Safety and Efficacy of Exemestane Plus Dasatinib Versus Placebo for Advanced ER+ Breast Cancer
Study Details
Study Description
Brief Summary
The purpose of this study is to determine whether exemestane plus dasatinib will be well-tolerated and will increase progression-free survival (PFS) in the treatment of advanced estrogen-receptor positive (ER+) breast cancer after disease progression (PD) on a non-steroidal aromatase inhibitor (NSAI).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: A
|
Drug: Exemestane + Dasatinib
Tablets, Oral, Exemestane 25 mg + Dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity
Other Names:
|
| Placebo Comparator: B
|
Drug: Exemestane + Placebo
Tablets, Oral, Exemestane 25 mg + Placebo 100 mg, once daily, until disease progression or unacceptable toxicity
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) Distribution for Exemestane Plus Dasatinib vs Exemestane Plus Placebo [Prior to study therapy, at 8 week intervals until progression occurs (maximum participant PFS of 71 weeks)]
PFS= The time (weeks) from date of randomization to date of progressive disease(PD). PFS for each randomization arm was estimated using the Kaplan-Meier product-limit method. A point estimate and a 95% confidence interval (CI) for the median PFS was computed for each randomization arm using the Brookmeyer & Crowley method. PD=Increase (≥ 20%) in sum of longest diameters from smallest value during study (including baseline).
- Participants With Disease Progression or Death for Exemestane Plus Dasatinib vs Exemestane Plus Placebo [Prior to study therapy, at 8 week intervals until progression occurs. Maximum participant PFS of ____ months)]
PD is an increase (≥ 20%) in sum of longest diameters from smallest value during study (including baseline).
Secondary Outcome Measures
- Number of Participants With Best Overall Response [at 6 months]
Complete response (CR) = Disappearance of all measurable and non-measurable lesions, and no new lesions; Partial response (PR) = Decrease ≥30% from baseline in sum of longest diameters (LD) of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions. SD = Disease re-assessment not qualifying as CR, PR or PD(≥20% increase in sum of longest diameters from smallest value).
- Percentage of Participants With Clinical Benefit (CB) for Exemestane Plus Dasatinib Arm vs Exemestane Plus Placebo Arm at 6 Months [at 6 months]
CB = participants whose best response is CR, PR, or stable disease(SD). CR = Disappearance of all measurable and non-measurable lesions, and no new lesions; PR = Decrease ≥30% from baseline in sum of longest diameters of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions. SD = Disease re-assessment not qualifying as CR, PR or PD(≥20% increase in sum of longest diameters from smallest value). Confidence interval computed by Clopper-Pearson method.
- Percentage of Participants With Response in Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms [Prior to study therapy, at 8 week intervals until progression occurs (maximum participant response was 39 weeks)]
Response= Proportion of response-evaluable participants whose best response is CR or PR. Confidence intervals was computed using the Clopper-Pearson method. CR = Disappearance of all measurable and non-measurable lesions, and no new lesions; PR = Decrease ≥30% from baseline in sum of longest diameters of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions.
- Participants With Freedom-From-Progression (FFP) at 6 Months [at 6 months]
FFP at month 6 is defined for the randomized participants who had the probability of neither progressing nor dying before 6 months.
- Time to Response for Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms [Prior to study therapy, at 8 week intervals until CR or PR. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug, whichever is longer]
Time to response is defined as time from first dose of study therapy until measurement criteria are first met for PR or CR (whichever is recorded first). CR = Disappearance of all measurable and non-measurable lesions, and no new lesions; PR = Decrease ≥30% from baseline in sum of longest diameters of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions.
- Duration of Response for Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms [Prior to study therapy, at 8 week intervals. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug, whichever is longer.]
Duration of response is defined as the time from date that measurement criteria are first met for PR or CR until first date of documented PD or death. CR = Disappearance of all measurable and non-measurable lesions, and no new lesions; PR = Decrease ≥30% from baseline in sum of longest diameters of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions. PD=Increase (≥ 20%) in sum of longest diameters from smallest value during study (including baseline).
- Changes in Participant-reported Pain Intensity in Participants With Bone Metastasis [Start of study, at treatment start, after 2, 4, and 8 weeks of therapy and every 8 weeks thereafter, at end-of-treatment. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug.]
Pain intensity evaluated by administration of the Brief Pain Inventory - Short Form (BPI-sf). The BPI-sf is a psychometrically-validated instrument which measures both pain severity and functional interference caused by pain using an 11-point numerical rating scale. Severity of pain at its "worst", "least" and "on average" in the last 24 hours, and "right now" (ie, at the time the questionnaire is being filled out) is recorded using anchors of "no pain" = "0" and "pain as bad as you can imagine" = "10".
- Changes in Markers of Bone Lysis in Participants With Bone Metastasis [Screening, Day 1, after week 2, 4, and week 8 and subsequently every 8 weeks, at end-of-treatment. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug.]
Assay for urinary N-telopeptide was used to evaluate Osteolytic activity.
- Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AEs (as Per National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 3.0) [From start of study drug therapy up to 30 days after the last dose. Median duration of therapy (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.]
AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded. Grade (GR)1 = mild, GR 2 = moderate, GR 3=severe, GR 4=life threatening, GR 5=death.
- Number of Participants With Grade 1-4 Hematology Abnormalities (as Per the NCI CTCAE, Version 3.0) [Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.]
Abnormalities were graded per NCI-CTC, Version 3.0 criteria. Grade (GR)1 = mild, GR 2 = moderate, GR 3 = severe, GR 4 = life threatening. Normal ranges are provided by the Local Laboratory and may vary according to sex and age. Granulocytes, GR 1;<LLN-1.5x 10^9/L, GR 2:<1.5-1.0x10^9/L, GR 3: <1.0 - 0.5x10^9/L, GR, 4: <0.5x10^9 /L; Hemoglobin, GR 1: <LLN-10.0 g/dL, GR 2: <10.0-8.0 g/dL, GR 3: <8.0-6.5 g/dL, GR, 4: <6.5g/dL; Platelets, GR 1: <LLN-75.0x10^9/L, GR 2: <75.0-50.0x10^9/L, GR 3: <50.0-25.0x10^9/L; Leukocytes, GR 1: <LLN-3.0x10^9/L, GR 2: <3.0-2.0x10^9/L, GR 4: <1.0x10^9/L.
- Number of Participants With Grade 1-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Bilirubin, Calcium, Creatinine, and Albumin (as Per the NCI CTCAE, Version 3.0) [Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.]
Grade (GR) 1 = mild, GR 2 = moderate, GR 3 = severe, GR 4 = life threatening). Normal ranges are provided by the Local Laboratory and may vary according to sex and age. Alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, GR 1: >ULN-2.5 x ULN (upper limit of normal), GR 2: >2.5-5.0 x ULN, GR 3: 5.0-20.0 x ULN; Low calcium, GR 1: <LLN - 8.0 mg/dL, GR 2: <8.0-7.0 mg/dL, GR 4:<6.0 mg/dL; High calcium, GR 1:>ULN - 11.5 mg/dL; bilirubin, GR 1: >ULN-1.5 x ULN,GR 3: >3-10 x ULN; Creatinine, GR1:>ULN-1.5 x ULN, GR2: >1.5-3.0 x ULN; Albumin, GR1:<LLN-3 g/dL,GR2:<3-2 g/dL.
- Number of Participants With Grade 1-4 Serum Chemistry Abnormalities in Potassium, Magnesium, Sodium, Phosphorous, Uric Acid, and Bicarbonate (as Per the NCI CTCAE, Version 3.0) [Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively.]
Grade (GR)1= mild, GR2= moderate, GR3= severe, GR4= life threatening. Ranges are provided by the local laboratory and may vary according to sex and age. Phosphorous, GR1:<LLN 2.5 mg/dL, GR2:<2.5-2.0 mg/dL, GR3: 1.0-<2.0 mg/dL; Low sodium,GR1:<LLN 130mmol/L, GR3:120-<130 mmol/L; High Magnesium, GR1 >ULN 3.0 mg/dL,GR 3:<0.3 0.8mg/dL; Uric acid, GR1:>ULN 10 mg/dL, GR4:>10 mg/dL; Low potassium, GR1:<LLN 3.0mmol/L,GR3:<3.0 2.5mmol/L; High potassium, GR1:>ULN-5.5 mmol/L, GR2:>5.5-6.0 mmol/L; Bicarbonate, GR1:<LLN-16 mmol/L; GR2:<16 - 11 mmol/L; Hig sodium, GR1:>ULN-150 mmol/L,GR2:>150-155 mmol/L.
- Number of Participants With Abnormalities in Vital Signs [Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment.]
- Number of Participants With Abnormalities in Electrocardiograms [Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment.]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically-documented invasive estrogen receptor positive breast cancer , with tumor tissue from prior surgery available for analysis
-
Prior therapy with a non-steroidal aromatase inhibitor
-
Recurrent or progressive advanced breast cancer (locally-advanced or metastatic)
-
Documented breast cancer with tumor ≤ 28 days prior to study entry
-
Women who are NOT of childbearing potential
-
Must be able to take oral medication
-
Performance Status 0 or 1
Exclusion Criteria:
-
Pleural or pericardial effusion or ascites (of any etiology; Grade ≥ 1) within 6 months prior to study entry
-
Any chemotherapy, immunotherapy < 6 months before study entry. Any targeted therapy (eg. lapatinib) < 6 months before study entry, unless given in combination with an NSAI
-
Any antitumor therapy, including radiotherapy or hormonal therapy, within 15 days prior to study entry
-
Prior exposure to exemestane, any Src-family kinase inhibitor including dasatinib, to agents intended to control osteolytic disease other than bisphosphonates, or to any investigational agent for breast cancer
-
Concurrent or previous malignant disease requiring chemotherapy or radiation treatment within the prior 3 years
-
Significant bleeding disorder, or ongoing or recent clinically-significant gastrointestinal bleeding
-
Any serious cardiac condition, including congestive heart failure or myocardial infarction within 6 months, uncontrolled angina, or Class III or IV heart disease as defined by the New York Heart Association, baseline ejection fraction ≤ 40%, diagnosed congenital long QT syndrome, clinically-significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes), QTc interval > 450 msec at baseline (Fridericia correction)
-
Hematologic abnormality Grade ≥ 2
-
Hypocalcemia of Grade ≥ 1
-
Any Chemistry abnormality of Grade ≥ 2 [except Grade 2 indirect bilirubin permitted if diagnosed Gilbert's disease]
-
Pregnant Women and Women of Childbearing Potential (WOCBP)
-
Extremely lactose intolerant, in the judgment of treating physician (100 mg dasatinib contains 135 mg lactose, posing a problem only if intolerance is severe)
-
Receiving any of the following concomitant medications: Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Subjects must discontinue drug use at least 7 days prior to starting dasatinib)
-
Potent inhibitors of CYP3A4 isoenzyme
-
Prisoners or subjects who are involuntarily incarcerated; or subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Compassionate Cancer Care Medical Group, Inc | Fountain Valley | California | United States | 92708 |
| 2 | Compassionate Cancer Care Medical Group Inc | Riverside | California | United States | 92501 |
| 3 | Pennsylvania Oncology/Hematology Associates | Philadelphia | Pennsylvania | United States | 19106 |
| 4 | The West Clinic | Memphis | Tennessee | United States | 38120 |
| 5 | Local Institution | Hradec Kralove | Czech Republic | 500 05 | |
| 6 | Local Institution | Prague 5 | Czech Republic | 150 06 | |
| 7 | Local Institution | Lille | France | 59000 | |
| 8 | Local Institution | Paris Cedex 13 | France | 75651 | |
| 9 | Local Institution | Saint-Cloud Cedex | France | 92211 | |
| 10 | Local Institution | Dublin | Ireland | 24 | |
| 11 | Local Institution | Gdansk | Poland | 80-462 | |
| 12 | Local Institution | Gdansk | Poland | 80-952 | |
| 13 | Local Institution | Lodz | Poland | 93-509 | |
| 14 | Local Institution | Opole | Poland | 45-060 | |
| 15 | Local Institution | Madrid | Spain | 28033 | |
| 16 | Local Institution | Madrid | Spain | 28041 | |
| 17 | Local Institution | Torrevieja | Spain | 03186 | |
| 18 | Local Institution | Vasteras | Sweden | 72189 | |
| 19 | Local Institution | Chelmsford | Essex | United Kingdom | CM1 7ET |
| 20 | Local Institution | London | Greater London | United Kingdom | NW1 2BU |
| 21 | Local Institution | Coventry | Warwickshire | United Kingdom | CV22DX |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- CA180-261
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Exemestane + Dasatinib | Exemestane + Placebo |
|---|---|---|
| Arm/Group Description | Oral dose of exemestane 25 mg + dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity | Oral dose of exemestane 25 mg + placebo 100 mg, once daily, until disease progression or unacceptable toxicity |
| Period Title: Overall Study | ||
| STARTED | 79 | 78 |
| COMPLETED | 68 | 61 |
| NOT COMPLETED | 11 | 17 |
Baseline Characteristics
| Arm/Group Title | Exemestane + Dasatinib | Exemestane + Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Oral dose of exemestane 25 mg + dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity | Oral dose of exemestane 25 mg + placebo 100 mg, once daily, until disease progression or unacceptable toxicity | Total of all reporting groups |
| Overall Participants | 79 | 78 | 157 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
63.2
(12.19)
|
60.1
(10.43)
|
61.7
(11.41)
|
| Age, Customized (participants) [Number] | |||
| < 50 years |
9
11.4%
|
10
12.8%
|
19
12.1%
|
| >=50 years |
69
87.3%
|
68
87.2%
|
137
87.3%
|
| Not reported |
1
1.3%
|
0
0%
|
1
0.6%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
78
98.7%
|
78
100%
|
156
99.4%
|
| Male |
1
1.3%
|
0
0%
|
1
0.6%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| White |
68
86.1%
|
58
74.4%
|
126
80.3%
|
| Asian |
11
13.9%
|
19
24.4%
|
30
19.1%
|
| Other |
0
0%
|
1
1.3%
|
1
0.6%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| Hispanic / Latino |
1
1.3%
|
0
0%
|
1
0.6%
|
| Not Hispanic / Not Latino |
9
11.4%
|
8
10.3%
|
17
10.8%
|
| Not reported |
69
87.3%
|
70
89.7%
|
139
88.5%
|
| Time from Initial diagnosis to randomization (months) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [months] |
97.63
(74.866)
|
87.09
(64.743)
|
92.46
(70.058)
|
| Setting of Non-steroidal Aromatase Inhibitor (participants) [Number] | |||
| Adjuvant |
27
34.2%
|
27
34.6%
|
54
34.4%
|
| Advanced |
52
65.8%
|
51
65.4%
|
103
65.6%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (participants) [Number] | |||
| 0=normal activity |
46
58.2%
|
46
59%
|
92
58.6%
|
| 1=symptoms, but fully ambulatory |
32
40.5%
|
30
38.5%
|
62
39.5%
|
| Not reported |
1
1.3%
|
2
2.6%
|
3
1.9%
|
| Symptomatic Bone Disease (participants) [Number] | |||
| No |
48
60.8%
|
46
59%
|
94
59.9%
|
| Yes |
31
39.2%
|
32
41%
|
63
40.1%
|
Outcome Measures
| Title | Progression Free Survival (PFS) Distribution for Exemestane Plus Dasatinib vs Exemestane Plus Placebo |
|---|---|
| Description | PFS= The time (weeks) from date of randomization to date of progressive disease(PD). PFS for each randomization arm was estimated using the Kaplan-Meier product-limit method. A point estimate and a 95% confidence interval (CI) for the median PFS was computed for each randomization arm using the Brookmeyer & Crowley method. PD=Increase (≥ 20%) in sum of longest diameters from smallest value during study (including baseline). |
| Time Frame | Prior to study therapy, at 8 week intervals until progression occurs (maximum participant PFS of 71 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. Participants who died without reporting tumor progression were considered to have progressed on the death date. Participants who neither progressed nor died were censored on the day of their last on-study tumor assessment or the first date of subsequent therapy. |
| Arm/Group Title | Exemestane + Dasatinib | Exemestane + Placebo |
|---|---|---|
| Arm/Group Description | Oral dose of exemestane 25 mg + dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity | Oral dose of exemestane 25 mg + placebo 100 mg, once daily, until disease progression or unacceptable toxicity |
| Measure Participants | 79 | 78 |
| Median (95% Confidence Interval) [weeks] |
18.1
|
16.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Exemestane + Dasatinib, Exemestane + Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.148 |
| Comments | ||
| Method | Un-stratified log-rank test | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.82 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Best Overall Response |
|---|---|
| Description | Complete response (CR) = Disappearance of all measurable and non-measurable lesions, and no new lesions; Partial response (PR) = Decrease ≥30% from baseline in sum of longest diameters (LD) of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions. SD = Disease re-assessment not qualifying as CR, PR or PD(≥20% increase in sum of longest diameters from smallest value). |
| Time Frame | at 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response-evaluable participants: All treated participants who had measurable disease at baseline and at least one on-study tumor assessment. Treated participants without on-study tumor assessment due to rapid progression or study drug toxicity were included in the response-evaluable population as non-responders. |
| Arm/Group Title | Exemestane + Dasatinib | Exemestane + Placebo |
|---|---|---|
| Arm/Group Description | Oral dose of exemestane 25 mg + dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity | Oral dose of exemestane 25 mg + placebo 100 mg, once daily, until disease progression or unacceptable toxicity |
| Measure Participants | 49 | 49 |
| Complete response (CR) |
0
0%
|
0
0%
|
| Partial response (PR) |
3
3.8%
|
0
0%
|
| Stable Disease (SD) |
21
26.6%
|
14
17.9%
|
| Disease Progression |
15
19%
|
23
29.5%
|
| Unable to assess |
2
2.5%
|
1
1.3%
|
| Not reported |
8
10.1%
|
11
14.1%
|
| Title | Percentage of Participants With Clinical Benefit (CB) for Exemestane Plus Dasatinib Arm vs Exemestane Plus Placebo Arm at 6 Months |
|---|---|
| Description | CB = participants whose best response is CR, PR, or stable disease(SD). CR = Disappearance of all measurable and non-measurable lesions, and no new lesions; PR = Decrease ≥30% from baseline in sum of longest diameters of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions. SD = Disease re-assessment not qualifying as CR, PR or PD(≥20% increase in sum of longest diameters from smallest value). Confidence interval computed by Clopper-Pearson method. |
| Time Frame | at 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response-evaluable participants: All treated participants who had measurable disease at baseline and at least one on-study tumor assessment. Treated participants without on-study tumor assessment due to rapid progression or study drug toxicity were included in the response-evaluable population as non-responders. |
| Arm/Group Title | Exemestane + Dasatinib | Exemestane + Placebo |
|---|---|---|
| Arm/Group Description | Oral dose of exemestane 25 mg + dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity | Oral dose of exemestane 25 mg + placebo 100 mg, once daily, until disease progression or unacceptable toxicity |
| Measure Participants | 49 | 49 |
| Number (95% Confidence Interval) [percentage of participants] |
30.61
38.7%
|
12.24
15.7%
|
| Title | Percentage of Participants With Response in Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms |
|---|---|
| Description | Response= Proportion of response-evaluable participants whose best response is CR or PR. Confidence intervals was computed using the Clopper-Pearson method. CR = Disappearance of all measurable and non-measurable lesions, and no new lesions; PR = Decrease ≥30% from baseline in sum of longest diameters of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions. |
| Time Frame | Prior to study therapy, at 8 week intervals until progression occurs (maximum participant response was 39 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response-evaluable participants: All treated participants who had measurable disease at baseline and at least one on-study tumor assessment. Treated participants without on-study tumor assessment due to rapid progression or study drug toxicity were included in the response-evaluable population as non-responders. |
| Arm/Group Title | Exemestane + Dasatinib | Exemestane + Placebo |
|---|---|---|
| Arm/Group Description | Oral dose of exemestane 25 mg + dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity | Oral dose of exemestane 25 mg + placebo 100 mg, once daily, until disease progression or unacceptable toxicity |
| Measure Participants | 49 | 49 |
| Number (95% Confidence Interval) [percentage of participants] |
6.12
7.7%
|
0
0%
|
| Title | Participants With Freedom-From-Progression (FFP) at 6 Months |
|---|---|
| Description | FFP at month 6 is defined for the randomized participants who had the probability of neither progressing nor dying before 6 months. |
| Time Frame | at 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to Response for Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms |
|---|---|
| Description | Time to response is defined as time from first dose of study therapy until measurement criteria are first met for PR or CR (whichever is recorded first). CR = Disappearance of all measurable and non-measurable lesions, and no new lesions; PR = Decrease ≥30% from baseline in sum of longest diameters of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions. |
| Time Frame | Prior to study therapy, at 8 week intervals until CR or PR. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug, whichever is longer |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Duration of Response for Exemestane Plus Dasatinib Arm and Exemestane Plus Placebo Arms |
|---|---|
| Description | Duration of response is defined as the time from date that measurement criteria are first met for PR or CR until first date of documented PD or death. CR = Disappearance of all measurable and non-measurable lesions, and no new lesions; PR = Decrease ≥30% from baseline in sum of longest diameters of all measurable lesions, with neither appearance of new lesions nor unequivocal progression of non-measurable lesions. PD=Increase (≥ 20%) in sum of longest diameters from smallest value during study (including baseline). |
| Time Frame | Prior to study therapy, at 8 week intervals. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug, whichever is longer. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Changes in Participant-reported Pain Intensity in Participants With Bone Metastasis |
|---|---|
| Description | Pain intensity evaluated by administration of the Brief Pain Inventory - Short Form (BPI-sf). The BPI-sf is a psychometrically-validated instrument which measures both pain severity and functional interference caused by pain using an 11-point numerical rating scale. Severity of pain at its "worst", "least" and "on average" in the last 24 hours, and "right now" (ie, at the time the questionnaire is being filled out) is recorded using anchors of "no pain" = "0" and "pain as bad as you can imagine" = "10". |
| Time Frame | Start of study, at treatment start, after 2, 4, and 8 weeks of therapy and every 8 weeks thereafter, at end-of-treatment. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Changes in Markers of Bone Lysis in Participants With Bone Metastasis |
|---|---|
| Description | Assay for urinary N-telopeptide was used to evaluate Osteolytic activity. |
| Time Frame | Screening, Day 1, after week 2, 4, and week 8 and subsequently every 8 weeks, at end-of-treatment. Participants will remain on study (ie, last visit) until disease progression or 30 days after the last dose of study drug. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AEs (as Per National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 3.0) |
|---|---|
| Description | AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded. Grade (GR)1 = mild, GR 2 = moderate, GR 3=severe, GR 4=life threatening, GR 5=death. |
| Time Frame | From start of study drug therapy up to 30 days after the last dose. Median duration of therapy (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants. |
| Arm/Group Title | Exemestane + Dasatinib | Exemestane + Placebo |
|---|---|---|
| Arm/Group Description | Oral dose of exemestane 25 mg + dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity | Oral dose of exemestane 25 mg + placebo 100 mg, once daily, until disease progression or unacceptable toxicity |
| Measure Participants | 79 | 76 |
| All Deaths |
10
12.7%
|
2
2.6%
|
| All SAEs |
22
27.8%
|
13
16.7%
|
| Drug-related SAEs |
10
12.7%
|
4
5.1%
|
| AEs leading to discontinuation |
20
25.3%
|
6
7.7%
|
| All AEs |
77
97.5%
|
67
85.9%
|
| Drug-related AEs |
70
88.6%
|
48
61.5%
|
| Drug-related Grade 3/4 AEs |
26
32.9%
|
8
10.3%
|
| Drug-related Grade 5 AEs |
0
0%
|
1
1.3%
|
| Title | Number of Participants With Grade 1-4 Hematology Abnormalities (as Per the NCI CTCAE, Version 3.0) |
|---|---|
| Description | Abnormalities were graded per NCI-CTC, Version 3.0 criteria. Grade (GR)1 = mild, GR 2 = moderate, GR 3 = severe, GR 4 = life threatening. Normal ranges are provided by the Local Laboratory and may vary according to sex and age. Granulocytes, GR 1;<LLN-1.5x 10^9/L, GR 2:<1.5-1.0x10^9/L, GR 3: <1.0 - 0.5x10^9/L, GR, 4: <0.5x10^9 /L; Hemoglobin, GR 1: <LLN-10.0 g/dL, GR 2: <10.0-8.0 g/dL, GR 3: <8.0-6.5 g/dL, GR, 4: <6.5g/dL; Platelets, GR 1: <LLN-75.0x10^9/L, GR 2: <75.0-50.0x10^9/L, GR 3: <50.0-25.0x10^9/L; Leukocytes, GR 1: <LLN-3.0x10^9/L, GR 2: <3.0-2.0x10^9/L, GR 4: <1.0x10^9/L. |
| Time Frame | Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants. |
| Arm/Group Title | Exemestane + Dasatinib | Exemestane + Placebo |
|---|---|---|
| Arm/Group Description | Oral dose of exemestane 25 mg + dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity | Oral dose of exemestane 25 mg + placebo 100 mg, once daily, until disease progression or unacceptable toxicity |
| Measure Participants | 79 | 76 |
| Granulocytes; Grade 1 |
18
22.8%
|
9
11.5%
|
| Granulocytes; Grade 2 |
10
12.7%
|
1
1.3%
|
| Granulocytes; Grade 3 |
2
2.5%
|
0
0%
|
| Granulocytes; Grade 4 |
0
0%
|
2
2.6%
|
| Granulocytes; Grade Not reported |
2
2.5%
|
0
0%
|
| Hemoglobin; Grade 1 |
42
53.2%
|
21
26.9%
|
| Hemoglobin; Grade 2 |
11
13.9%
|
6
7.7%
|
| Hemoglobin; Grade 3 |
1
1.3%
|
2
2.6%
|
| Hemoglobin; Grade 4 |
1
1.3%
|
2
2.6%
|
| Hemoglobin; Grade Not reported |
2
2.5%
|
0
0%
|
| Platelet Count; Grade 1 |
10
12.7%
|
2
2.6%
|
| Platelet Count; Grade 2 |
2
2.5%
|
1
1.3%
|
| Platelet Count; Grade 3 |
0
0%
|
1
1.3%
|
| Platelet Count; Grade Not reported |
2
2.5%
|
0
0%
|
| Leukocytes; Grade 1 |
23
29.1%
|
12
15.4%
|
| Leukocytes; Grade 2 |
7
8.9%
|
2
2.6%
|
| Leukocytes; Grade 4 |
0
0%
|
1
1.3%
|
| Leukocytes; Grade Not reported |
2
2.5%
|
0
0%
|
| Title | Number of Participants With Grade 1-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Bilirubin, Calcium, Creatinine, and Albumin (as Per the NCI CTCAE, Version 3.0) |
|---|---|
| Description | Grade (GR) 1 = mild, GR 2 = moderate, GR 3 = severe, GR 4 = life threatening). Normal ranges are provided by the Local Laboratory and may vary according to sex and age. Alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, GR 1: >ULN-2.5 x ULN (upper limit of normal), GR 2: >2.5-5.0 x ULN, GR 3: 5.0-20.0 x ULN; Low calcium, GR 1: <LLN - 8.0 mg/dL, GR 2: <8.0-7.0 mg/dL, GR 4:<6.0 mg/dL; High calcium, GR 1:>ULN - 11.5 mg/dL; bilirubin, GR 1: >ULN-1.5 x ULN,GR 3: >3-10 x ULN; Creatinine, GR1:>ULN-1.5 x ULN, GR2: >1.5-3.0 x ULN; Albumin, GR1:<LLN-3 g/dL,GR2:<3-2 g/dL. |
| Time Frame | Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants. |
| Arm/Group Title | Exemestane + Dasatinib | Exemestane + Placebo |
|---|---|---|
| Arm/Group Description | Oral dose of exemestane 25 mg + dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity | Oral dose of exemestane 25 mg + placebo 100 mg, once daily, until disease progression or unacceptable toxicity |
| Measure Participants | 79 | 76 |
| Alkaline Phosphatase; Grade 1 |
20
25.3%
|
15
19.2%
|
| Alkaline Phosphatase; Grade 2 |
3
3.8%
|
10
12.8%
|
| Alkaline Phosphatase; Grade 3 |
2
2.5%
|
0
0%
|
| Alkaline Phosphatase; Grade Not reported |
2
2.5%
|
0
0%
|
| Alanine Aminotransferase; Grade 1 |
38
48.1%
|
16
20.5%
|
| Alanine Aminotransferase; Grade 2 |
4
5.1%
|
3
3.8%
|
| Alanine Aminotransferase; Grade 3 |
0
0%
|
3
3.8%
|
| Alanine Aminotransferase; Grade Not reported |
2
2.5%
|
0
0%
|
| Aspartate Aminotransferase; Grade 1 |
34
43%
|
18
23.1%
|
| Aspartate Aminotransferase; Grade 2 |
7
8.9%
|
7
9%
|
| Aspartate Aminotransferase; Grade 3 |
3
3.8%
|
1
1.3%
|
| Aspartate Aminotransferase; Grade Not reported |
2
2.5%
|
0
0%
|
| Low Calcium ; Grade 1 |
16
20.3%
|
6
7.7%
|
| Low Calcium ; Grade 2 |
2
2.5%
|
1
1.3%
|
| Low Calcium ; Grade 4 |
1
1.3%
|
2
2.6%
|
| Low Calcium ; Grade Not reported |
2
2.5%
|
0
0%
|
| High Calcium ; Grade 1 |
8
10.1%
|
12
15.4%
|
| High Calcium ; Grade Not reported |
2
2.5%
|
0
0%
|
| Creatinine; Grade 1 |
13
16.5%
|
13
16.7%
|
| Creatinine; Grade 2 |
3
3.8%
|
1
1.3%
|
| Creatinine; Grade Not reported |
2
2.5%
|
0
0%
|
| Bilirubin; Grade 1 |
2
2.5%
|
6
7.7%
|
| Bilirubin; Grade 3 |
0
0%
|
1
1.3%
|
| Bilirubin; Grade Not reported |
3
3.8%
|
0
0%
|
| Albumin; Grade 1 |
9
11.4%
|
6
7.7%
|
| Albumin; Grade 2 |
6
7.6%
|
3
3.8%
|
| Albumin; Grade Not reported |
2
2.5%
|
0
0%
|
| Title | Participants With Disease Progression or Death for Exemestane Plus Dasatinib vs Exemestane Plus Placebo |
|---|---|
| Description | PD is an increase (≥ 20%) in sum of longest diameters from smallest value during study (including baseline). |
| Time Frame | Prior to study therapy, at 8 week intervals until progression occurs. Maximum participant PFS of ____ months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. Participants who died without reporting tumor progression were considered to have progressed on the death date. Participants who neither progressed nor died were censored on the day of their last on-study tumor assessment or the first date of subsequent therapy. |
| Arm/Group Title | Exemestane + Dasatinib | Exemestane + Placebo |
|---|---|---|
| Arm/Group Description | Oral dose of exemestane 25 mg + dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity | Oral dose of exemestane 25 mg + placebo 100 mg, once daily, until disease progression or unacceptable toxicity |
| Measure Participants | 79 | 78 |
| Disease Progression |
56
70.9%
|
59
75.6%
|
| Death |
4
5.1%
|
0
0%
|
| Censored |
19
24.1%
|
19
24.4%
|
| Title | Number of Participants With Grade 1-4 Serum Chemistry Abnormalities in Potassium, Magnesium, Sodium, Phosphorous, Uric Acid, and Bicarbonate (as Per the NCI CTCAE, Version 3.0) |
|---|---|
| Description | Grade (GR)1= mild, GR2= moderate, GR3= severe, GR4= life threatening. Ranges are provided by the local laboratory and may vary according to sex and age. Phosphorous, GR1:<LLN 2.5 mg/dL, GR2:<2.5-2.0 mg/dL, GR3: 1.0-<2.0 mg/dL; Low sodium,GR1:<LLN 130mmol/L, GR3:120-<130 mmol/L; High Magnesium, GR1 >ULN 3.0 mg/dL,GR 3:<0.3 0.8mg/dL; Uric acid, GR1:>ULN 10 mg/dL, GR4:>10 mg/dL; Low potassium, GR1:<LLN 3.0mmol/L,GR3:<3.0 2.5mmol/L; High potassium, GR1:>ULN-5.5 mmol/L, GR2:>5.5-6.0 mmol/L; Bicarbonate, GR1:<LLN-16 mmol/L; GR2:<16 - 11 mmol/L; Hig sodium, GR1:>ULN-150 mmol/L,GR2:>150-155 mmol/L. |
| Time Frame | Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. Median duration (on-study time) was 14.29 and 15.29 weeks for dasatinib and placebo groups, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants. |
| Arm/Group Title | Exemestane + Dasatinib | Exemestane + Placebo |
|---|---|---|
| Arm/Group Description | Oral dose of exemestane 25 mg + dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity | Oral dose of exemestane 25 mg + placebo 100 mg, once daily, until disease progression or unacceptable toxicity |
| Measure Participants | 79 | 76 |
| Low Sodium; Grade 1 |
16
20.3%
|
10
12.8%
|
| Low Sodium; Grade 3 |
1
1.3%
|
0
0%
|
| Low Sodium; Grade Not reported |
3
3.8%
|
0
0%
|
| Inorganic Phosphorus; Grade 1 |
2
2.5%
|
1
1.3%
|
| Inorganic Phosphorus; Grade 2 |
7
8.9%
|
8
10.3%
|
| Inorganic Phosphorus; Grade 3 |
5
6.3%
|
1
1.3%
|
| Inorganic Phosphorus; Grade Not reported |
3
3.8%
|
4
5.1%
|
| Low Magnesium; Grade 1 |
4
5.1%
|
6
7.7%
|
| Low Magnesium; Grade 3 |
1
1.3%
|
1
1.3%
|
| Low Magnesium; Grade 4 |
0
0%
|
1
1.3%
|
| Low Magnesium; Grade Not reported |
7
8.9%
|
2
2.6%
|
| Uric acid; Grade 1 |
16
20.3%
|
18
23.1%
|
| Uric acid; Grade 4 |
2
2.5%
|
0
0%
|
| Uric acid; Grade Not reported |
2
2.5%
|
0
0%
|
| Low Potassium; Grade 1 |
11
13.9%
|
4
5.1%
|
| Low Potassium; Grade 3 |
1
1.3%
|
0
0%
|
| Low Potassium; Grade Not reported |
3
3.8%
|
0
0%
|
| High Potassium; Grade 1 |
5
6.3%
|
6
7.7%
|
| High Potassium; Grade 2 |
2
2.5%
|
0
0%
|
| High Potassium; Grade Not reported |
3
3.8%
|
0
0%
|
| Bicarbonate; Grade 1 |
11
13.9%
|
8
10.3%
|
| Bicarbonate; Grade 2 |
0
0%
|
1
1.3%
|
| Bicarbonate; Grade Not reported |
19
24.1%
|
14
17.9%
|
| High Magnesium; Grade 1 |
10
12.7%
|
5
6.4%
|
| High Magnesium; Grade 2 |
2
2.5%
|
2
2.6%
|
| High Magnesium; Grade 3 |
2
2.5%
|
1
1.3%
|
| High Magnesium; Grade Not reported |
7
8.9%
|
2
2.6%
|
| High Sodium; Grade 1 |
2
2.5%
|
1
1.3%
|
| High Sodium; Grade 2 |
1
1.3%
|
0
0%
|
| High Sodium; Grade Not reported |
3
3.8%
|
0
0%
|
| Title | Number of Participants With Abnormalities in Vital Signs |
|---|---|
| Description | |
| Time Frame | Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Number of Participants With Abnormalities in Electrocardiograms |
|---|---|
| Description | |
| Time Frame | Data was collected prior treatment with the study drug, after week 2, 4, and week 8, every 8 weeks thereafter and at the end of the treatment. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Exemestane + Dasatinib | Exemestane + Placebo | ||
| Arm/Group Description | Oral dose of exemestane 25 mg + dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity | Oral dose of exemestane 25 mg + placebo 100 mg, once daily, until disease progression or unacceptable toxicity | ||
All Cause Mortality |
||||
| Exemestane + Dasatinib | Exemestane + Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Exemestane + Dasatinib | Exemestane + Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 22/79 (27.8%) | 13/76 (17.1%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/79 (0%) | 1/76 (1.3%) | ||
| Cardiac disorders | ||||
| Right ventricular dysfunction | 1/79 (1.3%) | 0/76 (0%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 1/79 (1.3%) | 0/76 (0%) | ||
| Vomiting | 2/79 (2.5%) | 2/76 (2.6%) | ||
| Abdominal pain | 0/79 (0%) | 1/76 (1.3%) | ||
| Colonic obstruction | 0/79 (0%) | 1/76 (1.3%) | ||
| Dysphagia | 1/79 (1.3%) | 0/76 (0%) | ||
| Nausea | 1/79 (1.3%) | 1/76 (1.3%) | ||
| General disorders | ||||
| Mucosal inflammation | 1/79 (1.3%) | 0/76 (0%) | ||
| Performance status decreased | 1/79 (1.3%) | 0/76 (0%) | ||
| Sudden death | 1/79 (1.3%) | 0/76 (0%) | ||
| Disease progression | 1/79 (1.3%) | 0/76 (0%) | ||
| Hepatobiliary disorders | ||||
| Hepatic function abnormal | 0/79 (0%) | 1/76 (1.3%) | ||
| Infections and infestations | ||||
| Lymphangitis | 1/79 (1.3%) | 0/76 (0%) | ||
| Pneumonia | 2/79 (2.5%) | 0/76 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Lower limb fracture | 1/79 (1.3%) | 0/76 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 1/79 (1.3%) | 0/76 (0%) | ||
| Dehydration | 0/79 (0%) | 1/76 (1.3%) | ||
| Hypercalcaemia | 0/79 (0%) | 1/76 (1.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 0/79 (0%) | 1/76 (1.3%) | ||
| Back pain | 0/79 (0%) | 1/76 (1.3%) | ||
| Bone pain | 1/79 (1.3%) | 1/76 (1.3%) | ||
| Pathological fracture | 1/79 (1.3%) | 0/76 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Renal cell carcinoma | 1/79 (1.3%) | 0/76 (0%) | ||
| Gastrointestinal carcinoma | 0/79 (0%) | 1/76 (1.3%) | ||
| Malignant neoplasm progression | 1/79 (1.3%) | 2/76 (2.6%) | ||
| Nervous system disorders | ||||
| Ischaemic stroke | 0/79 (0%) | 1/76 (1.3%) | ||
| Paraesthesia | 1/79 (1.3%) | 0/76 (0%) | ||
| Amnesia | 1/79 (1.3%) | 0/76 (0%) | ||
| Cerebral ischaemia | 0/79 (0%) | 1/76 (1.3%) | ||
| Cerebrovascular accident | 1/79 (1.3%) | 0/76 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pulmonary embolism | 2/79 (2.5%) | 0/76 (0%) | ||
| Pleural effusion | 7/79 (8.9%) | 1/76 (1.3%) | ||
| Pulmonary oedema | 1/79 (1.3%) | 0/76 (0%) | ||
| Dyspnoea | 6/79 (7.6%) | 3/76 (3.9%) | ||
| Vascular disorders | ||||
| Phlebitis | 1/79 (1.3%) | 0/76 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Exemestane + Dasatinib | Exemestane + Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 74/79 (93.7%) | 61/76 (80.3%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 7/79 (8.9%) | 6/76 (7.9%) | ||
| Cardiac disorders | ||||
| Palpitations | 6/79 (7.6%) | 2/76 (2.6%) | ||
| Eye disorders | ||||
| Vision blurred | 4/79 (5.1%) | 0/76 (0%) | ||
| Gastrointestinal disorders | ||||
| Constipation | 15/79 (19%) | 11/76 (14.5%) | ||
| Diarrhoea | 25/79 (31.6%) | 7/76 (9.2%) | ||
| Stomatitis | 1/79 (1.3%) | 4/76 (5.3%) | ||
| Vomiting | 20/79 (25.3%) | 14/76 (18.4%) | ||
| Abdominal pain | 6/79 (7.6%) | 3/76 (3.9%) | ||
| Abdominal pain upper | 3/79 (3.8%) | 4/76 (5.3%) | ||
| Dyspepsia | 5/79 (6.3%) | 5/76 (6.6%) | ||
| Nausea | 29/79 (36.7%) | 23/76 (30.3%) | ||
| General disorders | ||||
| Oedema peripheral | 7/79 (8.9%) | 2/76 (2.6%) | ||
| Pyrexia | 10/79 (12.7%) | 3/76 (3.9%) | ||
| Face oedema | 4/79 (5.1%) | 0/76 (0%) | ||
| Fatigue | 18/79 (22.8%) | 12/76 (15.8%) | ||
| Oedema | 5/79 (6.3%) | 0/76 (0%) | ||
| Asthenia | 21/79 (26.6%) | 8/76 (10.5%) | ||
| Influenza like illness | 4/79 (5.1%) | 0/76 (0%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 4/79 (5.1%) | 3/76 (3.9%) | ||
| Bronchitis | 4/79 (5.1%) | 0/76 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 6/79 (7.6%) | 2/76 (2.6%) | ||
| Aspartate aminotransferase increased | 6/79 (7.6%) | 2/76 (2.6%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 16/79 (20.3%) | 8/76 (10.5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 8/79 (10.1%) | 10/76 (13.2%) | ||
| Musculoskeletal chest pain | 4/79 (5.1%) | 4/76 (5.3%) | ||
| Back pain | 4/79 (5.1%) | 7/76 (9.2%) | ||
| Bone pain | 5/79 (6.3%) | 6/76 (7.9%) | ||
| Pain in extremity | 4/79 (5.1%) | 8/76 (10.5%) | ||
| Myalgia | 4/79 (5.1%) | 4/76 (5.3%) | ||
| Musculoskeletal pain | 4/79 (5.1%) | 6/76 (7.9%) | ||
| Nervous system disorders | ||||
| Dizziness | 6/79 (7.6%) | 2/76 (2.6%) | ||
| Headache | 21/79 (26.6%) | 14/76 (18.4%) | ||
| Psychiatric disorders | ||||
| Insomnia | 8/79 (10.1%) | 4/76 (5.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pleural effusion | 15/79 (19%) | 1/76 (1.3%) | ||
| Dyspnoea | 20/79 (25.3%) | 4/76 (5.3%) | ||
| Cough | 13/79 (16.5%) | 5/76 (6.6%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 5/79 (6.3%) | 1/76 (1.3%) | ||
| Rash | 12/79 (15.2%) | 5/76 (6.6%) | ||
| Dry skin | 4/79 (5.1%) | 0/76 (0%) | ||
| Pruritus | 4/79 (5.1%) | 4/76 (5.3%) | ||
| Vascular disorders | ||||
| Hot flush | 4/79 (5.1%) | 6/76 (7.9%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
| Name/Title | BMS Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| Clinical.Trials@bms.com |
- CA180-261