Phase I Study of Dasatinib (BMS-354825) and Capecitabine for Women With Advanced Breast Cancer
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
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Dasatinib (BMS-354825) and Capecitabine for Advanced Breast Cancer|
- Number of Participants With Dose Limiting Toxicities Per Dose Level - Safety Population [ Time Frame: Day 1 to 30 days post last dose ] [ Designated as safety issue: Yes ]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.
- Number of Participants With Deaths, Serious Adverse Events, Adverse Events, Adverse Events Leading to Discontinuation and Treatment-related Adverse Events - Safety Population [ Time Frame: Day 1 up to 30 days post last dose ] [ Designated as safety issue: Yes ]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.
- Number of Participants With Overall Response to Tumor - Efficacy Evaluable Population [ Time Frame: Day 1 to 30 days post last dose ] [ Designated as safety issue: No ]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.
- Objective Response Rate (ORR) and Disease Control Rate - Efficacy Evaluable Population [ Time Frame: Day 1 up to 30 days post last dose ] [ Designated as safety issue: No ]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.
- 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 [ Time Frame: Day 1 up to 30 days post last dose ] [ Designated as safety issue: Yes ]National Cancer Institute Commom terminology criteria (CTC), Version 3 used to assess parameters. LLN=lower limit of normal. CTC criteria: ANC=absolute neutrophil count. 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.
- 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 [ Time Frame: Day 1 to 30 days post last dose ] [ Designated as safety issue: Yes ]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. ALK (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.
|Study Start Date:||June 2007|
|Study Completion Date:||October 2012|
|Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
Drug: Dasatinib + Capecitabine
Tablets, Oral, 50-100 mg. + 660-1250 mg/M2, twice daily, treatment may continue until disease progression
|United States, California|
|City Of Hope National Medical Center|
|Duarte, California, United States, 91010-3000|
|United States, Illinois|
|Northwestern University Feinberg School Of Medicine|
|Chicago, Illinois, United States, 60611|
|United States, New York|
|New York Presbyterian Hospital|
|New York, New York, United States, 10065|
|United States, Washington|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109-1023|
|Rozzano, Milano, Italy, 20089|
|Barcelona, Spain, 08035|
|Sevilla, Spain, 41013|
|Study Director:||Bristol-Myers Squibb||Bristol-Myers Squibb|