Trial Outcomes & Findings for A Study of Dasatinib (BMS-354825) in Patients With Advanced 'Triple-negative' Breast Cancer (NCT NCT00371254)
NCT ID: NCT00371254
Last Updated: 2011-03-15
Results Overview
Tumor response was defined as the number of participants whose best response was CR or PR, per the Response Evaluation Criteria in Solid Tumor (RECIST): CR: disappearance of all target/non-target lesions; PR: \>= 30% decrease in the sum of the LDs of target lesions relative to the baseline sum LD.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
55 participants
Primary outcome timeframe
Baseline to end of study drug therapy (up to 65 weeks).
Results posted on
2011-03-15
Participant Flow
55 participants were enrolled in the study; 11 discontinued prior to study drug administration (8 no longer met study criteria, 2 other reasons and 1 administrative reason by the sponsor)
Participant milestones
| Measure |
Dasatinib 100 mg BID
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|
|
Overall Study
STARTED
|
23
|
21
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
23
|
21
|
Reasons for withdrawal
| Measure |
Dasatinib 100 mg BID
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|
|
Overall Study
Disease progression
|
13
|
13
|
|
Overall Study
Study drug toxicity
|
3
|
5
|
|
Overall Study
Subject request
|
5
|
0
|
|
Overall Study
Investigator Decision
|
2
|
0
|
|
Overall Study
Adverse event unrelated to study drug
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
A Study of Dasatinib (BMS-354825) in Patients With Advanced 'Triple-negative' Breast Cancer
Baseline characteristics by cohort
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=21 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Total
n=44 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Race/Ethnicity, Customized
White
|
20 participants
n=5 Participants
|
19 participants
n=7 Participants
|
39 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown or Not Reported
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Age, Customized
<50 years
|
4 participants
n=5 Participants
|
9 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Age, Customized
>=50 years
|
19 participants
n=5 Participants
|
12 participants
n=7 Participants
|
31 participants
n=5 Participants
|
|
Age Continuous
|
56.4 years
STANDARD_DEVIATION 8.98 • n=5 Participants
|
51.5 years
STANDARD_DEVIATION 9.34 • n=7 Participants
|
54.0 years
STANDARD_DEVIATION 9.38 • n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
11 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to end of study drug therapy (up to 65 weeks).Population: All response-evaluable participants i.e. all treated participants who had at least 1 measurable lesion at baseline, had at least 1 on-study tumor assessment or discontinued before any on-study tumor assessment for reasons related to disease or study drug.
Tumor response was defined as the number of participants whose best response was CR or PR, per the Response Evaluation Criteria in Solid Tumor (RECIST): CR: disappearance of all target/non-target lesions; PR: \>= 30% decrease in the sum of the LDs of target lesions relative to the baseline sum LD.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=20 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Number of Participants With Complete Response (CR) or Partial Response (PR)
|
2 participants
|
0 participants
|
—
|
PRIMARY outcome
Timeframe: Baseline to end of study drug therapy (up to 65 weeks).Population: All response-evaluable participants i.e. all treated participants who had at least 1 measurable lesion at baseline, 1 on-study tumor assessment or discontinued before any on-study tumor assessment for reasons related to disease or study drug were included in this dataset.
The percentage of participants whose best response was CR or PR, per the RECIST: CR: disappearance of all target/non-target lesions; PR: \>= 30% decrease in the sum of the LDs of target lesions relative to the baseline sum LD.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=20 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Percentage of Participants With Complete Response (CR) or Partial Response (PR)
|
8.7 percentage of participants
Interval 1.07 to 28.04
|
0.0 percentage of participants
Interval 0.0 to 0.0
|
—
|
SECONDARY outcome
Timeframe: Baseline to 16 weeks.Population: All response-evaluable participants i.e. all treated participants who had at least 1 measurable lesion at baseline, had at least 1 on-study tumor assessment or discontinued before any on-study tumor assessment for reasons related to disease or study drug.
The number of participants whose best response was CR, PR or SD (per the RECIST) at or after 16 weeks on study: CR: disappearance of all target/non-target lesions; PR: \>=30% decrease in the sum of the LDs of target lesions relative to baseline sum LD; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PD: appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=20 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study
|
3 Participants
|
1 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline to 16 weeksPopulation: All response-evaluable participants i.e. all treated participants who had at least 1 measurable lesion at baseline, had at least 1 on-study tumor assessment or discontinued before any on-study tumor assessment for reasons related to disease or study drug.
The percentage of participants whose best response was CR, PR or SD (per the RECIST) at or after 16 weeks on study: CR: disappearance of all target/non-target lesions; PR: \>=30% decrease in the sum of the LDs of target lesions relative to baseline sum LD; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PD: appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=20 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Percentage of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study
|
13.04 percentage of participants
Interval 2.78 to 33.59
|
5.0 percentage of participants
Interval 0.13 to 24.87
|
—
|
SECONDARY outcome
Timeframe: Weeks 9, 17, and 25Population: All treated participants
PFS:time from first dose until the date that progressive disease (PD) or clinical PD (cPD) observed,per RECIST criteria.PD:appearance of new lesion/s,or \>=20% increase in the sum of the LD of target lesions,relative to smallest sum LD recorded since treatment start,or unequivocal progression of existing non-target lesions;cPD:deterioration related to disease requiring treatment discontinuation,but without radiographic PD.Participants who died without PD were considered to have PD on the date of death.For participants who neither progressed nor died,date of the last tumor assessment was used.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=21 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Proportion of Participants With Progression-Free Survival (PFS) at Weeks 9, 17, and 25
Week 9
|
0.40 Proportion of Participants
0.13
|
0.35 Proportion of Participants
0.12
|
—
|
|
Proportion of Participants With Progression-Free Survival (PFS) at Weeks 9, 17, and 25
Week 17
|
0.32 Proportion of Participants
0.13
|
0.14 Proportion of Participants
0.09
|
—
|
|
Proportion of Participants With Progression-Free Survival (PFS) at Weeks 9, 17, and 25
Week 25
|
0.21 Proportion of Participants
0.12
|
0.00 Proportion of Participants
0.00
|
—
|
SECONDARY outcome
Timeframe: Baseline to end of study drug therapy (up to 53.86 weeks)Population: Response-evaluable participants who achieved a complete response (CR) or partial response (PR)
Mean number of weeks of CR/PR (time from first date of CR/PR until first date PD observed. Tumor response defined per RECIST: CR: disappearance of all target/non-target lesions; PR: \>=30% decrease in sum of LDs of target lesions relative to baseline sum LD; PD: appearance of new lesion or \>=20% increase in sum of LD of target lesions relative to smallest sum LD or unequivocal progression of existing non-target lesions. Participants who died without reported PD were considered to have PD on date of death. For participants who neither progressed nor died, date of last tumor assessment used.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=2 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Mean Number of Weeks of Complete Response (CR) or Partial Response (PR)
|
31 weeks
Interval 8.14 to 53.86
|
—
|
—
|
SECONDARY outcome
Timeframe: At pre-dose and 1, 3, 6 and 12 hours after each dose administrationPopulation: Participants who were evaluable for pharmacokinetic analysis. "n" signifies the number of participants evaluable at each time point.
Mean plasma concentration was obtained directly from the concentration-time data.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=10 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=10 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
n=1 Participants
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Mean Plasma Concentration at Week 3
0 hour (n = 10, 10, 1)
|
9.02 nanograms (ng)/mL
Standard Deviation 3.79
|
7.14 nanograms (ng)/mL
Standard Deviation 4.41
|
2.88 nanograms (ng)/mL
Standard Deviation NA
Number of participants too small.
|
|
Mean Plasma Concentration at Week 3
1 hour (n = 10, 10, 1)
|
103.35 nanograms (ng)/mL
Standard Deviation 80.94
|
66.41 nanograms (ng)/mL
Standard Deviation 47.53
|
35.05 nanograms (ng)/mL
Standard Deviation NA
Number of participants too small.
|
|
Mean Plasma Concentration at Week 3
3 hour (n = 10, 10, 1)
|
50.98 nanograms (ng)/mL
Standard Deviation 35.23
|
35.47 nanograms (ng)/mL
Standard Deviation 21.51
|
32.58 nanograms (ng)/mL
Standard Deviation NA
Number of participants too small.
|
|
Mean Plasma Concentration at Week 3
6 hour (n = 10, 10, 1)
|
19.02 nanograms (ng)/mL
Standard Deviation 8.43
|
14.28 nanograms (ng)/mL
Standard Deviation 8.78
|
10.35 nanograms (ng)/mL
Standard Deviation NA
Number of participants too small.
|
|
Mean Plasma Concentration at Week 3
12 hour (n = 7, 6, 1)
|
9.11 nanograms (ng)/mL
Standard Deviation 3.39
|
15.43 nanograms (ng)/mL
Standard Deviation 17.60
|
3.60 nanograms (ng)/mL
Standard Deviation NA
Number of participants too small.
|
SECONDARY outcome
Timeframe: At pre-dose and 1, 3, 6 and 12 hours after each dose administrationPopulation: Participants who were evaluable for pharmacokinetic analysis. "n" signifies the number of participants evaluable at each time point.
Mean plasma concentration was obtained directly from the concentration-time data.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=10 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=10 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Mean Plasma Concentration at Week 7
6 hour (n = 2, 6)
|
15.75 nanograms (ng)/mL
Standard Deviation 0.14
|
14.25 nanograms (ng)/mL
Standard Deviation 4.69
|
—
|
|
Mean Plasma Concentration at Week 7
0 hour (n = 2, 6)
|
8.87 nanograms (ng)/mL
Standard Deviation 0.49
|
4.89 nanograms (ng)/mL
Standard Deviation 2.16
|
—
|
|
Mean Plasma Concentration at Week 7
1 hour (n = 2, 6)
|
120.92 nanograms (ng)/mL
Standard Deviation 23.16
|
84.36 nanograms (ng)/mL
Standard Deviation 62.01
|
—
|
|
Mean Plasma Concentration at Week 7
3 hour (n = 3, 6)
|
37.04 nanograms (ng)/mL
Standard Deviation 2.26
|
44.80 nanograms (ng)/mL
Standard Deviation 12.40
|
—
|
|
Mean Plasma Concentration at Week 7
12 hour (n = 1, 5)
|
8.39 nanograms (ng)/mL
Standard Deviation NA
Number of participants too small.
|
18.87 nanograms (ng)/mL
Standard Deviation 30.11
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 3 and Week 5Population: Participants who were evaluable for pharmacodynamic analysis.
Collagen Type IV is a measure of anti-angiogenic activity. Plasma samples for assessment of change in concentration of Collagen Type IV were obtained and analyzed by enzyme-linked immunosorbent assay.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=20 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Mean Change in Concentration of Collagen Type IV From Baseline
Week 3 (n = 17, 12)
|
39.51 percentage of baseline
Interval 28.6 to 51.34
|
26.92 percentage of baseline
Interval 12.06 to 43.76
|
—
|
|
Mean Change in Concentration of Collagen Type IV From Baseline
Week 5 (n = 8, 11)
|
34.31 percentage of baseline
Interval 17.46 to 53.58
|
35.18 percentage of baseline
Interval 15.8 to 57.82
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 3 and Week 5Population: Participants who were evaluable for pharmacodynamic analysis.
VEGFR2 is a measure of anti-angiogenic activity. Plasma samples for assessment of change in concentration of VEGFR2 were obtained and analyzed by enzyme-linked immunosorbent assay.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=20 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Mean Change in Concentration of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) From Baseline
Week 3 (n = 17, 12)
|
25.07 percentage of baseline
Interval 17.73 to 32.86
|
18.59 percentage of baseline
Interval 13.12 to 24.32
|
—
|
|
Mean Change in Concentration of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) From Baseline
Week 5 (n = 8, 11)
|
33.56 percentage of baseline
Interval 22.23 to 45.94
|
25.12 percentage of baseline
Interval 17.59 to 33.12
|
—
|
SECONDARY outcome
Timeframe: BaselinePopulation: All treated participants who were evaluable for the analysis. These data for tumor markers were integrated with those from other studies and are not reportable for this study alone.
Tumor markers are indicators of tumor activity which may be used to predict clinical benefit and circulating biomarkers may reveal key mechanisms of action. Tissue staining was performed for caveolin, phospho-caveolin, EphA2 and insulin-like growth factor binding protein 2 (IGFBP2) markers using immunohistochemistry assays.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: BaselinePopulation: All treated participants who were evaluable for the analysis. These data for pharmacogenomic analyses were integrated with those from other studies and are not reportable for this study alone.
Pharmacogenomic analysis included the assessment of the relationship between clinical benefit and mRNA expression levels and between clinical benefit and protein phosphorylation. Tumor mRNA expression was analyzed in all available tissues. mRNA was extracted from 96 formalin-fixed paraffin-embedded tissue (FFPET) samples, amplified, and fluorescently labeled. Gene expression profiling was conducted using Affymetrix Human Genome U133A 2.0 DNA microarrays. mRNA expression is reported as quantile normalized RMA values.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From start of study drug therapy up to 30 days after the last dose.Population: All treated participants.
An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). An SAE was defined as an AE that resulted in death, was life-threatening, required hospitalization (or prolongation of existing hospitalization), or was an important medical event.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=21 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs) or Adverse Events (AEs)
Death
|
1 participants
|
0 participants
|
—
|
|
Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs) or Adverse Events (AEs)
Serious adverse events (SAEs)
|
11 participants
|
3 participants
|
—
|
|
Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs) or Adverse Events (AEs)
All adverse events (AEs)
|
23 participants
|
21 participants
|
—
|
SECONDARY outcome
Timeframe: From start of study drug therapy up to 30 days after the last dose.Population: All treated participants
AE=any new untoward medical occurrence/worsening of pre-existing medical condition.SAE=AE that resulted in death, was life-threatening, required hospitalization (or prolongation of existing hospitalization), or was an important medical event. Drug-related SAEs or AEs are those events with relationship to study therapy of certain, probable or possible.AEs were graded using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), v3: Grade 1=mild, 2=moderate, 3=severe, 4=life threatening, 5=death.Participants who discontinued the study due to any drug-related AEs were also recorded.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=21 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Number of Participants Who Experienced Drug-related SAEs, Drug-related AEs, Drug-related Grade 3 AEs and Discontinuations Due to Drug-related AEs
Drug-related SAEs
|
5 participants
|
1 participants
|
—
|
|
Number of Participants Who Experienced Drug-related SAEs, Drug-related AEs, Drug-related Grade 3 AEs and Discontinuations Due to Drug-related AEs
Drug-related AEs
|
23 participants
|
19 participants
|
—
|
|
Number of Participants Who Experienced Drug-related SAEs, Drug-related AEs, Drug-related Grade 3 AEs and Discontinuations Due to Drug-related AEs
Drug-related Grade 3 AEs
|
12 participants
|
8 participants
|
—
|
|
Number of Participants Who Experienced Drug-related SAEs, Drug-related AEs, Drug-related Grade 3 AEs and Discontinuations Due to Drug-related AEs
Drug-related AEs Leading to Discontinuation
|
4 participants
|
6 participants
|
—
|
SECONDARY outcome
Timeframe: From start of study drug therapy up to 30 days after the last dose.Population: All treated participants
Most frequent drug-related AEs are those AEs with frequency \>=25% in either group. Drug-related AEs are those events with relationship to study therapy of certain, probable or possible.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=21 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Most Frequent Drug-related Adverse Events (AEs)
Dyspnea
|
10 participants
|
6 participants
|
—
|
|
Most Frequent Drug-related Adverse Events (AEs)
Pleural Effusion
|
9 participants
|
7 participants
|
—
|
|
Most Frequent Drug-related Adverse Events (AEs)
Diarrhea
|
12 participants
|
7 participants
|
—
|
|
Most Frequent Drug-related Adverse Events (AEs)
Fatigue
|
10 participants
|
14 participants
|
—
|
|
Most Frequent Drug-related Adverse Events (AEs)
Nausea
|
10 participants
|
14 participants
|
—
|
|
Most Frequent Drug-related Adverse Events (AEs)
Rash
|
9 participants
|
5 participants
|
—
|
|
Most Frequent Drug-related Adverse Events (AEs)
Headache
|
8 participants
|
4 participants
|
—
|
|
Most Frequent Drug-related Adverse Events (AEs)
Anorexia
|
9 participants
|
0 participants
|
—
|
|
Most Frequent Drug-related Adverse Events (AEs)
Vomiting
|
7 participants
|
6 participants
|
—
|
|
Most Frequent Drug-related Adverse Events (AEs)
Cough
|
7 participants
|
5 participants
|
—
|
|
Most Frequent Drug-related Adverse Events (AEs)
Abdominal pain
|
7 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Throughout study, from start of study drug therapy up to 30 days after the last dose.Population: All treated participants
Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening. Grades 3 and 4 criteria are defined as follows: Granulocytes: Grade 3 \<1.0 - 0.5 x 10\^9/L; Grade 4, \<0.5 x 10\^9/L. Hemoglobin: Grade 3, \<8.0 - 6.5 g/dL; Grade 4, \<6.5 g/dL. Platelets: Grade 3, \<50.0 - 25.0 x 10\^9/L; Grade 4, \<25.0 x 10\^9/L. Leukocytes: Grade 3, \<2.0 - 1.0 x 10\^9/L; Grade 4, \<1.0 x 10\^9/L.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=21 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements
Hemoglobin
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements
Leukocytes
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements
Platelet Count
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements
Granulocytes
|
3 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Throughout study, from start of study drug therapy up to 30 days after the last dose.Population: All treated participants
PT is a measure of the clotting ability of the blood. Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening and 5=death.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=21 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Number of Participants With Abnormalities (Grade 1 or 2) in Prothrombin Time (PT)
Grade 1
|
3 participants
|
0 participants
|
—
|
|
Number of Participants With Abnormalities (Grade 1 or 2) in Prothrombin Time (PT)
Grade 2
|
0 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Throughout study, from start of study drug therapy up to 30 days after the last dose.Population: All treated participants.
PTT is a measure of the clotting ability of the blood. Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening and 5=death.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=21 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Number of Participants With Abnormalities (Grade 1 or 2) in Partial Thromboplastin Time (PTT)
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Throughout study, from start of study drug therapy up to 30 days after the last dose.Population: All treated participants
Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening. Grade 3 and 4 criteria are defined as follows: ALT, AST and alkaline phosphatase: Grade 3: \>5-20 x upper limit of normal (ULN), Grade 4: \>20 x ULN.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=21 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase
Alkaline phosphatase
|
1 participants
|
1 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase
Alanine aminotransferase
|
1 participants
|
3 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase
Aspartate aminotransferase
|
0 participants
|
3 participants
|
—
|
SECONDARY outcome
Timeframe: Throughout study, from start of study drug therapy up to 30 days after the last dose.Population: All treated participants
Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening. Grade 3 and 4 criteria are defined as follows: Calcium: Grade 3-4 : \<6.0 - \<7.0 or \>12.5 - \>13.5 mg/dL, Potassium: Grade 3-4 : \<2.5 - \<3.0 or \>6.0 - \>7.0 mEq/L, Magnesium: Grade 3-4 : \<0.6 - \<0.8 or \>2.46 - \>6.6 mEq/L, Sodium:\< 120- 130 or \>155 - \>160 mEq/L.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=21 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium
High calcium
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium
Low calcium
|
0 participants
|
1 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium
High potassium
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium
Low potassium
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium
High magnesium
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium
Low magnesium
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium
High sodium
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium
Low sodium
|
0 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Throughout study, from start of study drug therapy up to 30 days after the last dose.Population: All treated participants
Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening. Grade 3 and 4 criteria are defined as follows: Creatinine: Grade 3-4 : \> 3.0 -6.0 ULN (upper limit of normal),Bicarbonate: Grade 3-4: \<16 -\<22 mEq/L, Phosphorous: Grade 3-4 : \<1.0 - \<2.0 mg/dL, Bilirubin, total: Grade 3-4: \>3.0 - \>10.0 ULN.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=21 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total).
Creatinine
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total).
Bicarbonate
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total).
Inorganic Phosphorus
|
1 participants
|
2 participants
|
—
|
|
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total).
Bilirubin, Total
|
0 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 3, 9, 17 and 25, then every 8 weeks until the end of study treatment (up to 17 weeks).Population: All treated participants
ECGs were performed and all recordings were evaluated by the investigator. Abnormalities, if present at any study time point, were listed. The following ECG variables were collected: heart rate, PR interval, QRS width, and QT interval. Abnormalities in ECGs were defined by reference to institutional reports.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=21 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Number of Participants With Identified Electrocardiogram (ECG) Abnormalities
|
4 participants
|
3 participants
|
—
|
SECONDARY outcome
Timeframe: At each study visit (Week 3, 5, 7, 9, 13, 17 and 25) and end of treatment (up to 17 weeks)Population: All treated participants
Vital signs included systolic and diastolic blood pressure and heart rate. The investigator used his or her judgement to decide whether or not the values were abnormal.
Outcome measures
| Measure |
Dasatinib 100 mg BID
n=23 Participants
Participants were administered an oral dose of 100 mg dasatinib tablet twice daily for a total daily dose (TDD) of 200 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 70 mg BID
n=21 Participants
Participants were administered an oral dose of 70 mg dasatinib tablet twice daily for a TDD of 140 mg. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
Dasatinib 50 mg BID
Participants were administered an oral dose of 50 mg dasatinib tablet twice daily for a total daily dose (TDD) of 100 mg. Study treatment continued for as long as it was tolerated, or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|---|---|
|
Number of Participants With Abnormal Vital Signs Measurements
|
0 participants
|
0 participants
|
—
|
Adverse Events
All Participants
Serious events: 14 serious events
Other events: 44 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Participants
n=44 participants at risk
All treated participants who were administered a twice-daily oral dose of either 100 mg (TDD 200 mg) or 70 mg (TDD 140 mg) dasatinib tablet. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|
|
Cardiac disorders
MYOPERICARDITIS
|
2.3%
1/44
|
|
Cardiac disorders
PERICARDIAL EFFUSION
|
4.5%
2/44
|
|
Vascular disorders
HYPOTENSION
|
4.5%
2/44
|
|
Gastrointestinal disorders
NAUSEA
|
2.3%
1/44
|
|
Gastrointestinal disorders
ASCITES
|
2.3%
1/44
|
|
Gastrointestinal disorders
VOMITING
|
4.5%
2/44
|
|
Gastrointestinal disorders
DYSPHAGIA
|
2.3%
1/44
|
|
Gastrointestinal disorders
CONSTIPATION
|
2.3%
1/44
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
2.3%
1/44
|
|
Infections and infestations
INFECTION
|
2.3%
1/44
|
|
Infections and infestations
PNEUMONIA
|
2.3%
1/44
|
|
Renal and urinary disorders
RENAL FAILURE ACUTE
|
2.3%
1/44
|
|
Skin and subcutaneous tissue disorders
PERIORBITAL OEDEMA
|
2.3%
1/44
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
2.3%
1/44
|
|
Musculoskeletal and connective tissue disorders
COSTOCHONDRITIS
|
2.3%
1/44
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
2.3%
1/44
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
6.8%
3/44
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS
|
2.3%
1/44
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONITIS
|
2.3%
1/44
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
6.8%
3/44
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
2.3%
1/44
|
|
General disorders
PYREXIA
|
4.5%
2/44
|
|
General disorders
GENERALISED OEDEMA
|
2.3%
1/44
|
|
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION
|
2.3%
1/44
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT NEOPLASM PROGRESSION
|
4.5%
2/44
|
Other adverse events
| Measure |
All Participants
n=44 participants at risk
All treated participants who were administered a twice-daily oral dose of either 100 mg (TDD 200 mg) or 70 mg (TDD 140 mg) dasatinib tablet. Study treatment continued for as long as it was tolerated, or until PD, defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
|
|---|---|
|
Eye disorders
DRY EYE
|
6.8%
3/44
|
|
Investigations
WEIGHT DECREASED
|
11.4%
5/44
|
|
Investigations
ALANINE AMINOTRANSFERASE
|
9.1%
4/44
|
|
Investigations
ASPARTATE AMINOTRANSFERASE
|
9.1%
4/44
|
|
Investigations
ELECTROCARDIOGRAM QT PROLONGED
|
6.8%
3/44
|
|
Vascular disorders
FLUSHING
|
9.1%
4/44
|
|
Vascular disorders
HOT FLUSH
|
11.4%
5/44
|
|
Psychiatric disorders
ANXIETY
|
11.4%
5/44
|
|
Psychiatric disorders
INSOMNIA
|
15.9%
7/44
|
|
Nervous system disorders
HEADACHE
|
34.1%
15/44
|
|
Nervous system disorders
DIZZINESS
|
6.8%
3/44
|
|
Nervous system disorders
PARAESTHESIA
|
6.8%
3/44
|
|
Gastrointestinal disorders
NAUSEA
|
56.8%
25/44
|
|
Gastrointestinal disorders
VOMITING
|
31.8%
14/44
|
|
Gastrointestinal disorders
DIARRHOEA
|
45.5%
20/44
|
|
Gastrointestinal disorders
DYSPEPSIA
|
6.8%
3/44
|
|
Gastrointestinal disorders
STOMATITIS
|
9.1%
4/44
|
|
Gastrointestinal disorders
CONSTIPATION
|
22.7%
10/44
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
18.2%
8/44
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
9.1%
4/44
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
6.8%
3/44
|
|
Infections and infestations
URINARY TRACT INFECTION
|
6.8%
3/44
|
|
Metabolism and nutrition disorders
ANOREXIA
|
27.3%
12/44
|
|
Blood and lymphatic system disorders
ANAEMIA
|
9.1%
4/44
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
9.1%
4/44
|
|
Skin and subcutaneous tissue disorders
RASH
|
36.4%
16/44
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
6.8%
3/44
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
9.1%
4/44
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
18.2%
8/44
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
13.6%
6/44
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
13.6%
6/44
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
11.4%
5/44
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
9.1%
4/44
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
6.8%
3/44
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
38.6%
17/44
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
43.2%
19/44
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
34.1%
15/44
|
|
General disorders
PAIN
|
6.8%
3/44
|
|
General disorders
FATIGUE
|
56.8%
25/44
|
|
General disorders
PYREXIA
|
15.9%
7/44
|
|
General disorders
ASTHENIA
|
18.2%
8/44
|
|
General disorders
CHEST PAIN
|
6.8%
3/44
|
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