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This study will determine whether the investigational drug dasatinib is effective in treatment of women with progressive advanced triple-negative breast cancer.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental |
| |
| 2 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dasatinib | Drug | Tablets, Oral, 100 mg, twice daily as long as the patient benefits (avg <6 months) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline to end of study drug therapy (up to 65 weeks). |
| 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. | Baseline to end of study drug therapy (up to 65 weeks). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ucsf-Comprehensive Cancer Center | San Francisco | California | 94143 | United States | ||
| Mayo Clinic Jacksonville |
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)
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Number | participants | Baseline to end of study drug therapy (up to 65 weeks). |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Participants | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| MYOPERICARDITIS | Cardiac disorders | MedDRA 11.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| DRY EYE | Eye disorders | MedDRA 11.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| BMS Study Director | Bristol-Myers Squibb | Clinical.Trials@bms.com |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009362 | Neoplasm Metastasis |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D000069439 | Dasatinib |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
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| Dasatinib | Drug | Tablets, Oral, 70 mg, twice daily as long as the patient benefits (avg <6 months) |
|
| Baseline to 16 weeks. |
| 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. | Baseline to 16 weeks |
| 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. | Weeks 9, 17, and 25 |
| 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. | Baseline to end of study drug therapy (up to 53.86 weeks) |
| Mean Plasma Concentration at Week 3 | Mean plasma concentration was obtained directly from the concentration-time data. | At pre-dose and 1, 3, 6 and 12 hours after each dose administration |
| Mean Plasma Concentration at Week 7 | Mean plasma concentration was obtained directly from the concentration-time data. | At pre-dose and 1, 3, 6 and 12 hours after each dose administration |
| 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. | Baseline, Week 3 and Week 5 |
| 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. | Baseline, Week 3 and Week 5 |
| 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. | Baseline |
| 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. | Baseline |
| 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. | From start of study drug therapy up to 30 days after the last dose. |
| 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. | From start of study drug therapy up to 30 days after the last dose. |
| 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. | From start of study drug therapy up to 30 days after the last dose. |
| 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. | Throughout study, from start of study drug therapy up to 30 days after the last dose. |
| 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. | Throughout study, from start of study drug therapy up to 30 days after the last dose. |
| 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. | Throughout study, from start of study drug therapy up to 30 days after the last dose. |
| 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. | Throughout study, from start of study drug therapy up to 30 days after the last dose. |
| 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. | Throughout study, from start of study drug therapy up to 30 days after the last dose. |
| 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. | Throughout study, from start of study drug therapy up to 30 days after the last dose. |
| 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. | Baseline, Weeks 3, 9, 17 and 25, then every 8 weeks until the end of study treatment (up to 17 weeks). |
| 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. | At each study visit (Week 3, 5, 7, 9, 13, 17 and 25) and end of treatment (up to 17 weeks) |
| Jacksonville |
| Florida |
| 32224 |
| United States |
| Dana-Farber Cancer Inst | Boston | Massachusetts | 02115 | United States |
| Montefiore Medical Center | The Bronx | New York | 10461 | United States |
| University Of Texas Md Anderson Cancer Ctr | Houston | Texas | 77030 | United States |
| Local Institution | Paris | 75231 | France |
| Local Institution | Toulouse | 31052 | France |
| Local Institution | Modena | 41100 | Italy |
| Local Institution | Barcelona | 08035 | Spain |
| Local Institution | Lleida | 25198 | Spain |
| Subject request |
|
| Investigator Decision |
|
| Adverse event unrelated to study drug |
|
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| OG001 | 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. |
|
|
| 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. | 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. | Posted | Number | Participants | Baseline to 16 weeks. |
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline to 16 weeks |
|
|
|
| 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. | All treated participants | Posted | Number | Proportion of Participants | Weeks 9, 17, and 25 |
|
|
|
| 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. | Response-evaluable participants who achieved a complete response (CR) or partial response (PR) | Posted | Mean | Full Range | weeks | Baseline to end of study drug therapy (up to 53.86 weeks) |
|
|
|
| Secondary | Mean Plasma Concentration at Week 3 | Mean plasma concentration was obtained directly from the concentration-time data. | Participants who were evaluable for pharmacokinetic analysis. "n" signifies the number of participants evaluable at each time point. | Posted | Mean | Standard Deviation | nanograms (ng)/mL | At pre-dose and 1, 3, 6 and 12 hours after each dose administration |
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline to end of study drug therapy (up to 65 weeks). |
|
|
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| Secondary | Mean Plasma Concentration at Week 7 | Mean plasma concentration was obtained directly from the concentration-time data. | Participants who were evaluable for pharmacokinetic analysis. "n" signifies the number of participants evaluable at each time point. | Posted | Mean | Standard Deviation | nanograms (ng)/mL | At pre-dose and 1, 3, 6 and 12 hours after each dose administration |
|
|
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| 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. | Participants who were evaluable for pharmacodynamic analysis. | Posted | Geometric Mean | 90% Confidence Interval | percentage of baseline | Baseline, Week 3 and Week 5 |
|
|
|
| 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. | Participants who were evaluable for pharmacodynamic analysis. | Posted | Geometric Mean | 90% Confidence Interval | percentage of baseline | Baseline, Week 3 and Week 5 |
|
|
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| 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. | 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. | Posted | Median | Inter-Quartile Range | percentage | Baseline |
|
|
| 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. | 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. | Posted | Number | log2 scale (unitless) | Baseline |
|
|
| 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. | All treated participants. | Posted | Number | participants | From start of study drug therapy up to 30 days after the last dose. |
|
|
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| 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. | All treated participants | Posted | Number | participants | From start of study drug therapy up to 30 days after the last dose. |
|
|
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| 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. | All treated participants | Posted | Number | participants | From start of study drug therapy up to 30 days after the last dose. |
|
|
|
| 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. | All treated participants | Posted | Number | participants | Throughout study, from start of study drug therapy up to 30 days after the last dose. |
|
|
|
| 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. | All treated participants | Posted | Number | participants | Throughout study, from start of study drug therapy up to 30 days after the last dose. |
|
|
|
| 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. | All treated participants. | Posted | Number | Participants | Throughout study, from start of study drug therapy up to 30 days after the last dose. |
|
|
|
| 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. | All treated participants | Posted | Number | participants | Throughout study, from start of study drug therapy up to 30 days after the last dose. |
|
|
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| 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. | All treated participants | Posted | Number | participants | Throughout study, from start of study drug therapy up to 30 days after the last dose. |
|
|
|
| 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. | All treated participants | Posted | Number | participants | Throughout study, from start of study drug therapy up to 30 days after the last dose. |
|
|
|
| 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. | All treated participants | Posted | Number | participants | Baseline, Weeks 3, 9, 17 and 25, then every 8 weeks until the end of study treatment (up to 17 weeks). |
|
|
|
| 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. | All treated participants | Posted | Number | participants | At each study visit (Week 3, 5, 7, 9, 13, 17 and 25) and end of treatment (up to 17 weeks) |
|
|
|
| 14 |
| 44 |
| 44 |
| 44 |
| PERICARDIAL EFFUSION | Cardiac disorders | MedDRA 11.0 | Systematic Assessment |
|
| HYPOTENSION | Vascular disorders | MedDRA 11.0 | Systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| ASCITES | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| VOMITING | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| DYSPHAGIA | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| CONSTIPATION | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| INFECTION | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| PNEUMONIA | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| RENAL FAILURE ACUTE | Renal and urinary disorders | MedDRA 11.0 | Systematic Assessment |
|
| PERIORBITAL OEDEMA | Skin and subcutaneous tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| COSTOCHONDRITIS | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| MUSCULOSKELETAL CHEST PAIN | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| HAEMOPTYSIS | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| PNEUMONITIS | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| PLEURAL EFFUSION | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| RESPIRATORY FAILURE | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| PYREXIA | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| GENERALISED OEDEMA | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| GENERAL PHYSICAL HEALTH DETERIORATION | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| MALIGNANT NEOPLASM PROGRESSION | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.0 | Systematic Assessment |
|
| WEIGHT DECREASED | Investigations | MedDRA 11.0 | Systematic Assessment |
|
| ALANINE AMINOTRANSFERASE | Investigations | MedDRA 11.0 | Systematic Assessment |
|
| ASPARTATE AMINOTRANSFERASE | Investigations | MedDRA 11.0 | Systematic Assessment |
|
| ELECTROCARDIOGRAM QT PROLONGED | Investigations | MedDRA 11.0 | Systematic Assessment |
|
| FLUSHING | Vascular disorders | MedDRA 11.0 | Systematic Assessment |
|
| HOT FLUSH | Vascular disorders | MedDRA 11.0 | Systematic Assessment |
|
| ANXIETY | Psychiatric disorders | MedDRA 11.0 | Systematic Assessment |
|
| INSOMNIA | Psychiatric disorders | MedDRA 11.0 | Systematic Assessment |
|
| HEADACHE | Nervous system disorders | MedDRA 11.0 | Systematic Assessment |
|
| DIZZINESS | Nervous system disorders | MedDRA 11.0 | Systematic Assessment |
|
| PARAESTHESIA | Nervous system disorders | MedDRA 11.0 | Systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| VOMITING | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| DIARRHOEA | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| DYSPEPSIA | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| STOMATITIS | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| CONSTIPATION | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| ABDOMINAL DISTENSION | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| URINARY TRACT INFECTION | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| ANOREXIA | Metabolism and nutrition disorders | MedDRA 11.0 | Systematic Assessment |
|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA 11.0 | Systematic Assessment |
|
| NEUTROPENIA | Blood and lymphatic system disorders | MedDRA 11.0 | Systematic Assessment |
|
| RASH | Skin and subcutaneous tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| ERYTHEMA | Skin and subcutaneous tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| PRURITUS | Skin and subcutaneous tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| MUSCULOSKELETAL PAIN | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| MUSCULOSKELETAL CHEST PAIN | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| PLEURAL EFFUSION | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| PAIN | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| FATIGUE | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| PYREXIA | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| ASTHENIA | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| CHEST PAIN | General disorders | MedDRA 11.0 | Systematic Assessment |
|
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.
| D017437 |
| Skin and Connective Tissue Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020969 | Disease Attributes |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| Week 25 |
|
| 1 hour (n = 10, 10, 1) |
|
| 3 hour (n = 10, 10, 1) |
|
| 6 hour (n = 10, 10, 1) |
|
| 12 hour (n = 7, 6, 1) |
|
| 3 hour (n = 3, 6) |
|
| 6 hour (n = 2, 6) |
|
| 12 hour (n = 1, 5) |
|
| All adverse events (AEs) |
|
| Drug-related Grade 3 AEs |
|
| Drug-related AEs Leading to Discontinuation |
|
| Nausea |
|
| Dyspnea |
|
| Pleural Effusion |
|
| Rash |
|
| Headache |
|
| Anorexia |
|
| Vomiting |
|
| Cough |
|
| Abdominal pain |
|
| Platelet Count |
|
| Leukocytes |
|
| Aspartate aminotransferase |
|
| High potassium |
|
| Low potassium |
|
| High magnesium |
|
| Low magnesium |
|
| High sodium |
|
| Low sodium |
|
| Inorganic Phosphorus |
|
| Bilirubin, Total |
|