A Study of Dasatinib (BMS-354825) in Patients With Advanced 'Triple-negative' Breast Cancer

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00371254
• Collaborator: (none)
• Enrollment: 55
• Locations: 10
• Arms: 2
• Duration (Months): 21
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will determine whether the investigational drug dasatinib is effective in treatment of women with progressive advanced triple-negative breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Metastasis	Drug: Dasatinib; Drug: Dasatinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Dasatinib (BMS-354825) for Advanced 'Triple-negative' Breast Cancer
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Dasatinib; Tablets, Oral, 100 mg, twice daily as long as the patient benefits (avg <6 months); Other Names: Sprycel BMS-354825
Experimental: 2	Drug: Dasatinib; Tablets, Oral, 70 mg, twice daily as long as the patient benefits (avg <6 months)

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Complete Response (CR) or Partial Response (PR) [Baseline to end of study drug therapy (up to 65 weeks).]

   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.

2. Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Baseline to end of study drug therapy (up to 65 weeks).]

   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.

Secondary Outcome Measures

1. Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study [Baseline to 16 weeks.]

   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.

2. Percentage of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study [Baseline to 16 weeks]

   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.

3. Proportion of Participants With Progression-Free Survival (PFS) at Weeks 9, 17, and 25 [Weeks 9, 17, and 25]

   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.

4. Mean Number of Weeks of Complete Response (CR) or Partial Response (PR) [Baseline to end of study drug therapy (up to 53.86 weeks)]

   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.

5. Mean Plasma Concentration at Week 3 [At pre-dose and 1, 3, 6 and 12 hours after each dose administration]

   Mean plasma concentration was obtained directly from the concentration-time data.

6. Mean Plasma Concentration at Week 7 [At pre-dose and 1, 3, 6 and 12 hours after each dose administration]

   Mean plasma concentration was obtained directly from the concentration-time data.

7. Mean Change in Concentration of Collagen Type IV From Baseline [Baseline, Week 3 and Week 5]

   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.

8. Mean Change in Concentration of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) From Baseline [Baseline, Week 3 and Week 5]

   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.

9. Percentage Change in Tumor Biomarkers [Baseline]

   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.

10. Profiling of Messenger-ribonucleic Acid (mRNA) Expression: mRNA Signal Intensity [Baseline]

    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.

11. Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs) or Adverse Events (AEs) [From start of study drug therapy up to 30 days after the last dose.]

    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.

12. Number of Participants Who Experienced Drug-related SAEs, Drug-related AEs, Drug-related Grade 3 AEs and Discontinuations Due to Drug-related AEs [From start of study drug therapy up to 30 days after the last dose.]

    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.

13. Most Frequent Drug-related Adverse Events (AEs) [From start of study drug therapy up to 30 days after the last dose.]

    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.

14. Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements [Throughout study, from start of study drug therapy up to 30 days after the last dose.]

    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.

15. Number of Participants With Abnormalities (Grade 1 or 2) in Prothrombin Time (PT) [Throughout study, from start of study drug therapy up to 30 days after the last dose.]

    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.

16. Number of Participants With Abnormalities (Grade 1 or 2) in Partial Thromboplastin Time (PTT) [Throughout study, from start of study drug therapy up to 30 days after the last dose.]

    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.

17. Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase [Throughout study, from start of study drug therapy up to 30 days after the last dose.]

    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.

18. Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium [Throughout study, from start of study drug therapy up to 30 days after the last dose.]

    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.

19. Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total). [Throughout study, from start of study drug therapy up to 30 days after the last dose.]

    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.

20. Number of Participants With Identified Electrocardiogram (ECG) Abnormalities [Baseline, Weeks 3, 9, 17 and 25, then every 8 weeks until the end of study treatment (up to 17 weeks).]

    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.

21. Number of Participants With Abnormal Vital Signs Measurements [At each study visit (Week 3, 5, 7, 9, 13, 17 and 25) and end of treatment (up to 17 weeks)]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• females, 18 or older

• recurrent or progressive locally advanced, or 'triple negative' metastatic breast cancer

• paraffin-embedded tissue block must be available

• measurable disease

• prior chemotherapy with an anthracycline, a taxane, or both (neoadjuvant, adjuvant, or metastatic setting)

• 0, 1 or 2 chemotherapies in the metastatic setting

• adequate organ function

Exclusion Criteria:

• Metastatic disease confined to bone only

• Symptomatic CNS metastasis

• Concurrent medical condition which may increase the risk of toxicity

• Unable to take oral medication

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ucsf-Comprehensive Cancer Center	San Francisco	California	United States	94143
2	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32224
3	Dana-Farber Cancer Inst	Boston	Massachusetts	United States	02115
4	Montefiore Medical Center	Bronx	New York	United States	10461
5	University Of Texas Md Anderson Cancer Ctr	Houston	Texas	United States	77030
6	Local Institution	Paris		France	75231
7	Local Institution	Toulouse Cedex 3		France	31052
8	Local Institution	Modena		Italy	41100
9	Local Institution	Barcelona		Spain	08035
10	Local Institution	Lleida		Spain	25198

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00371254
• Other Study ID Numbers: CA180-059
• First Posted: Sep 4, 2006
• Last Update Posted: Mar 15, 2011
• Last Verified: Feb 1, 2011

• Keywords provided by , ,: Recurrent, locally-advanced, or 'triple negative' metastatic breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms; Dasatinib

Study Results

Participant Flow

Pre-assignment Detail	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)

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	23	21
COMPLETED	0	0
NOT COMPLETED	23	21

Baseline Characteristics

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	23	21	44
Age, Customized (participants) [Number]
<50 years	4 17.4%	9 42.9%	13 29.5%
>=50 years	19 82.6%	12 57.1%	31 70.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.4 (8.98)	51.5 (9.34)	54.0 (9.38)
Sex: Female, Male (Count of Participants)
Female	23 100%	21 100%	44 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 13%	2 9.5%	5 11.4%
Not Hispanic or Latino	9 39.1%	12 57.1%	21 47.7%
Unknown or Not Reported	11 47.8%	7 33.3%	18 40.9%
Race/Ethnicity, Customized (participants) [Number]
White	20 87%	19 90.5%	39 88.6%
Black or African American	2 8.7%	1 4.8%	3 6.8%
Asian	0 0%	1 4.8%	1 2.3%
Unknown or Not Reported	1 4.3%	0 0%	1 2.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Complete Response (CR) or Partial Response (PR)
Description	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.
Time Frame	Baseline to end of study drug therapy (up to 65 weeks).

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	20
Number [participants]	2 8.7%	0 0%

2. Secondary Outcome

Title	Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study
Description	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.
Time Frame	Baseline to 16 weeks.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	20
Number [Participants]	3 13%	1 4.8%

3. Secondary Outcome

Title	Percentage of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study
Description	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.
Time Frame	Baseline to 16 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	20
Number (95% Confidence Interval) [percentage of participants]	13.04 56.7%	5.0 23.8%

4. Secondary Outcome

Title	Proportion of Participants With Progression-Free Survival (PFS) at Weeks 9, 17, and 25
Description	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.
Time Frame	Weeks 9, 17, and 25

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	21
Week 9	0.40 (0.13) 1.7%	0.35 (0.12) 1.7%
Week 17	0.32 (0.13) 1.4%	0.14 (0.09) 0.7%
Week 25	0.21 (0.12) 0.9%	0.00 (0.00) 0%

5. Secondary Outcome

Title	Mean Number of Weeks of Complete Response (CR) or Partial Response (PR)
Description	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.
Time Frame	Baseline to end of study drug therapy (up to 53.86 weeks)

Outcome Measure Data

Analysis Population Description

Response-evaluable participants who achieved a complete response (CR) or partial response (PR)

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	2	0
Mean (Full Range) [weeks]	31

6. Secondary Outcome

Title	Mean Plasma Concentration at Week 3
Description	Mean plasma concentration was obtained directly from the concentration-time data.
Time Frame	At pre-dose and 1, 3, 6 and 12 hours after each dose administration

Outcome Measure Data

Analysis Population Description

Participants who were evaluable for pharmacokinetic analysis. "n" signifies the number of participants evaluable at each time point.

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID	Dasatinib 50 mg BID
Arm/Group Description	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.	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.	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.
Measure Participants	10	10	1
0 hour (n = 10, 10, 1)	9.02 (3.79)	7.14 (4.41)	2.88 (NA)
1 hour (n = 10, 10, 1)	103.35 (80.94)	66.41 (47.53)	35.05 (NA)
3 hour (n = 10, 10, 1)	50.98 (35.23)	35.47 (21.51)	32.58 (NA)
6 hour (n = 10, 10, 1)	19.02 (8.43)	14.28 (8.78)	10.35 (NA)
12 hour (n = 7, 6, 1)	9.11 (3.39)	15.43 (17.60)	3.60 (NA)

7. Primary Outcome

Title	Percentage of Participants With Complete Response (CR) or Partial Response (PR)
Description	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.
Time Frame	Baseline to end of study drug therapy (up to 65 weeks).

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	20
Number (95% Confidence Interval) [percentage of participants]	8.7 37.8%	0.0 0%

8. Secondary Outcome

Title	Mean Plasma Concentration at Week 7
Description	Mean plasma concentration was obtained directly from the concentration-time data.
Time Frame	At pre-dose and 1, 3, 6 and 12 hours after each dose administration

Outcome Measure Data

Analysis Population Description

Participants who were evaluable for pharmacokinetic analysis. "n" signifies the number of participants evaluable at each time point.

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	10	10
0 hour (n = 2, 6)	8.87 (0.49)	4.89 (2.16)
1 hour (n = 2, 6)	120.92 (23.16)	84.36 (62.01)
3 hour (n = 3, 6)	37.04 (2.26)	44.80 (12.40)
6 hour (n = 2, 6)	15.75 (0.14)	14.25 (4.69)
12 hour (n = 1, 5)	8.39 (NA)	18.87 (30.11)

9. Secondary Outcome

Title	Mean Change in Concentration of Collagen Type IV From Baseline
Description	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.
Time Frame	Baseline, Week 3 and Week 5

Outcome Measure Data

Analysis Population Description

Participants who were evaluable for pharmacodynamic analysis.

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	20
Week 3 (n = 17, 12)	39.51	26.92
Week 5 (n = 8, 11)	34.31	35.18

10. Secondary Outcome

Title	Mean Change in Concentration of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) From Baseline
Description	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.
Time Frame	Baseline, Week 3 and Week 5

Outcome Measure Data

Analysis Population Description

Participants who were evaluable for pharmacodynamic analysis.

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	20
Week 3 (n = 17, 12)	25.07	18.59
Week 5 (n = 8, 11)	33.56	25.12

11. Secondary Outcome

Title	Percentage Change in Tumor Biomarkers
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	0	0

12. Secondary Outcome

Title	Profiling of Messenger-ribonucleic Acid (mRNA) Expression: mRNA Signal Intensity
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	0	0

13. Secondary Outcome

Title	Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs) or Adverse Events (AEs)
Description	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.
Time Frame	From start of study drug therapy up to 30 days after the last dose.

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	21
Death	1 4.3%	0 0%
Serious adverse events (SAEs)	11 47.8%	3 14.3%
All adverse events (AEs)	23 100%	21 100%

14. Secondary Outcome

Title	Number of Participants Who Experienced Drug-related SAEs, Drug-related AEs, Drug-related Grade 3 AEs and Discontinuations Due to Drug-related AEs
Description	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.
Time Frame	From start of study drug therapy up to 30 days after the last dose.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	21
Drug-related SAEs	5 21.7%	1 4.8%
Drug-related AEs	23 100%	19 90.5%
Drug-related Grade 3 AEs	12 52.2%	8 38.1%
Drug-related AEs Leading to Discontinuation	4 17.4%	6 28.6%

15. Secondary Outcome

Title	Most Frequent Drug-related Adverse Events (AEs)
Description	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.
Time Frame	From start of study drug therapy up to 30 days after the last dose.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	21
Diarrhea	12 52.2%	7 33.3%
Fatigue	10 43.5%	14 66.7%
Nausea	10 43.5%	14 66.7%
Dyspnea	10 43.5%	6 28.6%
Pleural Effusion	9 39.1%	7 33.3%
Rash	9 39.1%	5 23.8%
Headache	8 34.8%	4 19%
Anorexia	9 39.1%	0 0%
Vomiting	7 30.4%	6 28.6%
Cough	7 30.4%	5 23.8%
Abdominal pain	7 30.4%	0 0%

16. Secondary Outcome

Title	Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements
Description	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.
Time Frame	Throughout study, from start of study drug therapy up to 30 days after the last dose.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	21
Granulocytes	3 13%	0 0%
Hemoglobin	0 0%	0 0%
Platelet Count	0 0%	0 0%
Leukocytes	0 0%	0 0%

17. Secondary Outcome

Title	Number of Participants With Abnormalities (Grade 1 or 2) in Prothrombin Time (PT)
Description	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.
Time Frame	Throughout study, from start of study drug therapy up to 30 days after the last dose.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	21
Grade 1	3 13%	0 0%
Grade 2	0 0%	0 0%

18. Secondary Outcome

Title	Number of Participants With Abnormalities (Grade 1 or 2) in Partial Thromboplastin Time (PTT)
Description	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.
Time Frame	Throughout study, from start of study drug therapy up to 30 days after the last dose.

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	21
Number [Participants]	0 0%	0 0%

19. Secondary Outcome

Title	Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase
Description	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.
Time Frame	Throughout study, from start of study drug therapy up to 30 days after the last dose.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	21
Alkaline phosphatase	1 4.3%	1 4.8%
Alanine aminotransferase	1 4.3%	3 14.3%
Aspartate aminotransferase	0 0%	3 14.3%

20. Secondary Outcome

Title	Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium
Description	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.
Time Frame	Throughout study, from start of study drug therapy up to 30 days after the last dose.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	21
High calcium	0 0%	0 0%
Low calcium	0 0%	1 4.8%
High potassium	0 0%	0 0%
Low potassium	1 4.3%	0 0%
High magnesium	0 0%	0 0%
Low magnesium	0 0%	0 0%
High sodium	0 0%	0 0%
Low sodium	0 0%	0 0%

21. Secondary Outcome

Title	Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total).
Description	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.
Time Frame	Throughout study, from start of study drug therapy up to 30 days after the last dose.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	21
Creatinine	0 0%	0 0%
Bicarbonate	0 0%	0 0%
Inorganic Phosphorus	1 4.3%	2 9.5%
Bilirubin, Total	0 0%	0 0%

22. Secondary Outcome

Title	Number of Participants With Identified Electrocardiogram (ECG) Abnormalities
Description	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.
Time Frame	Baseline, Weeks 3, 9, 17 and 25, then every 8 weeks until the end of study treatment (up to 17 weeks).

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	21
Number [participants]	4 17.4%	3 14.3%

23. Secondary Outcome

Title	Number of Participants With Abnormal Vital Signs Measurements
Description	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.
Time Frame	At each study visit (Week 3, 5, 7, 9, 13, 17 and 25) and end of treatment (up to 17 weeks)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Dasatinib 100 mg BID	Dasatinib 70 mg BID
Arm/Group Description	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.	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.
Measure Participants	23	21
Number [participants]	0 0%	0 0%

Adverse Events

Arm/Group Title	All Participants
Arm/Group Description	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.
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	14/44 (31.8%)
Cardiac disorders
MYOPERICARDITIS	1/44 (2.3%)
PERICARDIAL EFFUSION	2/44 (4.5%)
Gastrointestinal disorders
NAUSEA	1/44 (2.3%)
ASCITES	1/44 (2.3%)
VOMITING	2/44 (4.5%)
DYSPHAGIA	1/44 (2.3%)
CONSTIPATION	1/44 (2.3%)
ABDOMINAL PAIN	1/44 (2.3%)
General disorders
PYREXIA	2/44 (4.5%)
GENERALISED OEDEMA	1/44 (2.3%)
GENERAL PHYSICAL HEALTH DETERIORATION	1/44 (2.3%)
Infections and infestations
INFECTION	1/44 (2.3%)
PNEUMONIA	1/44 (2.3%)
Musculoskeletal and connective tissue disorders
BACK PAIN	1/44 (2.3%)
COSTOCHONDRITIS	1/44 (2.3%)
MUSCULOSKELETAL CHEST PAIN	1/44 (2.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT NEOPLASM PROGRESSION	2/44 (4.5%)
Renal and urinary disorders
RENAL FAILURE ACUTE	1/44 (2.3%)
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	3/44 (6.8%)
HAEMOPTYSIS	1/44 (2.3%)
PNEUMONITIS	1/44 (2.3%)
PLEURAL EFFUSION	3/44 (6.8%)
RESPIRATORY FAILURE	1/44 (2.3%)
Skin and subcutaneous tissue disorders
PERIORBITAL OEDEMA	1/44 (2.3%)
Vascular disorders
HYPOTENSION	2/44 (4.5%)
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	44/44 (100%)
Blood and lymphatic system disorders
ANAEMIA	4/44 (9.1%)
NEUTROPENIA	4/44 (9.1%)
Eye disorders
DRY EYE	3/44 (6.8%)
Gastrointestinal disorders
NAUSEA	25/44 (56.8%)
VOMITING	14/44 (31.8%)
DIARRHOEA	20/44 (45.5%)
DYSPEPSIA	3/44 (6.8%)
STOMATITIS	4/44 (9.1%)
CONSTIPATION	10/44 (22.7%)
ABDOMINAL PAIN	8/44 (18.2%)
ABDOMINAL DISTENSION	4/44 (9.1%)
ABDOMINAL PAIN UPPER	3/44 (6.8%)
General disorders
PAIN	3/44 (6.8%)
FATIGUE	25/44 (56.8%)
PYREXIA	7/44 (15.9%)
ASTHENIA	8/44 (18.2%)
CHEST PAIN	3/44 (6.8%)
Infections and infestations
URINARY TRACT INFECTION	3/44 (6.8%)
Investigations
WEIGHT DECREASED	5/44 (11.4%)
ALANINE AMINOTRANSFERASE	4/44 (9.1%)
ASPARTATE AMINOTRANSFERASE	4/44 (9.1%)
ELECTROCARDIOGRAM QT PROLONGED	3/44 (6.8%)
Metabolism and nutrition disorders
ANOREXIA	12/44 (27.3%)
Musculoskeletal and connective tissue disorders
MYALGIA	8/44 (18.2%)
BACK PAIN	6/44 (13.6%)
ARTHRALGIA	6/44 (13.6%)
PAIN IN EXTREMITY	5/44 (11.4%)
MUSCULOSKELETAL PAIN	4/44 (9.1%)
MUSCULOSKELETAL CHEST PAIN	3/44 (6.8%)
Nervous system disorders
HEADACHE	15/44 (34.1%)
DIZZINESS	3/44 (6.8%)
PARAESTHESIA	3/44 (6.8%)
Psychiatric disorders
ANXIETY	5/44 (11.4%)
INSOMNIA	7/44 (15.9%)
Respiratory, thoracic and mediastinal disorders
COUGH	17/44 (38.6%)
DYSPNOEA	19/44 (43.2%)
PLEURAL EFFUSION	15/44 (34.1%)
Skin and subcutaneous tissue disorders
RASH	16/44 (36.4%)
ERYTHEMA	3/44 (6.8%)
PRURITUS	4/44 (9.1%)
Vascular disorders
FLUSHING	4/44 (9.1%)
HOT FLUSH	5/44 (11.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.