Phase I Study of Dasatinib (BMS-354825) and Capecitabine for Women With Advanced Breast Cancer
- Registration Number
- NCT00452673
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 52
- Female with advanced breast cancer previously treated with a taxane and an anthracycline
- No pleural or pericardial effusion
- Not receiving anticoagulants
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 50 mg BID dasatinib + 825 mg/m^2 BID capecitabine Dasatinib Twice a day (BID) for 2 weeks of a 3-week cycle 50 mg BID dasatinib + 825 mg/m^2 BID capecitabine Capecitabine Twice a day (BID) for 2 weeks of a 3-week cycle 70 mg BID dasatinib + 825 mg/m^2 BID capecitabine Dasatinib BID for 2 weeks of a 3-week cycle 70 mg BID dasatinib + 825 mg/m^2 BID capecitabine Capecitabine BID for 2 weeks of a 3-week cycle 70 mg BID dasatinib + 1000 mg/m^2 BID capecitabine Dasatinib BID for 2 weeks of a 3-week cycle 70 mg BID dasatinib + 1000 mg/m^2 BID capecitabine Capecitabine BID for 2 weeks of a 3-week cycle 100 mg QD dasatinib + 1000 mg/m^2 BID capecitabine Capecitabine 2 weeks of a 3-week cycle 100 mg QD dasatinib + 1000 mg/m^2 BID capecitabine Dasatinib 2 weeks of a 3-week cycle
- Primary Outcome Measures
Name Time Method Number of Participants With Dose Limiting Toxicities Per Dose Level - Safety Population Day 1 to 30 days post last dose 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.
- Secondary Outcome Measures
Name Time Method Number of Participants With Overall Response to Tumor - Efficacy Evaluable Population Day 1 to 30 days post last dose 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.
Number of Participants With Deaths, Serious Adverse Events, Adverse Events, Adverse Events Leading to Discontinuation and Treatment-related Adverse Events - Safety Population Day 1 up to 30 days post last dose 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 On-study With Grade 3 - 4 Chemistry Laboratory Values in Those Participants With a Baseline Laboratory Value of Grade 0 - Safety Population Day 1 to 30 days post last dose 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.
Objective Response Rate (ORR) and Disease Control Rate - Efficacy Evaluable Population Day 1 up to 30 days post last dose 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 Day 1 up to 30 days post last dose 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.
Trial Locations
- Locations (5)
Local Institution
🇪🇸Sevilla, Spain
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
City Of Hope National Medical Center
🇺🇸Duarte, California, United States
New York Presbyterian Hospital
🇺🇸New York, New York, United States
Northwestern University Feinberg School Of Medicine
🇺🇸Chicago, Illinois, United States