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Study of Dasatinib (BMS-354825) in Patients With Advanced Estrogen/Progesterone Receptor-positive (ER+/PR+) or Her2/Neu-positive (Her2/Neu+)Breast Cancer

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ClinicalTrials.gov Identifier: NCT00371345
Recruitment Status : Completed
First Posted : September 4, 2006
Results First Posted : November 5, 2010
Last Update Posted : April 26, 2011
Sponsor:
Information provided by:
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Breast Cancer
Metastasis
Interventions Drug: Dasatinib
Drug: Dasatinib 100 mg
Enrollment 92
Recruitment Details  
Pre-assignment Details A total of 92 participants were enrolled in the study. Twenty-two participants did not enter the treatment phase, 13 because they did not meet entry criteria and 9 for other reasons. The 70 participants treated in the single-arm were stratified by tumor type into Her2-amplified and ER/PgR positive tumors.
Arm/Group Title Her2/Neu-amplified Tumor Type ER and/or PgR Positive Tumor Type
Hide Arm/Group Description Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg. Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg.
Period Title: Overall Study
Started 24 46
Completed 0 0
Not Completed 24 46
Reason Not Completed
Disease Progression             21             35
Study Drug Toxicity             1             7
Adverse event(AE Unrelated to Study Drug             1             2
Participant Request             1             1
Participant Withdrew Consent             0             1
Arm/Group Title Her2/Neu-amplified Tumor Type ER and/or PgR Positive Tumor Type Total
Hide Arm/Group Description Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg. Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg. Total of all reporting groups
Overall Number of Baseline Participants 24 46 70
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 24 participants 46 participants 70 participants
52.2
(32 to 68)
54.3
(33 to 70)
53.6
(32 to 70)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 24 participants 46 participants 70 participants
<=50 years 8 16 24
>=50 years 16 30 46
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 46 participants 70 participants
Female
24
 100.0%
46
 100.0%
70
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 24 participants 46 participants 70 participants
France 9 2 11
United States 10 17 27
Argentina 0 6 6
Spain 4 8 12
Belgium 1 10 11
Peru 0 1 1
Italy 0 2 2
1.Primary Outcome
Title Number of Participants With Objective Response
Hide Description Tumor response was assessed according RECIST criteria: PR=at least 30% reduction in the sum of the LD of all target lesions in reference to the baseline sum LD, CR=Disappearance of all non-target lesions. Objective tumor response was defined as a PR or CR.
Time Frame From day of first treatment through Week 25 or at time of discontinuation from study treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable population (n=69): Response Evaluable=treated participants with ≥1 measurable lesion at baseline and ≥1 on-study tumor assessment. One participant was not evaluable (no on-study tumor assessment for other reason).
Arm/Group Title Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib Her2/Neu-amplified Tumor, 100 mg BID ER and/or PgR Positive Tumor, 70 mg BID Dasatinib ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
Hide Arm/Group Description:
Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg.
Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg.
Overall Number of Participants Analyzed 15 9 31 14
Measure Type: Number
Unit of Measure: participants
0 1 1 1
2.Primary Outcome
Title Percentage of Participants With Objective Response
Hide Description Tumor response was assessed according RECIST criteria: PR=at least 30% reduction in the sum of the LD of all target lesions in reference to the baseline sum LD, CR=Disappearance of all non-target lesions. Percentage of participants with objective tumor response was determined by the number of participants with PR or CR divided by the total number of response-evaluable participants.
Time Frame From day of first treatment through Week 25 or at time of discontinuation from study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable population (n=69): Response Evaluable=treated participants with ≥1 measurable lesion at baseline and ≥1 on-study tumor assessment; Non-responders=treated participants with no on-study tumor response assessment due to rapid disease progression/dasatinib toxicity. One participant was not evaluable (no on-study tumor assessment).
Arm/Group Title Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib Her2/Neu-amplified Tumor, 100 mg BID Dasatinib ER and/or PgR Positive Tumor, 70 mg BID Dasatinib ER and/or PgR Positive Tumor, 100 mg BID Dasatinib All Response-evaluable Participants
Hide Arm/Group Description:
Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg.
Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg.
Evaluable population (n=69): Response Evaluable=treated participants with ≥1 measurable lesion at baseline and ≥1 on-study tumor assessment; Non-responders=treated participants with no on-study tumor response assessment due to rapid disease progression/dasatinib toxicity. One participant was not evaluable (no on-study tumor assessment).
Overall Number of Participants Analyzed 15 9 31 14 69
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0
(0 to 0)
11.11
(0.28 to 48.25)
3.23
(0.08 to 16.70)
7.14
(0.18 to 33.87)
4.35
(0.91 to 12.18)
3.Primary Outcome
Title Best Overall Response
Hide Description Response assessed using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR)=disappearance of all target and non-target lesions; Partial Response (PR)=≥30% decrease in sum of longest diameter (LD) of target lesions; SD=small changes not meeting above criteria; Progressive Disease (PD)=appearance of new lesion(s), ≥ 20% increase in the sum of the LD of target lesions, or progression of existing non-target lesions; Clinical Progression (cPD)=deterioration related to disease requiring treatment without radiographic PD.
Time Frame From day of first treatment through Week 25 or at time of discontinuation from study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable population (n=69): Response Evaluable=treated participants with ≥1 measurable lesion at baseline and ≥1 on-study tumor assessment; Non-responders=treated participants with no on-study tumor response assessment due to rapid disease progression/dasatinib toxicity. One participant was not evaluable (no on-study tumor assessment).
Arm/Group Title Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib Her2/Neu-amplified Tumor, 100 mg BID ER and/or PgR Positive Tumor, 70 mg BID Dasatinib ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
Hide Arm/Group Description:
Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg.
Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg.
Overall Number of Participants Analyzed 15 9 31 14
Measure Type: Number
Unit of Measure: participants
Complete Response (CR) 0 0 0 0
Unconfirmed partial response 0 0 1 0
Partial Response (PR) 0 1 1 1
Stable Disease (SD) 2 2 5 3
Progressive Disease (PD) 12 4 15 7
Clinical Progression (cPD) 0 1 3 1
Discontinuation Due To Drug Toxicity (Tox) 1 1 5 2
No Reassessment -Reasons Other Than Tox/PD 0 0 1 0
4.Secondary Outcome
Title Number of Response-evaluable Participants With Disease Control (DCR)
Hide Description Disease control was defined in response-evaluable participants as having a best response of CR or PR (or uPR), or SD at/after 16 Weeks.
Time Frame From day of first treatment through Week 25 or at time of discontinuation from study treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable population (n=69): Response Evaluable=treated participants with ≥1 measurable lesion at baseline and ≥1 on-study tumor assessment; Non-responders=treated participants with no on-study tumor response assessment due to rapid disease progression/dasatinib toxicity. One participant was not evaluable (no on-study tumor assessment).
Arm/Group Title Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib Her2/Neu-amplified Tumor, 100 mg BID Dasatinib ER and/or PgR Positive Tumor, 70 mg BID Dasatinib ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
Hide Arm/Group Description:
Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg.
Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg.
Overall Number of Participants Analyzed 1 1 5 2
Measure Type: Number
Unit of Measure: participants
Participants with CR 0 0 0 0
Participants with unconfirmed PR (uCR) 0 0 1 0
Participants with PR 0 1 1 1
Participants with SD ≥16 weeks 1 0 3 1
Total Participants with DCR 1 1 5 2
5.Secondary Outcome
Title Percentage of Response-evaluable Participants With Disease Control (DCR)
Hide Description Disease control was defined in response-evaluable participants as having a best response of objective response (CR or PR) or SD at/after 16 Weeks.
Time Frame From day of first treatment through Week 25 or at time of discontinuation from study treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable population (n=69): Response Evaluable=treated participants with ≥1 measurable lesion at baseline and ≥1 on-study tumor assessment; Non-responders=treated participants with no on-study tumor response assessment due to rapid disease progression/dasatinib toxicity. One participant was not evaluable (no on-study tumor assessment).
Arm/Group Title Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib Her2/Neu-amplified Tumor, 100 mg BID Dasatinib ER and/or PgR Positive Tumor, 70 mg BID Dasatinib ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
Hide Arm/Group Description:
Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg.
Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg.
Overall Number of Participants Analyzed 15 9 31 14
Mean (95% Confidence Interval)
Unit of Measure: percentage of participants
6.67
(0.17 to 31.95)
11.11
(0.28 to 48.25)
16.13
(5.54 to 33.73)
14.29
(1.78 to 42.81)
6.Secondary Outcome
Title Number of Participants Who Progressed
Hide Description PFS was defined as time from first dosing date until the first date that Progressive Disease (PD) was observed.
Time Frame From Baseline (Week 0) to time of PD or discontinuation of last participant from study treatment (Week 45)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Treated subjects: All subjects who received at least one dose of dasatinib. The longest on-study observation for a participant was 45 weeks.
Arm/Group Title Her2/Neu-amplified Tumor ER and/or PgR Positive Tumor All Participants
Hide Arm/Group Description:
Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally dasatinib twice daily (BID).
Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally dasatinib twice daily (BID).
Dasatinib was administered orally at 70 mg BID (TDD=140 mg) or 100 mg BID (TDD=200 mg).
Overall Number of Participants Analyzed 24 46 70
Measure Type: Number
Unit of Measure: participants
22 39 61
7.Secondary Outcome
Title Median Progression Free Survival (PFS)
Hide Description PFS was defined as time from first dosing date until the first date that PD was observed. The distribution of PFS was estimated using the Kaplan-Meier product limit method. A two-sided 95% confidence interval (Brookmeyer and Crowley method) for the median PFS was computed.
Time Frame From Baseline (Week 0) to time of PD or discontinuation of last participant from study treatment (Week 45)
Hide Outcome Measure Data
Hide Analysis Population Description
All-Treated subjects: All subjects who received at least one dose of dasatinib. The longest on-study observation for a participant was 45 weeks.
Arm/Group Title Her2/Neu-amplified Tumor ER and/or PgR Positive Tumor
Hide Arm/Group Description:
Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally dasatinib twice daily (BID).
Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally dasatinib twice daily (BID).
Overall Number of Participants Analyzed 24 46
Median (95% Confidence Interval)
Unit of Measure: weeks
8.1
(7.1 to 9.3)
8.1
(7.7 to 8.7)
8.Secondary Outcome
Title Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25
Hide Description PFS was defined as time from first dosing date until the first date that progressive disease (PD) was observed.
Time Frame At Weeks 9, 17, and 25
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable population (n=69): Response Evaluable=treated participants with ≥1 measurable lesion at baseline and ≥1 on-study tumor assessment; Non-responders=treated participants with no on-study tumor response assessment due to rapid disease progression/dasatinib toxicity. One participant was not evaluable (no on-study tumor assessment).
Arm/Group Title Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib Her2/Neu-amplified Tumor, 100 mg BID Dasatinib ER and/or PgR Positive Tumor, 70 mg BID Dasatinib ER and/or PgR Positive Tumor, 100 mg BID Dasatinib
Hide Arm/Group Description:
Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
Participants with a Human epidermal growth factor (Her2/neu)–amplified tumor type (defined as 3+ by immunohistochemistry [IHC] or positive by fluorescent or chromogenic in situ hybridization [FISH or CISH] regardless of estrogen receptor [ER]/progesterone receptor [PgR] status) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg.
Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally 70 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 140 mg.
Participants with ER and/or PgR positive tumor types (defined as >10% of cells positive by IHC [unless Her2/neu–amplified]) received orally 100 mg of dasatinib twice daily (BID) for a total daily dose (TDD) of 200 mg.
Overall Number of Participants Analyzed 15 9 32 14
Measure Type: Number
Unit of Measure: percentage of participants
Week 9 21 50 32 33
Week 17 7 25 18 25
Week 25 0 13 7 17
9.Secondary Outcome
Title Duration Of Objective Response
Hide Description Duration of objective response was defined as the time (in weeks) between the first date that criteria for CR or PR were met and the first date that progressive disease (PD) or clinical progressive disease (cPD) was observed. Date of death was used as PD date for participants who died before reporting PD. Participants who neither progressed nor died were censored at the date of their last tumor assessment.
Time Frame the time (in weeks) between the first date that criteria for PR were met and the first date that PD or cPD was observed
Hide Outcome Measure Data
Hide Analysis Population Description
Of 69 response-evaluable participants, three had an objective response of PR.
Arm/Group Title Participant CA180088-18-88009, HER-2 Group Participant CA180088-16-88002, ER and/or PgR Group Participant CA180088-29-88085, ER and/or PgR Group
Hide Arm/Group Description:
Participant with Human epidermal growth factor (Her2/neu)–amplified tumor type (also positive for ER and PgR) who received 100 mg dasatinib BID.
Participant with ER and PgR–amplified tumor type who received 100 mg dasatinib BID
Participant with ER and PgR–amplified tumor type who received 70 mg dasatinib BID
Overall Number of Participants Analyzed 1 1 1
Measure Type: Number
Unit of Measure: weeks
31.14 18.14 8.29
10.Secondary Outcome
Title Number of Participants With Death, Adverse Events (AEs), and AEs Leading to Discontinuation
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.
Time Frame Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All-Treated participants: All participants who received at least one dose of dasatinib.
Arm/Group Title Dasatinib 70 mg Dasatinib 100 mg
Hide Arm/Group Description:
Dasatinib was administered orally at 70 mg BID, for a TDD of 140 mg.
Dasatinib was administered orally at 100 mg BID, for a total daily dose (TDD) of 200 mg.
Overall Number of Participants Analyzed 23 47
Measure Type: Number
Unit of Measure: participants
All Deaths 6 6
All AEs 23 47
AEs Leading to Discontinuation 5 11
11.Secondary Outcome
Title Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities
Hide Description Normal ranges for laboratory abnormalities: granulocytes=1.5x10^3-8x10^3 mm^3 (range may have varied by institution); hemoglobin=12-16 g/dL; platelets=150-440x10^9c/L; partial thromboplastin time=27-37.1 seconds; alkaline phosphatase=38-126 U/L; alanine aminotransferase=15-48 U/L; aspartate aminotransferase=14-38 U/L; creatine=0.7-1.1 mg/dL; hypokalemia (potassium [K])=3.5-5mEq/L; hyponatremia (sodium [Na])=135-145 mEq/L; phosphorous=2.4-4.5 mg/dL; bilirubin=0-1.2. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening/disabling, Gr 5=Death.
Time Frame Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All-Treated participants: All participants who received at least one dose of dasatinib.
Arm/Group Title Dasatinib 70 mg Dasatinib 100 mg
Hide Arm/Group Description:
Dasatinib was administered orally at 70 mg BID, for a TDD of 140 mg.
Dasatinib was administered orally at 100 mg BID, for a total daily dose (TDD) of 200 mg.
Overall Number of Participants Analyzed 23 47
Measure Type: Number
Unit of Measure: participants
Granulocytes 1 1
Hemoglobin 0 1
Platelet Count 0 1
Partial Thromboplastin Time 1 0
Alkaline Phosphatase 0 1
Alanine Aminotransferase 0 1
Aspartate Aminotransferase 1 3
Creatinine 1 0
Hypokalemia 1 0
Hyponatremia 0 1
Phosphorous 2 1
Bilirubin 0 1
12.Secondary Outcome
Title Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs
Hide Description AEs and SAEs considered possibly, probably, or certainly related to study treatment, graded according to CTCAE Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death). SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All-Treated participants: All participants who received at least one dose of dasatinib.
Arm/Group Title Dasatinib 70 mg Dasatinib 100 mg
Hide Arm/Group Description:
Dasatinib was administered orally at 70 mg BID, for a TDD of 140 mg.
Dasatinib was administered orally at 100 mg BID, for a total daily dose (TDD) of 200 mg.
Overall Number of Participants Analyzed 23 47
Measure Type: Number
Unit of Measure: participants
Drug-related AEs 22 44
SAEs 9 11
Drug-related SAEs 6 7
Drug-related Grade 3 AEs 9 15
13.Secondary Outcome
Title Number Of Participants With Notable Drug-related AEs
Hide Description Notable drug-related AEs for dasatinib include gastrointestinal symptoms (diarrhea, nausea, vomiting and abdominal pain), fatigue, lethargy, headache, rash, fever, pleural effusion, and dyspnea.
Time Frame Continuous assessment beginning at initiation of study drug until 30 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All-Treated participants: All participants who received at least one dose of dasatinib.
Arm/Group Title Dasatinib 70 mg Dasatinib 100 mg
Hide Arm/Group Description:
Dasatinib was administered orally at 70 mg BID, for a TDD of 140 mg.
Dasatinib was administered orally at 100 mg BID, for a total daily dose (TDD) of 200 mg.
Overall Number of Participants Analyzed 23 47
Measure Type: Number
Unit of Measure: participants
Diarrhea 10 22
Nausea 8 16
Abdominal Pain 2 11
Fatigue 3 17
Rash 8 11
Pleural Effusion 9 12
Dyspnea 9 10
14.Secondary Outcome
Title Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3
Hide Description Blood samples (3 mL) were used for measurement of dasatinib plasma concentration and metabolites.
Time Frame PK assessment was performed at Week 3 visit (Day 15 ±4 days). Blood samples were obtained at Time = 0 hours, and at 1, 3 and 6 hours after each dose, and a trough sample was obtained immediately prior to any dose (~12 hours).
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants Analyzed=All Treated Participants with samples for PK analysis, n=number of participants at specified time point with samples for PK analysis
Arm/Group Title Dasatinib 70 mg Dasatinib 100 mg
Hide Arm/Group Description:
Dasatinib was administered orally at 70 mg BID, for a TDD of 140 mg.
Dasatinib was administered orally at 100 mg BID, for a total daily dose (TDD) of 200 mg.
Overall Number of Participants Analyzed 17 14
Mean (Standard Deviation)
Unit of Measure: ng/ml
Time 0 hours (100 mg, n=16; 70 mg, n=13) 10.82  (9.17) 6.96  (2.90)
Time 1 hour (100 mg, n=16; 70 mg, n=14) 107.09  (64.55) 77.21  (61.86)
Time 3 hours (100 mg, n=17; 70 mg, n=14) 58.01  (37.88) 30.21  (18.42)
Time 6 hours (100 mg, n=17; 70 mg, n=13) 23.19  (15.20) 12.64  (5.58)
Time 12 hours (100 mg, n=16; 70 mg, n=9) 11.88  (6.40) 7.41  (5.08)
15.Secondary Outcome
Title PK: Plasma Concentration of Dasatinib at Week 7 or Week 9
Hide Description Blood samples (3 mL) were used for measurement of dasatinib plasma concentration and metabolites.
Time Frame PK assessment was performed at Week 7 or 9 visit. Blood samples were obtained at Time = 0 hours, and at 1, 3 and 6 hours after each dose, and a trough sample was obtained immediately prior to any dose (~12 hours).
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Number of Participants Analyzed=All Treated Participants with samples for PK analysis, n=number of participants at specified time point with samples for PK analysis
Arm/Group Title Dasatinib 100 mg Dasatinib 70 mg Dasatinib 50 mg
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Dasatinib was administered orally at 100 mg BID, for a total daily dose (TDD) of 200 mg.
Dasatinib was administered orally at 70 mg BID, for a TDD of 140 mg.
Dasatinib was administered orally at a starting dose of 70 mg BID. Dose adjustment was made according to tolerance, with reduction to 50 mg BID. Participants continued study treatment until PD or unacceptable toxicity. Dasatinib dose was adjusted so that drug-related toxicities were either Grade 0 - 1 or were Grade 2 toxicities that were adequately managed with outpatient therapy or deemed clinically acceptable.
Overall Number of Participants Analyzed 5 9 1
Mean (Standard Deviation)
Unit of Measure: ng/ml
Time 0 hours (100 mg, n=5; 70 mg, n=7; 50 mg, n=1) 9.49  (4.94) 6.62  (3.54) 6.06  (0.00)
Time 1 hour (100 mg, n=5; 70 mg, n=8; 50 mg, n=1) 131.09  (57.52) 49.28  (37.97) 4.75  (0.00)
Time 3 hours (100 mg, n=5; 70 mg, n=9; 50 mg, n=1) 55.26  (23.65) 42.27  (21.94) 35.74  (0.00)
Time 6 hours (100 mg, n=5; 70 mg, n=8; 50 mg, n=1) 23.58  (8.65) 13.03  (3.34) 35.91  (0.00)
Time 12 hours (100 mg, n=4; 70 mg, n=6; 50 mg, n=1 10.52  (3.55) 5.00  (2.26) 9.02  (0.00)
16.Secondary Outcome
Title Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 3 in Participants With and Without DCR
Hide Description Collagen Type IV is a circulating marker related to the modulation of the vascular endothelial growth factor (VEGF)-pathway. An assay of Collagen Type IV in plasma was performed by ELISA.
Time Frame At Baseline and Week 3 of treatment (Day 15 ±4 days)
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Number of Participants Analyzed=All Treated Participants with samples for PD analysis, n=number of participants at specified time point with samples for PD analysis
Arm/Group Title Dasatinib 70 mg Dasatinib 100 mg
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Dasatinib was administered orally at 70 mg BID, for a TDD of 140 mg.
Dasatinib was administered orally at 100 mg BID, for a total daily dose (TDD) of 200 mg.
Overall Number of Participants Analyzed 29 19
Mean (90% Confidence Interval)
Unit of Measure: percent change
Participants with no DCR (n=27, n=16)
32.07
(23.58 to 41.15)
35.92
(25.72 to 46.94)
Participants with DCR (n=2, n=3)
22.01
(11.21 to 33.87)
40.74
(10.81 to 78.75)
All Participants (n=29, n=19)
31.35
(23.46 to 39.76)
36.67
(27.74 to 46.21)
17.Secondary Outcome
Title Pharmacodynamics: Percent Change From Baseline In Plasma Level of Collagen Type IV at Week 5 in Participants With and Without DCR
Hide Description Collagen Type IV is a circulating marker related to the modulation of the vascular endothelial growth factor (VEGF)-pathway. An assay of Collagen Type IV in plasma was performed by ELISA.
Time Frame Week 5
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Hide Analysis Population Description
Number of Participants Analyzed=All Treated Participants with samples for PD analysis, n=number of participants at specified time point with samples for PD analysis
Arm/Group Title Dasatinib 70 mg Dasatinib 100 mg
Hide Arm/Group Description:
Dasatinib was administered orally at 70 mg BID, for a TDD of 140 mg.
Dasatinib was administered orally at 100 mg BID, for a total daily dose (TDD) of 200 mg.
Overall Number of Participants Analyzed 23 15
Mean (90% Confidence Interval)
Unit of Measure: percent change
Participants with no DCR (n=20, n=12)
45.37
(33.43 to 58.38)
28.45
(-2.25 to 68.80)
Participants with DCR (n=3, n=3)
17.13
(-11.57 to 55.14)
64.51
(34.18 to 101.68)
All Participants (n=23, n=15)
41.33
(30.41 to 53.18)
34.97
(8.48 to 67.92)
18.Secondary Outcome
Title Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 3 in Participants With and Without DCR
Hide Description VEGF-stimulated disruption of the cadherin-catenin complex leads to tumor cell invasion and metastasis. VEGFR2 plasma levels were assayed by ELISA as a marker of VEGF pathway modulation.
Time Frame At Baseline and Week 3 of treatment (Day 15 ±4 days)
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Hide Analysis Population Description
Number of Participants Analyzed=All Treated Participants with samples for PD analysis, n=number of participants at specified time point with samples for PD analysis
Arm/Group Title Dasatinib 70 mg Dasatinib 100 mg
Hide Arm/Group Description:
Dasatinib was administered orally at 70 mg BID, for a TDD of 140 mg.
Dasatinib was administered orally at 100 mg BID, for a total daily dose (TDD) of 200 mg.
Overall Number of Participants Analyzed 29 15
Mean (90% Confidence Interval)
Unit of Measure: percent change
Participants with no DCR (n=27, n=16)
21.88
(15.98 to 28.08)
23.61
(20.41 to 27.17)
Participants with DCR (n=2, n=3)
14.77
(6.25 to 23.97)
-5.03
(-55.67 to 103.43)
All Participants (n=29, n=19)
21.37
(15.88 to 27.13)
18.57
(9.95 to 27.86)
19.Secondary Outcome
Title Pharmacodynamics: Percent Change From Baseline In Plasma Level of VEGFR2 at Week 5 in Participants With and Without DCR
Hide Description VEGF-stimulated disruption of the cadherin-catenin complex leads to tumor cell invasion and metastasis. VEGFR2 plasma levels were assayed by ELISA as a marker of VEGF pathway modulation.
Time Frame At Baseline and Week 5 of treatment
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Hide Analysis Population Description
Number of Participants Analyzed=All Treated Participants with samples for PD analysis, n=number of participants at specified time point with samples for PD analysis
Arm/Group Title Dasatinib 70 mg Dasatinib 100 mg
Hide Arm/Group Description:
Dasatinib was administered orally at 70 mg BID, for a TDD of 140 mg.
Dasatinib was administered orally at 100 mg BID, for a total daily dose (TDD) of 200 mg.
Overall Number of Participants Analyzed 23 15
Mean (90% Confidence Interval)
Unit of Measure: percent change
Participants with no DCR (n=20, n=12)
27.23
(22.53 to 32.10)
26.36
(20.85 to 32.13)
Participants with DCR (n=3, n=3)
16.46
(8.27 to 25.27)
37.25
(23.08 to 53.05)
All Participants (n=23, n=15)
25.77
(21.51 to 30.18)
28.47
(23.48 to 33.66)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Dasatinib
Hide Arm/Group Description Dasatinib was administered orally at 70 mg BID (TDD=140 mg) or 100 mg BID (TDD=200 mg).
All-Cause Mortality
Dasatinib
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Dasatinib
Affected / at Risk (%)
Total   20/70 (28.57%) 
Gastrointestinal disorders   
NAUSEA  1  2/70 (2.86%) 
VOMITING  1  1/70 (1.43%) 
DIARRHOEA  1  2/70 (2.86%) 
ABDOMINAL PAIN  1  1/70 (1.43%) 
ABDOMINAL PAIN LOWER  1  1/70 (1.43%) 
General disorders   
FATIGUE  1  2/70 (2.86%) 
PYREXIA  1  1/70 (1.43%) 
OEDEMA PERIPHERAL  1  1/70 (1.43%) 
GENERAL PHYSICAL HEALTH DETERIORATION  1  3/70 (4.29%) 
Infections and infestations   
PNEUMONIA  1  1/70 (1.43%) 
SINUSITIS  1  1/70 (1.43%) 
LOBAR PNEUMONIA  1  1/70 (1.43%) 
Injury, poisoning and procedural complications   
FALL  1  1/70 (1.43%) 
TOOTH INJURY  1  1/70 (1.43%) 
Investigations   
WEIGHT INCREASED  1  1/70 (1.43%) 
Metabolism and nutrition disorders   
DEHYDRATION  1  1/70 (1.43%) 
FLUID RETENTION  1  1/70 (1.43%) 
Musculoskeletal and connective tissue disorders   
BACK PAIN  1  1/70 (1.43%) 
MUSCULOSKELETAL PAIN  1  1/70 (1.43%) 
MUSCULOSKELETAL CHEST PAIN  1  1/70 (1.43%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
MALIGNANT NEOPLASM PROGRESSION  1  1/70 (1.43%) 
Nervous system disorders   
HEADACHE  1  2/70 (2.86%) 
HEMIPARESIS  1  1/70 (1.43%) 
BRAIN OEDEMA  1  1/70 (1.43%) 
Renal and urinary disorders   
RENAL FAILURE ACUTE  1  1/70 (1.43%) 
Respiratory, thoracic and mediastinal disorders   
DYSPNOEA  1  3/70 (4.29%) 
PLEURAL EFFUSION  1  5/70 (7.14%) 
PRODUCTIVE COUGH  1  1/70 (1.43%) 
PULMONARY EMBOLISM  1  1/70 (1.43%) 
Skin and subcutaneous tissue disorders   
SWELLING FACE  1  1/70 (1.43%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dasatinib
Affected / at Risk (%)
Total   65/70 (92.86%) 
Blood and lymphatic system disorders   
ANAEMIA  1  6/70 (8.57%) 
Cardiac disorders   
PERICARDIAL EFFUSION  1  7/70 (10.00%) 
Eye disorders   
LACRIMATION INCREASED  1  4/70 (5.71%) 
Gastrointestinal disorders   
NAUSEA  1  26/70 (37.14%) 
VOMITING  1  17/70 (24.29%) 
DIARRHOEA  1  34/70 (48.57%) 
DYSPEPSIA  1  4/70 (5.71%) 
CONSTIPATION  1  7/70 (10.00%) 
ABDOMINAL PAIN  1  15/70 (21.43%) 
ABDOMINAL DISTENSION  1  4/70 (5.71%) 
ABDOMINAL PAIN UPPER  1  9/70 (12.86%) 
General disorders   
CHILLS  1  6/70 (8.57%) 
FATIGUE  1  19/70 (27.14%) 
PYREXIA  1  14/70 (20.00%) 
ASTHENIA  1  24/70 (34.29%) 
CHEST PAIN  1  5/70 (7.14%) 
Investigations   
WEIGHT DECREASED  1  8/70 (11.43%) 
HAEMOGLOBIN DECREASED  1  4/70 (5.71%) 
ALANINE AMINOTRANSFERASE  1  5/70 (7.14%) 
ASPARTATE AMINOTRANSFERASE  1  4/70 (5.71%) 
ALANINE AMINOTRANSFERASE INCREASED  1  10/70 (14.29%) 
ASPARTATE AMINOTRANSFERASE INCREASED  1  12/70 (17.14%) 
BLOOD ALKALINE PHOSPHATASE INCREASED  1  6/70 (8.57%) 
Metabolism and nutrition disorders   
ANOREXIA  1  17/70 (24.29%) 
Musculoskeletal and connective tissue disorders   
MYALGIA  1  6/70 (8.57%) 
BACK PAIN  1  5/70 (7.14%) 
ARTHRALGIA  1  10/70 (14.29%) 
MUSCULOSKELETAL CHEST PAIN  1  5/70 (7.14%) 
Nervous system disorders   
HEADACHE  1  28/70 (40.00%) 
DIZZINESS  1  5/70 (7.14%) 
Psychiatric disorders   
INSOMNIA  1  4/70 (5.71%) 
Respiratory, thoracic and mediastinal disorders   
COUGH  1  11/70 (15.71%) 
DYSPNOEA  1  24/70 (34.29%) 
PLEURAL EFFUSION  1  19/70 (27.14%) 
Skin and subcutaneous tissue disorders   
RASH  1  19/70 (27.14%) 
ALOPECIA  1  4/70 (5.71%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
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Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
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Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00371345     History of Changes
Other Study ID Numbers: CA180-088
First Submitted: September 1, 2006
First Posted: September 4, 2006
Results First Submitted: October 6, 2010
Results First Posted: November 5, 2010
Last Update Posted: April 26, 2011