Phase I Study of Dasatinib (BMS-354825) and Capecitabine for Women With Advanced Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to learn about the safety and efficacy of Dasatinib in combination with Capecitabine for patients with advanced breast cancer, and who have received treatment with a taxane and an anthracycline

Official Title
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Phase I Study of Dasatinib (BMS-354825) and Capecitabine for Advanced Breast Cancer

Conditions
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Advanced Breast Cancer

Intervention / Treatment
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* Drug: Dasatinib
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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For additional information, please contact the BMS oncology clinical trial information service at 855-216-0126 or email MyCancerStudyConnect@emergingmed.com. Please visit www.BMSStudyConnect.com for more information on clinical trial participation. Inclusion Criteria: Female with advanced breast cancer previously treated with a taxane and an anthracycline No pleural or pericardial effusion Not receiving anticoagulants

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg BID dasatinib + 825 mg/m^2 BID capecitabine<br>Twice a day (BID) for 2 weeks of a 3-week cycle | Drug: Dasatinib<br>* Tablets, Oral, 50 mg or 70 mg twice a day (BID), 100 mg once per day (QD). Treatment may continue until disease progression<br>* Other names: BMS-354825;Drug: Capecitabine<br>* Tablets, Oral, 660 - 1250 mg/m^2 twice a day (BID). Treatment may continue until disease progression.<br>* Other names: Spycel®;|
| Experimental: 70 mg BID dasatinib + 825 mg/m^2 BID capecitabine<br>BID for 2 weeks of a 3-week cycle | Drug: Dasatinib<br>* Tablets, Oral, 50 mg or 70 mg twice a day (BID), 100 mg once per day (QD). Treatment may continue until disease progression<br>* Other names: BMS-354825;Drug: Capecitabine<br>* Tablets, Oral, 660 - 1250 mg/m^2 twice a day (BID). Treatment may continue until disease progression.<br>* Other names: Spycel®;|
| Experimental: 70 mg BID dasatinib + 1000 mg/m^2 BID capecitabine<br>BID for 2 weeks of a 3-week cycle | Drug: Dasatinib<br>* Tablets, Oral, 50 mg or 70 mg twice a day (BID), 100 mg once per day (QD). Treatment may continue until disease progression<br>* Other names: BMS-354825;Drug: Capecitabine<br>* Tablets, Oral, 660 - 1250 mg/m^2 twice a day (BID). Treatment may continue until disease progression.<br>* Other names: Spycel®;|
| Experimental: 100 mg QD dasatinib + 1000 mg/m^2 BID capecitabine<br>2 weeks of a 3-week cycle | Drug: Dasatinib<br>* Tablets, Oral, 50 mg or 70 mg twice a day (BID), 100 mg once per day (QD). Treatment may continue until disease progression<br>* Other names: BMS-354825;Drug: Capecitabine<br>* Tablets, Oral, 660 - 1250 mg/m^2 twice a day (BID). Treatment may continue until disease progression.<br>* Other names: Spycel®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities Per Dose Level - Safety Population | Safety was assessed from first dose of study drug through at least 30 days after the last dose, until resolution of drug-related toxicity or when toxicity was deemed irreversible, whichever was longer. An adverse event (AE) was considered a dose limiting toxicity (DLT) if it occurred in the first 21 days and was at least possibly related to study drugs and were: Clinically-evident toxicity of Grade >= 3, or of Grade 2 which required interruption of treatment for >= 7 days (consecutive or non-consecutive); non-hematologic abnormal laboratory value of Grade >= 3, or hematologic toxicity of Grade 4, which persisted 7 days; any grade toxicity which in the judgment of the investigator required a dose reduction or removal from further study therapy. | Day 1 to 30 days post last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Deaths, Serious Adverse Events, Adverse Events, Adverse Events Leading to Discontinuation and Treatment-related Adverse Events - Safety Population | Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious AE (SAE)=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. | Day 1 up to 30 days post last dose | 
| Number of Participants With Overall Response to Tumor - Efficacy Evaluable Population | Complete Response (CR): disappearance of all target and non-target lesions, with confirmation at >=4 weeks interval; Partial Response (PR): >= 30% decrease in sum of longest diameter (LDs) of target lesions, taking as reference the baseline sum LD, with confirmation at >= 4 weeks interval. Progressive Disease (PD): Appearance of new lesion(s), or >=20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions. Stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, without unequivocal progression of non-target lesions, after >=6 weeks on study. Radiological tumor assessment by computed tomography (CT) or magnetic resonance imaging (MRI) occurred every 6 weeks. For those patients who were on treatment > 24 weeks, the tumor assessment occurred every 9 weeks. | Day 1 to 30 days post last dose | 
| Objective Response Rate (ORR) and Disease Control Rate - Efficacy Evaluable Population | Objective response rate was the percentage of participants, (n/N; number with objective response per Number evaluated) whose best response is either a Complete Response (CR) or a Partial Response (PR). Disease control rate was defined as percentage (n/N) of participants with stable disease greater than (>) 6 months, PR, or CR. Efficacy Evaluable Population: All participants with at least one measurable lesion at baseline, who received at least one dose of combination study drug and have at least one on-study tumor assessment or stopped study treatment prior to first assessment, were evaluated. Those who stop treatment prior to tumor assessment for reasons unrelated to disease or drug were excluded. | Day 1 up to 30 days post last dose | 
| Number of Participants On-Study With Grade 3 - 4 Hematology Laboratory Test Values in Those Participants With a Baseline Laboratory Value of Grade 0 - Safety Population | National Cancer Institute Common terminology criteria (CTC), Version 3 used to assess parameters. Lower limit of normal (LLN). CTC criteria: Absolute neutrophil count (ANC). Leukocytes (White blood cells) Grade (Gr) 1:<LLN to 3.0*10^9/L, Gr 2:<3.0 to 2.0*10^9/L, Gr 3:<2.0 to 1.0*10^9/L, Gr 4:<1.0*10^9/L. ANC Gr 1:<LLN to 1.5*10^9/L, Gr 2:<1.5 to 1.0*10^9/L, Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 1:LLN to 75.0*10^9/L, Gr 2:<75.0 to 50.0*10^9/L, Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL. Participants with a baseline hematology lab value of Gr 0 but who had Gr 3 - 4 hematology value while on-study are presented below. | Day 1 up to 30 days post last dose | 
| Number of Participants On-study With Grade 3 - 4 Chemistry Laboratory Values in Those Participants With a Baseline Laboratory Value of Grade 0 - Safety Population | CTC, Version 3 used to assess parameters. (ULN)=upper limit of normal: (ALT)= alanine transaminase; (AST)=aspartate aminotransferase; (ALP)=alkaline phosphatase. ALT Grade (Gr)1:>ULN to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. AST Gr 1: >ULN to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Total bilirubin Gr 1: >ULN to 1.5*ULN; Gr 2: >1.5 to 3.0*ULN; Gr 3: >3.0 to 10.0*ULN; Gr 4: >10.0*ULN. ALP (U/L) Gr1:>ULN to 2.5*ULN, Gr2:>2.5 to 5.0*ULN, Gr3:>5.0 to 20.0*ULN, Gr4:>20.0*ULN. Albumin (low) Gr 1:<LLN - 3 grams per deciliter (g/dL)to <LLN - 3 g/dL; Gr 2: <3 - 2 g/dL to < 3.0 - 2.0 g/dL; Gr 3: < 2 g/dL to <2 g/L. Participants with a baseline chemistry lab value of Gr 0 but who had Gr 3 - 4 chemistry value while on-study are presented below. | Day 1 to 30 days post last dose |