Breast Cancer, Metastasis
Conditions
Keywords
Recurrent, locally-advanced, or 'triple negative' metastatic breast cancer
Brief summary
This study will determine whether the investigational drug dasatinib is effective in treatment of women with progressive advanced triple-negative breast cancer.
Interventions
DRUGDasatinib
Tablets, Oral, 100 mg, twice daily as long as the patient benefits (avg \<6 months)
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* females, 18 or older * recurrent 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
France, Italy, Spain, United States
Participant flow
Pre-assignment details
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)
Participants by arm
| Arm | Count |
|---|---|
| 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. | 23 |
| 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. | 21 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse event unrelated to study drug | 0 | 1 |
| Overall Study | Disease progression | 13 | 13 |
| Overall Study | Investigator Decision | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Study drug toxicity | 3 | 5 |
| Overall Study | Subject request | 5 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Dasatinib 70 mg BID | Dasatinib 100 mg BID |
|---|---|---|---|
| Age Continuous | 54.0 years STANDARD_DEVIATION 9.38 | 51.5 years STANDARD_DEVIATION 9.34 | 56.4 years STANDARD_DEVIATION 8.98 |
| Age, Customized <50 years | 13 participants | 9 participants | 4 participants |
| Age, Customized >=50 years | 31 participants | 12 participants | 19 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 12 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 18 Participants | 7 Participants | 11 Participants |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 3 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 39 participants | 19 participants | 20 participants |
| Sex: Female, Male Female | 44 Participants | 21 Participants | 23 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 44 / 44 |
| serious Total, serious adverse events | 14 / 44 |
Outcome results
Primary
Number of Participants With Complete Response (CR) or Partial Response (PR)
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).
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib 100 mg BID | Number of Participants With Complete Response (CR) or Partial Response (PR) | 2 participants |
| Dasatinib 70 mg BID | Number of Participants With Complete Response (CR) or Partial Response (PR) | 0 participants |
Primary
Percentage of Participants With Complete Response (CR) or Partial Response (PR)
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).
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib 100 mg BID | Percentage of Participants With Complete Response (CR) or Partial Response (PR) | 8.7 percentage of participants |
| Dasatinib 70 mg BID | Percentage of Participants With Complete Response (CR) or Partial Response (PR) | 0.0 percentage of participants |
Secondary
Mean Change in Concentration of Collagen Type IV From Baseline
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
Population: Participants who were evaluable for pharmacodynamic analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Dasatinib 100 mg BID | Mean Change in Concentration of Collagen Type IV From Baseline | Week 3 (n = 17, 12) | 39.51 percentage of baseline |
| Dasatinib 100 mg BID | Mean Change in Concentration of Collagen Type IV From Baseline | Week 5 (n = 8, 11) | 34.31 percentage of baseline |
| Dasatinib 70 mg BID | Mean Change in Concentration of Collagen Type IV From Baseline | Week 3 (n = 17, 12) | 26.92 percentage of baseline |
| Dasatinib 70 mg BID | Mean Change in Concentration of Collagen Type IV From Baseline | Week 5 (n = 8, 11) | 35.18 percentage of baseline |
Secondary
Mean Change in Concentration of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) From Baseline
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
Population: Participants who were evaluable for pharmacodynamic analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Dasatinib 100 mg BID | Mean Change in Concentration of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) From Baseline | Week 3 (n = 17, 12) | 25.07 percentage of baseline |
| Dasatinib 100 mg BID | Mean Change in Concentration of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) From Baseline | Week 5 (n = 8, 11) | 33.56 percentage of baseline |
| Dasatinib 70 mg BID | Mean Change in Concentration of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) From Baseline | Week 3 (n = 17, 12) | 18.59 percentage of baseline |
| Dasatinib 70 mg BID | Mean Change in Concentration of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) From Baseline | Week 5 (n = 8, 11) | 25.12 percentage of baseline |
Secondary
Mean Number of Weeks of 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.
Time frame: 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)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dasatinib 100 mg BID | Mean Number of Weeks of Complete Response (CR) or Partial Response (PR) | 31 weeks |
Secondary
Mean Plasma Concentration at Week 3
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
Population: Participants who were evaluable for pharmacokinetic analysis. n signifies the number of participants evaluable at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dasatinib 100 mg BID | Mean Plasma Concentration at Week 3 | 6 hour (n = 10, 10, 1) | 19.02 nanograms (ng)/mL | Standard Deviation 8.43 |
| Dasatinib 100 mg BID | Mean Plasma Concentration at Week 3 | 0 hour (n = 10, 10, 1) | 9.02 nanograms (ng)/mL | Standard Deviation 3.79 |
| Dasatinib 100 mg BID | Mean Plasma Concentration at Week 3 | 1 hour (n = 10, 10, 1) | 103.35 nanograms (ng)/mL | Standard Deviation 80.94 |
| Dasatinib 100 mg BID | Mean Plasma Concentration at Week 3 | 3 hour (n = 10, 10, 1) | 50.98 nanograms (ng)/mL | Standard Deviation 35.23 |
| Dasatinib 100 mg BID | Mean Plasma Concentration at Week 3 | 12 hour (n = 7, 6, 1) | 9.11 nanograms (ng)/mL | Standard Deviation 3.39 |
| Dasatinib 70 mg BID | Mean Plasma Concentration at Week 3 | 1 hour (n = 10, 10, 1) | 66.41 nanograms (ng)/mL | Standard Deviation 47.53 |
| Dasatinib 70 mg BID | Mean Plasma Concentration at Week 3 | 12 hour (n = 7, 6, 1) | 15.43 nanograms (ng)/mL | Standard Deviation 17.6 |
| Dasatinib 70 mg BID | Mean Plasma Concentration at Week 3 | 3 hour (n = 10, 10, 1) | 35.47 nanograms (ng)/mL | Standard Deviation 21.51 |
| Dasatinib 70 mg BID | Mean Plasma Concentration at Week 3 | 6 hour (n = 10, 10, 1) | 14.28 nanograms (ng)/mL | Standard Deviation 8.78 |
| Dasatinib 70 mg BID | Mean Plasma Concentration at Week 3 | 0 hour (n = 10, 10, 1) | 7.14 nanograms (ng)/mL | Standard Deviation 4.41 |
| Dasatinib 50 mg BID | Mean Plasma Concentration at Week 3 | 0 hour (n = 10, 10, 1) | 2.88 nanograms (ng)/mL | — |
| Dasatinib 50 mg BID | Mean Plasma Concentration at Week 3 | 1 hour (n = 10, 10, 1) | 35.05 nanograms (ng)/mL | — |
| Dasatinib 50 mg BID | Mean Plasma Concentration at Week 3 | 6 hour (n = 10, 10, 1) | 10.35 nanograms (ng)/mL | — |
| Dasatinib 50 mg BID | Mean Plasma Concentration at Week 3 | 12 hour (n = 7, 6, 1) | 3.60 nanograms (ng)/mL | — |
| Dasatinib 50 mg BID | Mean Plasma Concentration at Week 3 | 3 hour (n = 10, 10, 1) | 32.58 nanograms (ng)/mL | — |
Secondary
Mean Plasma Concentration at Week 7
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
Population: Participants who were evaluable for pharmacokinetic analysis. n signifies the number of participants evaluable at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dasatinib 100 mg BID | Mean Plasma Concentration at Week 7 | 1 hour (n = 2, 6) | 120.92 nanograms (ng)/mL | Standard Deviation 23.16 |
| Dasatinib 100 mg BID | Mean Plasma Concentration at Week 7 | 6 hour (n = 2, 6) | 15.75 nanograms (ng)/mL | Standard Deviation 0.14 |
| Dasatinib 100 mg BID | Mean Plasma Concentration at Week 7 | 3 hour (n = 3, 6) | 37.04 nanograms (ng)/mL | Standard Deviation 2.26 |
| Dasatinib 100 mg BID | Mean Plasma Concentration at Week 7 | 12 hour (n = 1, 5) | 8.39 nanograms (ng)/mL | — |
| Dasatinib 100 mg BID | Mean Plasma Concentration at Week 7 | 0 hour (n = 2, 6) | 8.87 nanograms (ng)/mL | Standard Deviation 0.49 |
| Dasatinib 70 mg BID | Mean Plasma Concentration at Week 7 | 12 hour (n = 1, 5) | 18.87 nanograms (ng)/mL | Standard Deviation 30.11 |
| Dasatinib 70 mg BID | Mean Plasma Concentration at Week 7 | 0 hour (n = 2, 6) | 4.89 nanograms (ng)/mL | Standard Deviation 2.16 |
| Dasatinib 70 mg BID | Mean Plasma Concentration at Week 7 | 1 hour (n = 2, 6) | 84.36 nanograms (ng)/mL | Standard Deviation 62.01 |
| Dasatinib 70 mg BID | Mean Plasma Concentration at Week 7 | 3 hour (n = 3, 6) | 44.80 nanograms (ng)/mL | Standard Deviation 12.4 |
| Dasatinib 70 mg BID | Mean Plasma Concentration at Week 7 | 6 hour (n = 2, 6) | 14.25 nanograms (ng)/mL | Standard Deviation 4.69 |
Secondary
Most Frequent Drug-related Adverse Events (AEs)
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.
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib 100 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Dyspnea | 10 participants |
| Dasatinib 100 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Headache | 8 participants |
| Dasatinib 100 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Nausea | 10 participants |
| Dasatinib 100 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Anorexia | 9 participants |
| Dasatinib 100 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Pleural Effusion | 9 participants |
| Dasatinib 100 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Vomiting | 7 participants |
| Dasatinib 100 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Fatigue | 10 participants |
| Dasatinib 100 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Cough | 7 participants |
| Dasatinib 100 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Rash | 9 participants |
| Dasatinib 100 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Abdominal pain | 7 participants |
| Dasatinib 100 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Diarrhea | 12 participants |
| Dasatinib 70 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Abdominal pain | 0 participants |
| Dasatinib 70 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Diarrhea | 7 participants |
| Dasatinib 70 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Fatigue | 14 participants |
| Dasatinib 70 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Nausea | 14 participants |
| Dasatinib 70 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Dyspnea | 6 participants |
| Dasatinib 70 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Pleural Effusion | 7 participants |
| Dasatinib 70 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Rash | 5 participants |
| Dasatinib 70 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Headache | 4 participants |
| Dasatinib 70 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Anorexia | 0 participants |
| Dasatinib 70 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Vomiting | 6 participants |
| Dasatinib 70 mg BID | Most Frequent Drug-related Adverse Events (AEs) | Cough | 5 participants |
Secondary
Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs) or Adverse Events (AEs)
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.
Population: All treated participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib 100 mg BID | Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs) or Adverse Events (AEs) | Death | 1 participants |
| Dasatinib 100 mg BID | Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs) or Adverse Events (AEs) | Serious adverse events (SAEs) | 11 participants |
| Dasatinib 100 mg BID | Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs) or Adverse Events (AEs) | All adverse events (AEs) | 23 participants |
| Dasatinib 70 mg BID | Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs) or Adverse Events (AEs) | Death | 0 participants |
| Dasatinib 70 mg BID | Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs) or Adverse Events (AEs) | Serious adverse events (SAEs) | 3 participants |
| Dasatinib 70 mg BID | Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs) or Adverse Events (AEs) | All adverse events (AEs) | 21 participants |
Secondary
Number of Participants Who Experienced Drug-related SAEs, Drug-related AEs, Drug-related Grade 3 AEs and Discontinuations Due to Drug-related AEs
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.
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib 100 mg BID | 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 |
| Dasatinib 100 mg BID | 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 |
| Dasatinib 100 mg BID | 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 |
| Dasatinib 100 mg BID | 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 |
| Dasatinib 70 mg BID | 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 | 6 participants |
| Dasatinib 70 mg BID | 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 | 1 participants |
| Dasatinib 70 mg BID | 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 | 8 participants |
| Dasatinib 70 mg BID | 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 | 19 participants |
Secondary
Number of Participants With Abnormalities (Grade 1 or 2) in Partial Thromboplastin Time (PTT)
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.
Population: All treated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib 100 mg BID | Number of Participants With Abnormalities (Grade 1 or 2) in Partial Thromboplastin Time (PTT) | 0 Participants |
| Dasatinib 70 mg BID | Number of Participants With Abnormalities (Grade 1 or 2) in Partial Thromboplastin Time (PTT) | 0 Participants |
Secondary
Number of Participants With Abnormalities (Grade 1 or 2) in Prothrombin Time (PT)
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.
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib 100 mg BID | Number of Participants With Abnormalities (Grade 1 or 2) in Prothrombin Time (PT) | Grade 1 | 3 participants |
| Dasatinib 100 mg BID | Number of Participants With Abnormalities (Grade 1 or 2) in Prothrombin Time (PT) | Grade 2 | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Abnormalities (Grade 1 or 2) in Prothrombin Time (PT) | Grade 1 | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Abnormalities (Grade 1 or 2) in Prothrombin Time (PT) | Grade 2 | 0 participants |
Secondary
Number of Participants With Abnormal Vital Signs Measurements
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)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib 100 mg BID | Number of Participants With Abnormal Vital Signs Measurements | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Abnormal Vital Signs Measurements | 0 participants |
Secondary
Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study
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.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib 100 mg BID | Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study | 3 Participants |
| Dasatinib 70 mg BID | Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study | 1 Participants |
Secondary
Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements
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.
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements | Granulocytes | 3 participants |
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements | Hemoglobin | 0 participants |
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements | Platelet Count | 0 participants |
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements | Leukocytes | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements | Leukocytes | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements | Granulocytes | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements | Platelet Count | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements | Hemoglobin | 0 participants |
Secondary
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase
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.
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib 100 mg BID | 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 |
| Dasatinib 100 mg BID | 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 |
| Dasatinib 100 mg BID | 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 |
| Dasatinib 70 mg BID | 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 |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase | Alanine aminotransferase | 3 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase | Aspartate aminotransferase | 3 participants |
Secondary
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium
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.
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | High calcium | 0 participants |
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | Low calcium | 0 participants |
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | High potassium | 0 participants |
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | Low potassium | 1 participants |
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | High magnesium | 0 participants |
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | Low magnesium | 0 participants |
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | High sodium | 0 participants |
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | Low sodium | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | Low sodium | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | High calcium | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | High magnesium | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | Low calcium | 1 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | High sodium | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | High potassium | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | Low magnesium | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium | Low potassium | 0 participants |
Secondary
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total).
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.
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total). | Creatinine | 0 participants |
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total). | Bicarbonate | 0 participants |
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total). | Inorganic Phosphorus | 1 participants |
| Dasatinib 100 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total). | Bilirubin, Total | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total). | Bilirubin, Total | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total). | Creatinine | 0 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total). | Inorganic Phosphorus | 2 participants |
| Dasatinib 70 mg BID | Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total). | Bicarbonate | 0 participants |
Secondary
Number of Participants With Identified Electrocardiogram (ECG) Abnormalities
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).
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib 100 mg BID | Number of Participants With Identified Electrocardiogram (ECG) Abnormalities | 4 participants |
| Dasatinib 70 mg BID | Number of Participants With Identified Electrocardiogram (ECG) Abnormalities | 3 participants |
Secondary
Percentage Change in Tumor Biomarkers
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
Population: 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.
Secondary
Percentage of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study
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
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib 100 mg BID | 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 |
| Dasatinib 70 mg BID | Percentage of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study | 5.0 percentage of participants |
Secondary
Profiling of Messenger-ribonucleic Acid (mRNA) Expression: mRNA Signal Intensity
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
Population: 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.
Secondary
Proportion of Participants With Progression-Free Survival (PFS) at 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.
Time frame: Weeks 9, 17, and 25
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Dasatinib 100 mg BID | Proportion of Participants With Progression-Free Survival (PFS) at Weeks 9, 17, and 25 | Week 9 | 0.40 Proportion of Participants | 0.13 |
| Dasatinib 100 mg BID | Proportion of Participants With Progression-Free Survival (PFS) at Weeks 9, 17, and 25 | Week 17 | 0.32 Proportion of Participants | 0.13 |
| Dasatinib 100 mg BID | Proportion of Participants With Progression-Free Survival (PFS) at Weeks 9, 17, and 25 | Week 25 | 0.21 Proportion of Participants | 0.12 |
| Dasatinib 70 mg BID | Proportion of Participants With Progression-Free Survival (PFS) at Weeks 9, 17, and 25 | Week 9 | 0.35 Proportion of Participants | 0.12 |
| Dasatinib 70 mg BID | Proportion of Participants With Progression-Free Survival (PFS) at Weeks 9, 17, and 25 | Week 17 | 0.14 Proportion of Participants | 0.09 |
| Dasatinib 70 mg BID | Proportion of Participants With Progression-Free Survival (PFS) at Weeks 9, 17, and 25 | Week 25 | 0.00 Proportion of Participants | 0 |