | 0 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Best Overall Response | Progressive Disease (PD) | 12 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Best Overall Response | Complete Response (CR) | 0 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Best Overall Response | Unconfirmed partial response | 0 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Best Overall Response | Stable Disease (SD) | 2 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Best Overall Response | Clinical Progression (cPD) | 0 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Best Overall Response | Discontinuation Due To Drug Toxicity (Tox) | 1 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Best Overall Response | No Reassessment -Reasons Other Than Tox/PD | 0 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Best Overall Response | Clinical Progression (cPD) | 1 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Best Overall Response | Stable Disease (SD) | 2 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Best Overall Response | Complete Response (CR) | 0 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Best Overall Response | Progressive Disease (PD) | 4 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Best Overall Response | Partial Response (PR) | 1 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Best Overall Response | No Reassessment -Reasons Other Than Tox/PD | 0 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Best Overall Response | Unconfirmed partial response | 0 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Best Overall Response | Discontinuation Due To Drug Toxicity (Tox) | 1 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Best Overall Response | Complete Response (CR) | 0 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Best Overall Response | Discontinuation Due To Drug Toxicity (Tox) | 5 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Best Overall Response | Unconfirmed partial response | 1 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Best Overall Response | Partial Response (PR) | 1 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Best Overall Response | Stable Disease (SD) | 5 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Best Overall Response | Progressive Disease (PD) | 15 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Best Overall Response | Clinical Progression (cPD) | 3 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Best Overall Response | No Reassessment -Reasons Other Than Tox/PD | 1 participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Best Overall Response | Clinical Progression (cPD) | 1 participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Best Overall Response | Stable Disease (SD) | 3 participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Best Overall Response | Complete Response (CR) | 0 participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Best Overall Response | No Reassessment -Reasons Other Than Tox/PD | 0 participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Best Overall Response | Discontinuation Due To Drug Toxicity (Tox) | 2 participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Best Overall Response | Partial Response (PR) | 1 participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Best Overall Response | Progressive Disease (PD) | 7 participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Best Overall Response | Unconfirmed partial response | 0 participants |
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.
Time frame: From day of first treatment through Week 25 or at time of discontinuation from study treatment.
Population: Evaluable population (n=69): Response Evaluable=treated participants with ≥1 measurable lesion at baseline and ≥1 on-study tumor assessment. One participant was not evaluable (no on-study tumor assessment for other reason).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With Objective Response | 0 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With Objective Response | 1 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Number of Participants With Objective Response | 1 participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Number of Participants With Objective Response | 1 participants |
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.
Time frame: From day of first treatment through Week 25 or at time of discontinuation from study treatment
Population: Evaluable population (n=69): Response Evaluable=treated participants with ≥1 measurable lesion at baseline and ≥1 on-study tumor assessment; Non-responders=treated participants with no on-study tumor response assessment due to rapid disease progression/dasatinib toxicity. One participant was not evaluable (no on-study tumor assessment).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Percentage of Participants With Objective Response | 0 percentage of participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Percentage of Participants With Objective Response | 11.11 percentage of participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Percentage of Participants With Objective Response | 3.23 percentage of participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Percentage of Participants With Objective Response | 7.14 percentage of participants |
| All Response-evaluable Participants | Percentage of Participants With Objective Response | 4.35 percentage of participants |
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.
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
Population: Of 69 response-evaluable participants, three had an objective response of PR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Duration Of Objective Response | 31.14 weeks |
| Her2/Neu-amplified Tumor, 100 mg BID | Duration Of Objective Response | 18.14 weeks |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Duration Of Objective Response | 8.29 weeks |
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.
Time frame: From Baseline (Week 0) to time of PD or discontinuation of last participant from study treatment (Week 45)
Population: All-Treated subjects: All subjects who received at least one dose of dasatinib. The longest on-study observation for a participant was 45 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Median Progression Free Survival (PFS) | 8.1 weeks |
| Her2/Neu-amplified Tumor, 100 mg BID | Median Progression Free Survival (PFS) | 8.1 weeks |
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.
Time frame: From Baseline (Week 0) to time of PD or discontinuation of last participant from study treatment (Week 45)
Population: All-Treated subjects: All subjects who received at least one dose of dasatinib. The longest on-study observation for a participant was 45 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants Who Progressed | 22 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants Who Progressed | 39 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Number of Participants Who Progressed | 61 participants |
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.
Time frame: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug
Population: All-Treated participants: All participants who received at least one dose of dasatinib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With Death, Adverse Events (AEs), and AEs Leading to Discontinuation | All Deaths | 6 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With Death, Adverse Events (AEs), and AEs Leading to Discontinuation | All AEs | 23 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With Death, Adverse Events (AEs), and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 5 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With Death, Adverse Events (AEs), and AEs Leading to Discontinuation | All AEs | 47 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With Death, Adverse Events (AEs), and AEs Leading to Discontinuation | All Deaths | 6 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With Death, Adverse Events (AEs), and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 11 participants |
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.
Time frame: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug
Population: All-Treated participants: All participants who received at least one dose of dasatinib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number Of Participants With Notable Drug-related AEs | Nausea | 8 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number Of Participants With Notable Drug-related AEs | Fatigue | 3 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number Of Participants With Notable Drug-related AEs | Dyspnea | 9 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number Of Participants With Notable Drug-related AEs | Rash | 8 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number Of Participants With Notable Drug-related AEs | Abdominal Pain | 2 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number Of Participants With Notable Drug-related AEs | Pleural Effusion | 9 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number Of Participants With Notable Drug-related AEs | Diarrhea | 10 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number Of Participants With Notable Drug-related AEs | Pleural Effusion | 12 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number Of Participants With Notable Drug-related AEs | Dyspnea | 10 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number Of Participants With Notable Drug-related AEs | Diarrhea | 22 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number Of Participants With Notable Drug-related AEs | Nausea | 16 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number Of Participants With Notable Drug-related AEs | Abdominal Pain | 11 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number Of Participants With Notable Drug-related AEs | Fatigue | 17 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number Of Participants With Notable Drug-related AEs | Rash | 11 participants |
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.
Time frame: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug
Population: All-Treated participants: All participants who received at least one dose of dasatinib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Hemoglobin | 0 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Aspartate Aminotransferase | 1 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Partial Thromboplastin Time | 1 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Creatinine | 1 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Granulocytes | 1 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Hypokalemia | 1 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Alkaline Phosphatase | 0 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Hyponatremia | 0 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Phosphorous | 2 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Platelet Count | 0 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Bilirubin | 0 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Alanine Aminotransferase | 0 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Bilirubin | 1 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Granulocytes | 1 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Hemoglobin | 1 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Platelet Count | 1 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Partial Thromboplastin Time | 0 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Alkaline Phosphatase | 1 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Alanine Aminotransferase | 1 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Aspartate Aminotransferase | 3 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Creatinine | 0 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Hypokalemia | 0 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Phosphorous | 1 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities | Hyponatremia | 1 participants |
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.
Time frame: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug
Population: All-Treated participants: All participants who received at least one dose of dasatinib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs | Drug-related AEs | 22 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs | Drug-related SAEs | 6 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs | SAEs | 9 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs | Drug-related Grade 3 AEs | 9 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs | SAEs | 11 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs | Drug-related AEs | 44 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs | Drug-related Grade 3 AEs | 15 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs | Drug-related SAEs | 7 participants |
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.
Time frame: From day of first treatment through Week 25 or at time of discontinuation from study treatment.
Population: Evaluable population (n=69): Response Evaluable=treated participants with ≥1 measurable lesion at baseline and ≥1 on-study tumor assessment; Non-responders=treated participants with no on-study tumor response assessment due to rapid disease progression/dasatinib toxicity. One participant was not evaluable (no on-study tumor assessment).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with unconfirmed PR (uCR) | 0 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with PR | 0 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Total Participants with DCR | 1 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with CR | 0 participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with SD ≥16 weeks | 1 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with CR | 0 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with unconfirmed PR (uCR) | 0 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Response-evaluable Participants With Disease Control (DCR) | Total Participants with DCR | 1 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with PR | 1 participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with SD ≥16 weeks | 0 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with PR | 1 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with SD ≥16 weeks | 3 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with CR | 0 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with unconfirmed PR (uCR) | 1 participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Total Participants with DCR | 5 participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with CR | 0 participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with SD ≥16 weeks | 1 participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with PR | 1 participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Total Participants with DCR | 2 participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Number of Response-evaluable Participants With Disease Control (DCR) | Participants with unconfirmed PR (uCR) | 0 participants |
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.
Time frame: At Weeks 9, 17, and 25
Population: Evaluable population (n=69): Response Evaluable=treated participants with ≥1 measurable lesion at baseline and ≥1 on-study tumor assessment; Non-responders=treated participants with no on-study tumor response assessment due to rapid disease progression/dasatinib toxicity. One participant was not evaluable (no on-study tumor assessment).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25 | Week 9 | 21 percentage of participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25 | Week 25 | 0 percentage of participants |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25 | Week 17 | 7 percentage of participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25 | Week 9 | 50 percentage of participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25 | Week 25 | 13 percentage of participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25 | Week 17 | 25 percentage of participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25 | Week 17 | 18 percentage of participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25 | Week 9 | 32 percentage of participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25 | Week 25 | 7 percentage of participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25 | Week 9 | 33 percentage of participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25 | Week 25 | 17 percentage of participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25 | Week 17 | 25 percentage of participants |
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.
Time frame: From day of first treatment through Week 25 or at time of discontinuation from study treatment.
Population: Evaluable population (n=69): Response Evaluable=treated participants with ≥1 measurable lesion at baseline and ≥1 on-study tumor assessment; Non-responders=treated participants with no on-study tumor response assessment due to rapid disease progression/dasatinib toxicity. One participant was not evaluable (no on-study tumor assessment).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Percentage of Response-evaluable Participants With Disease Control (DCR) | 6.67 percentage of participants |
| Her2/Neu-amplified Tumor, 100 mg BID | Percentage of Response-evaluable Participants With Disease Control (DCR) | 11.11 percentage of participants |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | Percentage of Response-evaluable Participants With Disease Control (DCR) | 16.13 percentage of participants |
| ER and/or PgR Positive Tumor, 100 mg BID Dasatinib | Percentage of Response-evaluable Participants With Disease Control (DCR) | 14.29 percentage of participants |
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.
Time frame: At Baseline and Week 3 of treatment (Day 15 ±4 days)
Population: Number of Participants Analyzed=All Treated Participants with samples for PD analysis, n=number of participants at specified time point with samples for PD analysis
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 3 in Participants With and Without DCR | Participants with no DCR (n=27, n=16) | 32.07 percent change |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 3 in Participants With and Without DCR | Participants with DCR (n=2, n=3) | 22.01 percent change |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 3 in Participants With and Without DCR | All Participants (n=29, n=19) | 31.35 percent change |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 3 in Participants With and Without DCR | Participants with no DCR (n=27, n=16) | 35.92 percent change |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 3 in Participants With and Without DCR | Participants with DCR (n=2, n=3) | 40.74 percent change |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 3 in Participants With and Without DCR | All Participants (n=29, n=19) | 36.67 percent change |
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.
Time frame: Week 5
Population: Number of Participants Analyzed=All Treated Participants with samples for PD analysis, n=number of participants at specified time point with samples for PD analysis
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 5 in Participants With and Without DCR | All Participants (n=23, n=15) | 41.33 percent change |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 5 in Participants With and Without DCR | Participants with no DCR (n=20, n=12) | 45.37 percent change |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 5 in Participants With and Without DCR | Participants with DCR (n=3, n=3) | 17.13 percent change |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 5 in Participants With and Without DCR | All Participants (n=23, n=15) | 34.97 percent change |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 5 in Participants With and Without DCR | Participants with no DCR (n=20, n=12) | 28.45 percent change |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 5 in Participants With and Without DCR | Participants with DCR (n=3, n=3) | 64.51 percent change |
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.
Time frame: At Baseline and Week 3 of treatment (Day 15 ±4 days)
Population: Number of Participants Analyzed=All Treated Participants with samples for PD analysis, n=number of participants at specified time point with samples for PD analysis
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 3 in Participants With and Without DCR | Participants with no DCR (n=27, n=16) | 21.88 percent change |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 3 in Participants With and Without DCR | Participants with DCR (n=2, n=3) | 14.77 percent change |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 3 in Participants With and Without DCR | All Participants (n=29, n=19) | 21.37 percent change |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 3 in Participants With and Without DCR | Participants with no DCR (n=27, n=16) | 23.61 percent change |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 3 in Participants With and Without DCR | Participants with DCR (n=2, n=3) | -5.03 percent change |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 3 in Participants With and Without DCR | All Participants (n=29, n=19) | 18.57 percent change |
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.
Time frame: At Baseline and Week 5 of treatment
Population: Number of Participants Analyzed=All Treated Participants with samples for PD analysis, n=number of participants at specified time point with samples for PD analysis
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 5 in Participants With and Without DCR | Participants with DCR (n=3, n=3) | 16.46 percent change |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 5 in Participants With and Without DCR | All Participants (n=23, n=15) | 25.77 percent change |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 5 in Participants With and Without DCR | Participants with no DCR (n=20, n=12) | 27.23 percent change |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 5 in Participants With and Without DCR | Participants with no DCR (n=20, n=12) | 26.36 percent change |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 5 in Participants With and Without DCR | Participants with DCR (n=3, n=3) | 37.25 percent change |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 5 in Participants With and Without DCR | All Participants (n=23, n=15) | 28.47 percent change |
Secondary
Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3
Blood samples (3 mL) were used for measurement of dasatinib plasma concentration and metabolites.
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).
Population: Number of Participants Analyzed=All Treated Participants with samples for PK analysis, n=number of participants at specified time point with samples for PK analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3 | Time 1 hour (100 mg, n=16; 70 mg, n=14) | 107.09 ng/ml | Standard Deviation 64.55 |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3 | Time 6 hours (100 mg, n=17; 70 mg, n=13) | 23.19 ng/ml | Standard Deviation 15.2 |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3 | Time 3 hours (100 mg, n=17; 70 mg, n=14) | 58.01 ng/ml | Standard Deviation 37.88 |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3 | Time 12 hours (100 mg, n=16; 70 mg, n=9) | 11.88 ng/ml | Standard Deviation 6.4 |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3 | Time 0 hours (100 mg, n=16; 70 mg, n=13) | 10.82 ng/ml | Standard Deviation 9.17 |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3 | Time 12 hours (100 mg, n=16; 70 mg, n=9) | 7.41 ng/ml | Standard Deviation 5.08 |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3 | Time 0 hours (100 mg, n=16; 70 mg, n=13) | 6.96 ng/ml | Standard Deviation 2.9 |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3 | Time 1 hour (100 mg, n=16; 70 mg, n=14) | 77.21 ng/ml | Standard Deviation 61.86 |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3 | Time 3 hours (100 mg, n=17; 70 mg, n=14) | 30.21 ng/ml | Standard Deviation 18.42 |
| Her2/Neu-amplified Tumor, 100 mg BID | Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3 | Time 6 hours (100 mg, n=17; 70 mg, n=13) | 12.64 ng/ml | Standard Deviation 5.58 |
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.
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).
Population: Number of Participants Analyzed=All Treated Participants with samples for PK analysis, n=number of participants at specified time point with samples for PK analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 0 hours (100 mg, n=5; 70 mg, n=7; 50 mg, n=1) | 9.49 ng/ml | Standard Deviation 4.94 |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 6 hours (100 mg, n=5; 70 mg, n=8; 50 mg, n=1) | 23.58 ng/ml | Standard Deviation 8.65 |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 3 hours (100 mg, n=5; 70 mg, n=9; 50 mg, n=1) | 55.26 ng/ml | Standard Deviation 23.65 |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 12 hours (100 mg, n=4; 70 mg, n=6; 50 mg, n=1 | 10.52 ng/ml | Standard Deviation 3.55 |
| Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 1 hour (100 mg, n=5; 70 mg, n=8; 50 mg, n=1) | 131.09 ng/ml | Standard Deviation 57.52 |
| Her2/Neu-amplified Tumor, 100 mg BID | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 3 hours (100 mg, n=5; 70 mg, n=9; 50 mg, n=1) | 42.27 ng/ml | Standard Deviation 21.94 |
| Her2/Neu-amplified Tumor, 100 mg BID | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 0 hours (100 mg, n=5; 70 mg, n=7; 50 mg, n=1) | 6.62 ng/ml | Standard Deviation 3.54 |
| Her2/Neu-amplified Tumor, 100 mg BID | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 1 hour (100 mg, n=5; 70 mg, n=8; 50 mg, n=1) | 49.28 ng/ml | Standard Deviation 37.97 |
| Her2/Neu-amplified Tumor, 100 mg BID | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 6 hours (100 mg, n=5; 70 mg, n=8; 50 mg, n=1) | 13.03 ng/ml | Standard Deviation 3.34 |
| Her2/Neu-amplified Tumor, 100 mg BID | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 12 hours (100 mg, n=4; 70 mg, n=6; 50 mg, n=1 | 5.00 ng/ml | Standard Deviation 2.26 |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 12 hours (100 mg, n=4; 70 mg, n=6; 50 mg, n=1 | 9.02 ng/ml | Standard Deviation 0 |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 6 hours (100 mg, n=5; 70 mg, n=8; 50 mg, n=1) | 35.91 ng/ml | Standard Deviation 0 |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 0 hours (100 mg, n=5; 70 mg, n=7; 50 mg, n=1) | 6.06 ng/ml | Standard Deviation 0 |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 3 hours (100 mg, n=5; 70 mg, n=9; 50 mg, n=1) | 35.74 ng/ml | Standard Deviation 0 |
| ER and/or PgR Positive Tumor, 70 mg BID Dasatinib | PK: Plasma Concentration of Dasatinib at Week 7 or Week 9 | Time 1 hour (100 mg, n=5; 70 mg, n=8; 50 mg, n=1) | 4.75 ng/ml | Standard Deviation 0 |