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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00452673
First received: March 26, 2007
Last updated: December 5, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Advanced Breast Cancer
Drug: Dasatinib
Drug: Capecitabine
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 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.

  • 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. 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.


Enrollment: 52
Study Start Date: June 2007
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 50 mg BID dasatinib + 825 mg/m^2 BID capecitabine
Twice a day (BID) for 2 weeks of a 3-week cycle
Drug: Dasatinib
Tablets, Oral, 50 mg or 70 mg twice a day (BID), 100 mg once per day (QD). Treatment may continue until disease progression
Other Name: BMS-354825
Drug: Capecitabine
Tablets, Oral, 660 - 1250 mg/m^2 twice a day (BID). Treatment may continue until disease progression.
Other Name: Spycel®
Experimental: 70 mg BID dasatinib + 825 mg/m^2 BID capecitabine
BID for 2 weeks of a 3-week cycle
Drug: Dasatinib
Tablets, Oral, 50 mg or 70 mg twice a day (BID), 100 mg once per day (QD). Treatment may continue until disease progression
Other Name: BMS-354825
Drug: Capecitabine
Tablets, Oral, 660 - 1250 mg/m^2 twice a day (BID). Treatment may continue until disease progression.
Other Name: Spycel®
Experimental: 70 mg BID dasatinib + 1000 mg/m^2 BID capecitabine
BID for 2 weeks of a 3-week cycle
Drug: Dasatinib
Tablets, Oral, 50 mg or 70 mg twice a day (BID), 100 mg once per day (QD). Treatment may continue until disease progression
Other Name: BMS-354825
Drug: Capecitabine
Tablets, Oral, 660 - 1250 mg/m^2 twice a day (BID). Treatment may continue until disease progression.
Other Name: Spycel®
Experimental: 100 mg QD dasatinib + 1000 mg/m^2 BID capecitabine
2 weeks of a 3-week cycle
Drug: Dasatinib
Tablets, Oral, 50 mg or 70 mg twice a day (BID), 100 mg once per day (QD). Treatment may continue until disease progression
Other Name: BMS-354825
Drug: Capecitabine
Tablets, Oral, 660 - 1250 mg/m^2 twice a day (BID). Treatment may continue until disease progression.
Other Name: Spycel®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00452673

Locations
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
Italy
Local Institution
Rozzano, Milano, Italy, 20089
Spain
Local Institution
Barcelona, Spain, 08035
Local Institution
Sevilla, Spain, 41013
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00452673     History of Changes
Other Study ID Numbers: CA180-004, EUDRACT: 2006-006973-26
Study First Received: March 26, 2007
Results First Received: October 9, 2013
Last Updated: December 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Capecitabine
Fluorouracil
Dasatinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 14, 2014