Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Recurrence

Breast Neoplasms

Neoplasm Metastasis

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Estrogens

Mitogens

Dasatinib

Progesterone

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants with either a Human epidermal growth factor (Her2/neu)-amplified tumor type or ER and/or PgR positive tumor types received oral dasatinib twice daily (BID).

Tablets, Oral, 70 mg, twice daily, as long as the participant benefits (average \<6 months)

Tablets, Oral, 100mg, twice daily, as long as the participant benefits (average \<6 months)

Dasatinib 100 mg

Bristol-Myers Squibb

This study will determine whether the investigational drug dasatinib is effective in treatment of women with progressive advanced ER+/PR+ or Her2/neu+ breast cancer

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

Phase II Study of Dasatinib (BMS-354825) for Advanced Estrogen/Progesterone Receptor-Positive or Her2/Neu-Positive Breast Cancer

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.

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.

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.

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.

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.

PFS was defined as time from first dosing date until the first date that Progressive Disease (PD) was observed.

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.

PFS was defined as time from first dosing date until the first date that progressive disease (PD) was observed.

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.

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.

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.

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.

Notable drug-related AEs for dasatinib include gastrointestinal symptoms (diarrhea, nausea, vomiting and abdominal pain), fatigue, lethargy, headache, rash, fever, pleural effusion, and dyspnea.

Blood samples (3 mL) were used for measurement of dasatinib plasma concentration and metabolites.

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.

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.

Study Director

Dasatinib was administered orally at 70 mg BID (TDD=140 mg) or 100 mg BID (TDD=200 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.

Her2/Neu-amplified Tumor Type

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.

ER and/or PgR Positive Tumor Type

Total

Age Continuous

<=50 years

>=50 years

Age, Customized

Sex: Female, Male

France

United States

Argentina

Spain

Belgium

Peru

Italy

Region of Enrollment

BMS Study Director

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.

Her2/Neu-amplified Tumor, 70 mg Twice Daily (BID) Dasatinib

Her2/Neu-amplified Tumor, 100 mg BID

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.

ER and/or PgR Positive Tumor, 70 mg BID Dasatinib

ER and/or PgR Positive Tumor, 100 mg BID Dasatinib

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).

Number of Participants With Objective Response

Her2/Neu-amplified Tumor, 100 mg BID Dasatinib

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).

All Response-evaluable Participants

Percentage of Participants With Objective Response

Participants with CR

Participants with unconfirmed PR (uCR)

Participants with PR

Participants with SD ≥16 weeks

Total Participants with DCR

Number of Response-evaluable Participants With Disease Control (DCR)

Percentage of Response-evaluable Participants With Disease Control (DCR)

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).

Her2/Neu-amplified Tumor

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).

ER and/or PgR Positive Tumor

All Participants

All-Treated subjects: All subjects who received at least one dose of dasatinib. The longest on-study observation for a participant was 45 weeks.

Number of Participants Who Progressed

Median Progression Free Survival (PFS)

Week 9

Week 17

Week 25

Percentage of Participants With Progression-free Survival (PFS) at Weeks 9, 17, and 25

Participant with Human epidermal growth factor (Her2/neu)-amplified tumor type (also positive for ER and PgR) who received 100 mg dasatinib BID.

Participant CA180088-18-88009, HER-2 Group

Participant with ER and PgR-amplified tumor type who received 100 mg dasatinib BID

Participant CA180088-16-88002, ER and/or PgR Group

Participant with ER and PgR-amplified tumor type who received 70 mg dasatinib BID

Participant CA180088-29-88085, ER and/or PgR Group

Of 69 response-evaluable participants, three had an objective response of PR.

Duration Of Objective Response

All Deaths

All AEs

AEs Leading to Discontinuation

Dasatinib was administered orally at 70 mg BID, for a TDD of 140 mg.

Dasatinib 70 mg

Dasatinib was administered orally at 100 mg BID, for a total daily dose (TDD) of 200 mg.

All-Treated participants: All participants who received at least one dose of dasatinib.

Number of Participants With Death, Adverse Events (AEs), and AEs Leading to Discontinuation

Granulocytes

Hemoglobin

Platelet Count

Partial Thromboplastin Time

Alkaline Phosphatase

Alanine Aminotransferase

Aspartate Aminotransferase

Creatinine

Hypokalemia

Hyponatremia

Phosphorous

Bilirubin

Number of Participants With On-study CTCAE Version 3.0 Grade 3-4 Laboratory Abnormalities

Drug-related AEs

SAEs

Drug-related SAEs

Drug-related Grade 3 AEs

Number of Participants With Serious AEs (SAEs), Drug-related AEs, Drug-related SAEs, and Drug-Related Grade 3 AEs

Diarrhea

Nausea

Abdominal Pain

Fatigue

Rash

Pleural Effusion

Dyspnea

Number Of Participants With Notable Drug-related AEs

Time 0 hours (100 mg, n=16; 70 mg, n=13)

Time 1 hour (100 mg, n=16; 70 mg, n=14)

Time 3 hours (100 mg, n=17; 70 mg, n=14)

Time 6 hours (100 mg, n=17; 70 mg, n=13)

Time 12 hours (100 mg, n=16; 70 mg, n=9)

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

Pharmacokinetics (PK): Plasma Concentration of Dasatinib at Week 3

Time 0 hours (100 mg, n=5; 70 mg, n=7; 50 mg, n=1)

Time 1 hour (100 mg, n=5; 70 mg, n=8; 50 mg, n=1)

Time 3 hours (100 mg, n=5; 70 mg, n=9; 50 mg, n=1)

Time 6 hours (100 mg, n=5; 70 mg, n=8; 50 mg, n=1)

Time 12 hours (100 mg, n=4; 70 mg, n=6; 50 mg, n=1

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.

Dasatinib 50 mg

PK: Plasma Concentration of Dasatinib at Week 7 or Week 9

Participants with no DCR (n=27, n=16)

Participants with DCR (n=2, n=3)

All Participants (n=29, n=19)

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

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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