Trial Outcomes & Findings for Study of Dasatinib (BMS-354825) in Patients With Advanced Estrogen/Progesterone Receptor-positive (ER+/PR+) or Her2/Neu-positive (Her2/Neu+)Breast Cancer (NCT NCT00371345)
NCT ID: NCT00371345
Last Updated: 2011-04-26
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
92 participants
Primary outcome timeframe
From day of first treatment through Week 25 or at time of discontinuation from study treatment.
Results posted on
2011-04-26
Participant Flow
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.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
24
|
46
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
24
|
46
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Disease Progression
|
21
|
35
|
|
Overall Study
Study Drug Toxicity
|
1
|
7
|
|
Overall Study
Adverse event(AE Unrelated to Study Drug
|
1
|
2
|
|
Overall Study
Participant Request
|
1
|
1
|
|
Overall Study
Participant Withdrew Consent
|
0
|
1
|
Baseline Characteristics
Study of Dasatinib (BMS-354825) in Patients With Advanced Estrogen/Progesterone Receptor-positive (ER+/PR+) or Her2/Neu-positive (Her2/Neu+)Breast Cancer
Baseline characteristics by cohort
| Measure |
Her2/Neu-amplified Tumor Type
n=24 Participants
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.
|
ER and/or PgR Positive Tumor Type
n=46 Participants
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.
|
Total
n=70 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
52.2 years
n=5 Participants
|
54.3 years
n=7 Participants
|
53.6 years
n=5 Participants
|
|
Age, Customized
<=50 years
|
8 participants
n=5 Participants
|
16 participants
n=7 Participants
|
24 participants
n=5 Participants
|
|
Age, Customized
>=50 years
|
16 participants
n=5 Participants
|
30 participants
n=7 Participants
|
46 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
70 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
9 participants
n=5 Participants
|
2 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
17 participants
n=7 Participants
|
27 participants
n=5 Participants
|
|
Region of Enrollment
Argentina
|
0 participants
n=5 Participants
|
6 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
4 participants
n=5 Participants
|
8 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
1 participants
n=5 Participants
|
10 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Region of Enrollment
Peru
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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).
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.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=15 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=9 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
n=31 Participants
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
n=14 Participants
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
Number of Participants With Objective Response
|
0 participants
|
1 participants
|
1 participants
|
1 participants
|
—
|
PRIMARY outcome
Timeframe: From day of first treatment through Week 25 or at time of discontinuation from study treatmentPopulation: 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).
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.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=15 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=9 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
n=31 Participants
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
n=14 Participants
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.
|
All Response-evaluable Participants
n=69 Participants
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).
|
|---|---|---|---|---|---|
|
Percentage of Participants With Objective Response
|
0 percentage of participants
Interval 0.0 to 0.0
|
11.11 percentage of participants
Interval 0.28 to 48.25
|
3.23 percentage of participants
Interval 0.08 to 16.7
|
7.14 percentage of participants
Interval 0.18 to 33.87
|
4.35 percentage of participants
Interval 0.91 to 12.18
|
PRIMARY outcome
Timeframe: From day of first treatment through Week 25 or at time of discontinuation from study treatmentPopulation: 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).
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.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=15 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=9 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
n=31 Participants
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
n=14 Participants
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
Best Overall Response
Progressive Disease (PD)
|
12 participants
|
4 participants
|
15 participants
|
7 participants
|
—
|
|
Best Overall Response
Stable Disease (SD)
|
2 participants
|
2 participants
|
5 participants
|
3 participants
|
—
|
|
Best Overall Response
Clinical Progression (cPD)
|
0 participants
|
1 participants
|
3 participants
|
1 participants
|
—
|
|
Best Overall Response
Discontinuation Due To Drug Toxicity (Tox)
|
1 participants
|
1 participants
|
5 participants
|
2 participants
|
—
|
|
Best Overall Response
No Reassessment -Reasons Other Than Tox/PD
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Best Overall Response
Complete Response (CR)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Best Overall Response
Unconfirmed partial response
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Best Overall Response
Partial Response (PR)
|
0 participants
|
1 participants
|
1 participants
|
1 participants
|
—
|
SECONDARY outcome
Timeframe: 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).
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.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=1 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=1 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
n=5 Participants
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
n=2 Participants
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
Number of Response-evaluable Participants With Disease Control (DCR)
Participants with CR
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
—
|
|
Number of Response-evaluable Participants With Disease Control (DCR)
Participants with unconfirmed PR (uCR)
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
—
|
|
Number of Response-evaluable Participants With Disease Control (DCR)
Participants with PR
|
0 participants
|
1 participants
|
1 participants
|
1 participants
|
—
|
|
Number of Response-evaluable Participants With Disease Control (DCR)
Participants with SD ≥16 weeks
|
1 participants
|
0 participants
|
3 participants
|
1 participants
|
—
|
|
Number of Response-evaluable Participants With Disease Control (DCR)
Total Participants with DCR
|
1 participants
|
1 participants
|
5 participants
|
2 participants
|
—
|
SECONDARY outcome
Timeframe: 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).
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.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=15 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=9 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
n=31 Participants
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
n=14 Participants
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
Percentage of Response-evaluable Participants With Disease Control (DCR)
|
6.67 percentage of participants
Interval 0.17 to 31.95
|
11.11 percentage of participants
Interval 0.28 to 48.25
|
16.13 percentage of participants
Interval 5.54 to 33.73
|
14.29 percentage of participants
Interval 1.78 to 42.81
|
—
|
SECONDARY outcome
Timeframe: 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.
PFS was defined as time from first dosing date until the first date that Progressive Disease (PD) was observed.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=24 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=46 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
n=70 Participants
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
Number of Participants Who Progressed
|
22 participants
|
39 participants
|
61 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=24 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=46 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
Median Progression Free Survival (PFS)
|
8.1 weeks
Interval 7.1 to 9.3
|
8.1 weeks
Interval 7.7 to 8.7
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At Weeks 9, 17, and 25Population: 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).
PFS was defined as time from first dosing date until the first date that progressive disease (PD) was observed.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=15 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=9 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
n=32 Participants
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
n=14 Participants
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25
Week 9
|
21 percentage of participants
|
50 percentage of participants
|
32 percentage of participants
|
33 percentage of participants
|
—
|
|
Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25
Week 17
|
7 percentage of participants
|
25 percentage of participants
|
18 percentage of participants
|
25 percentage of participants
|
—
|
|
Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25
Week 25
|
0 percentage of participants
|
13 percentage of participants
|
7 percentage of participants
|
17 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: the time (in weeks) between the first date that criteria for PR were met and the first date that PD or cPD was observedPopulation: Of 69 response-evaluable participants, three had an objective response of PR.
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.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=1 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=1 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
n=1 Participants
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
Duration Of Objective Response
|
31.14 weeks
|
18.14 weeks
|
8.29 weeks
|
—
|
—
|
SECONDARY outcome
Timeframe: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drugPopulation: All-Treated participants: All participants who received at least one dose of dasatinib.
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.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=23 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=47 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
Number of Participants With Death, Adverse Events (AEs), and AEs Leading to Discontinuation
All Deaths
|
6 participants
|
6 participants
|
—
|
—
|
—
|
|
Number of Participants With Death, Adverse Events (AEs), and AEs Leading to Discontinuation
All AEs
|
23 participants
|
47 participants
|
—
|
—
|
—
|
|
Number of Participants With Death, Adverse Events (AEs), and AEs Leading to Discontinuation
AEs Leading to Discontinuation
|
5 participants
|
11 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drugPopulation: All-Treated participants: All participants who received at least one dose of dasatinib.
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.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=23 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=47 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities
Platelet Count
|
0 participants
|
1 participants
|
—
|
—
|
—
|
|
Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities
Partial Thromboplastin Time
|
1 participants
|
0 participants
|
—
|
—
|
—
|
|
Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities
Alkaline Phosphatase
|
0 participants
|
1 participants
|
—
|
—
|
—
|
|
Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities
Alanine Aminotransferase
|
0 participants
|
1 participants
|
—
|
—
|
—
|
|
Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities
Hyponatremia
|
0 participants
|
1 participants
|
—
|
—
|
—
|
|
Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities
Bilirubin
|
0 participants
|
1 participants
|
—
|
—
|
—
|
|
Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities
Granulocytes
|
1 participants
|
1 participants
|
—
|
—
|
—
|
|
Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities
Hemoglobin
|
0 participants
|
1 participants
|
—
|
—
|
—
|
|
Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities
Aspartate Aminotransferase
|
1 participants
|
3 participants
|
—
|
—
|
—
|
|
Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities
Creatinine
|
1 participants
|
0 participants
|
—
|
—
|
—
|
|
Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities
Hypokalemia
|
1 participants
|
0 participants
|
—
|
—
|
—
|
|
Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities
Phosphorous
|
2 participants
|
1 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drugPopulation: All-Treated participants: All participants who received at least one dose of dasatinib.
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.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=23 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=47 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs
Drug-related AEs
|
22 participants
|
44 participants
|
—
|
—
|
—
|
|
Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs
SAEs
|
9 participants
|
11 participants
|
—
|
—
|
—
|
|
Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs
Drug-related SAEs
|
6 participants
|
7 participants
|
—
|
—
|
—
|
|
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
|
15 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drugPopulation: All-Treated participants: All participants who received at least one dose of dasatinib.
Notable drug-related AEs for dasatinib include gastrointestinal symptoms (diarrhea, nausea, vomiting and abdominal pain), fatigue, lethargy, headache, rash, fever, pleural effusion, and dyspnea.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=23 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=47 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
Number Of Participants With Notable Drug-related AEs
Pleural Effusion
|
9 participants
|
12 participants
|
—
|
—
|
—
|
|
Number Of Participants With Notable Drug-related AEs
Dyspnea
|
9 participants
|
10 participants
|
—
|
—
|
—
|
|
Number Of Participants With Notable Drug-related AEs
Diarrhea
|
10 participants
|
22 participants
|
—
|
—
|
—
|
|
Number Of Participants With Notable Drug-related AEs
Nausea
|
8 participants
|
16 participants
|
—
|
—
|
—
|
|
Number Of Participants With Notable Drug-related AEs
Abdominal Pain
|
2 participants
|
11 participants
|
—
|
—
|
—
|
|
Number Of Participants With Notable Drug-related AEs
Fatigue
|
3 participants
|
17 participants
|
—
|
—
|
—
|
|
Number Of Participants With Notable Drug-related AEs
Rash
|
8 participants
|
11 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 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
Blood samples (3 mL) were used for measurement of dasatinib plasma concentration and metabolites.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=17 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=14 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
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
|
6.96 ng/ml
Standard Deviation 2.90
|
—
|
—
|
—
|
|
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
|
77.21 ng/ml
Standard Deviation 61.86
|
—
|
—
|
—
|
|
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
|
30.21 ng/ml
Standard Deviation 18.42
|
—
|
—
|
—
|
|
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 15.20
|
12.64 ng/ml
Standard Deviation 5.58
|
—
|
—
|
—
|
|
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 6.40
|
7.41 ng/ml
Standard Deviation 5.08
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 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
Blood samples (3 mL) were used for measurement of dasatinib plasma concentration and metabolites.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=5 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=9 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
n=1 Participants
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
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
|
13.03 ng/ml
Standard Deviation 3.34
|
35.91 ng/ml
Standard Deviation 0.00
|
—
|
—
|
|
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
|
5.00 ng/ml
Standard Deviation 2.26
|
9.02 ng/ml
Standard Deviation 0.00
|
—
|
—
|
|
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
|
6.62 ng/ml
Standard Deviation 3.54
|
6.06 ng/ml
Standard Deviation 0.00
|
—
|
—
|
|
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
|
49.28 ng/ml
Standard Deviation 37.97
|
4.75 ng/ml
Standard Deviation 0.00
|
—
|
—
|
|
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
|
42.27 ng/ml
Standard Deviation 21.94
|
35.74 ng/ml
Standard Deviation 0.00
|
—
|
—
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=29 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=19 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
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
Interval 23.58 to 41.15
|
35.92 percent change
Interval 25.72 to 46.94
|
—
|
—
|
—
|
|
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
Interval 11.21 to 33.87
|
40.74 percent change
Interval 10.81 to 78.75
|
—
|
—
|
—
|
|
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
Interval 23.46 to 39.76
|
36.67 percent change
Interval 27.74 to 46.21
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 5Population: 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
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.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=23 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=15 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
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
Interval 33.43 to 58.38
|
28.45 percent change
Interval -2.25 to 68.8
|
—
|
—
|
—
|
|
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
Interval -11.57 to 55.14
|
64.51 percent change
Interval 34.18 to 101.68
|
—
|
—
|
—
|
|
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
Interval 30.41 to 53.18
|
34.97 percent change
Interval 8.48 to 67.92
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 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
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.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=29 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=15 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
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
Interval 15.98 to 28.08
|
23.61 percent change
Interval 20.41 to 27.17
|
—
|
—
|
—
|
|
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
Interval 6.25 to 23.97
|
-5.03 percent change
Interval -55.67 to 103.43
|
—
|
—
|
—
|
|
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
Interval 15.88 to 27.13
|
18.57 percent change
Interval 9.95 to 27.86
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At Baseline and Week 5 of treatmentPopulation: 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
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.
Outcome measures
| Measure |
Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib
n=23 Participants
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 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
Her2/Neu-amplified Tumor, 100 mg BID
n=15 Participants
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.
|
ER and/or PgR Positive Tumor, 70 mg BID Dasatinib
Participants with ER and/or PgR positive tumor types (defined as \>10% of cells positive by IHC \[unless Her2/neu-amplified\]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
|
ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
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.
|
All Response-evaluable Participants
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).
|
|---|---|---|---|---|---|
|
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
Interval 22.53 to 32.1
|
26.36 percent change
Interval 20.85 to 32.13
|
—
|
—
|
—
|
|
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
Interval 8.27 to 25.27
|
37.25 percent change
Interval 23.08 to 53.05
|
—
|
—
|
—
|
|
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
Interval 21.51 to 30.18
|
28.47 percent change
Interval 23.48 to 33.66
|
—
|
—
|
—
|
Adverse Events
Dasatinib
Serious events: 20 serious events
Other events: 65 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dasatinib
n=70 participants at risk
Dasatinib was administered orally at 70 mg BID (TDD=140 mg) or 100 mg BID (TDD=200 mg).
|
|---|---|
|
Investigations
WEIGHT INCREASED
|
1.4%
1/70
|
|
Nervous system disorders
HEADACHE
|
2.9%
2/70
|
|
Nervous system disorders
HEMIPARESIS
|
1.4%
1/70
|
|
Nervous system disorders
BRAIN OEDEMA
|
1.4%
1/70
|
|
Gastrointestinal disorders
NAUSEA
|
2.9%
2/70
|
|
Gastrointestinal disorders
VOMITING
|
1.4%
1/70
|
|
Gastrointestinal disorders
DIARRHOEA
|
2.9%
2/70
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
1.4%
1/70
|
|
Gastrointestinal disorders
ABDOMINAL PAIN LOWER
|
1.4%
1/70
|
|
Infections and infestations
PNEUMONIA
|
1.4%
1/70
|
|
Infections and infestations
SINUSITIS
|
1.4%
1/70
|
|
Infections and infestations
LOBAR PNEUMONIA
|
1.4%
1/70
|
|
Renal and urinary disorders
RENAL FAILURE ACUTE
|
1.4%
1/70
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
1.4%
1/70
|
|
Metabolism and nutrition disorders
FLUID RETENTION
|
1.4%
1/70
|
|
Skin and subcutaneous tissue disorders
SWELLING FACE
|
1.4%
1/70
|
|
Injury, poisoning and procedural complications
FALL
|
1.4%
1/70
|
|
Injury, poisoning and procedural complications
TOOTH INJURY
|
1.4%
1/70
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
1.4%
1/70
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
1.4%
1/70
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
1.4%
1/70
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
4.3%
3/70
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
7.1%
5/70
|
|
Respiratory, thoracic and mediastinal disorders
PRODUCTIVE COUGH
|
1.4%
1/70
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
1.4%
1/70
|
|
General disorders
FATIGUE
|
2.9%
2/70
|
|
General disorders
PYREXIA
|
1.4%
1/70
|
|
General disorders
OEDEMA PERIPHERAL
|
1.4%
1/70
|
|
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION
|
4.3%
3/70
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT NEOPLASM PROGRESSION
|
1.4%
1/70
|
Other adverse events
| Measure |
Dasatinib
n=70 participants at risk
Dasatinib was administered orally at 70 mg BID (TDD=140 mg) or 100 mg BID (TDD=200 mg).
|
|---|---|
|
Eye disorders
LACRIMATION INCREASED
|
5.7%
4/70
|
|
Investigations
WEIGHT DECREASED
|
11.4%
8/70
|
|
Investigations
HAEMOGLOBIN DECREASED
|
5.7%
4/70
|
|
Investigations
ALANINE AMINOTRANSFERASE
|
7.1%
5/70
|
|
Investigations
ASPARTATE AMINOTRANSFERASE
|
5.7%
4/70
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
14.3%
10/70
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
17.1%
12/70
|
|
Investigations
BLOOD ALKALINE PHOSPHATASE INCREASED
|
8.6%
6/70
|
|
Cardiac disorders
PERICARDIAL EFFUSION
|
10.0%
7/70
|
|
Psychiatric disorders
INSOMNIA
|
5.7%
4/70
|
|
Nervous system disorders
HEADACHE
|
40.0%
28/70
|
|
Nervous system disorders
DIZZINESS
|
7.1%
5/70
|
|
Gastrointestinal disorders
NAUSEA
|
37.1%
26/70
|
|
Gastrointestinal disorders
VOMITING
|
24.3%
17/70
|
|
Gastrointestinal disorders
DIARRHOEA
|
48.6%
34/70
|
|
Gastrointestinal disorders
DYSPEPSIA
|
5.7%
4/70
|
|
Gastrointestinal disorders
CONSTIPATION
|
10.0%
7/70
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
21.4%
15/70
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
5.7%
4/70
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
12.9%
9/70
|
|
Metabolism and nutrition disorders
ANOREXIA
|
24.3%
17/70
|
|
Blood and lymphatic system disorders
ANAEMIA
|
8.6%
6/70
|
|
Skin and subcutaneous tissue disorders
RASH
|
27.1%
19/70
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
5.7%
4/70
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
8.6%
6/70
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
7.1%
5/70
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
14.3%
10/70
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
7.1%
5/70
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
15.7%
11/70
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
34.3%
24/70
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
27.1%
19/70
|
|
General disorders
CHILLS
|
8.6%
6/70
|
|
General disorders
FATIGUE
|
27.1%
19/70
|
|
General disorders
PYREXIA
|
20.0%
14/70
|
|
General disorders
ASTHENIA
|
34.3%
24/70
|
|
General disorders
CHEST PAIN
|
7.1%
5/70
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER