RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This randomized phase II trial is studying two different schedules of dasatinib to compare how well they work in treating patients with stage IV breast cancer that has spread to the bone.
OBJECTIVES: * Compare the progression-free survival of patients with stage IV bone metastasis-predominant breast cancer treated with 1 of 2 treatment schedules of dasatinib. * Compare the response rate (complete and partial, confirmed and unconfirmed) in patients treated with these regimens. * Compare the MUC-1 antigen response rate (CA 15-3 or CA 27-29) in patients treated with these regimens. * Compare the circulating tumor cell response rate in patients treated with these regimens. * Compare the anti-osteoclast activity, as measured by changes in bone turnover markers, in patients treated with these regimens. * Compare the frequency and severity of toxicities of these regimens in these patients. * Compare the pain profiles of these patients and explore changes over time. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to concurrent trastuzumab (Herceptin®) treatment (yes vs no). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral dasatinib once daily. * Arm II: Patients receive oral dasatinib twice daily. In both treatment arms, treatment continues for at least 24 weeks in the absence of disease progression or unacceptable toxicity. Blood samples are acquired from patients once weekly in weeks 1, 4, 8, 16, and 24. Samples are analyzed for tumor markers, circulating tumor cells, and bone markers. Patients complete a self-reported brief pain inventory questionnaire at baseline and once in weeks 8, 16, and 24. After completion of study treatment, patients are followed every 3-6 months for up to 2 years. PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
85
given orally
Progression-free Survival
RECIST progression defined as 20% increase in the sum of longest diameters of target measurable lesions over the smallest sum observed, unequivocal progression of non-measurable disease, the appearance of any new lesion/site, death due to disease without prior documentation of progression and without symptomatic deterioration, development of one or more new bone lesions from baseline, or symptomatic deterioration related to disease progression. Time from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at last date of contact.
Time frame: Up to 2 years
Response Rate (Complete and Partial, Confirmed and Unconfirmed)
Complete Response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions, no disease related symptoms, normalization of markers and other abnormal lab values. Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration. Progression is 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed, unequivocal progression of non-measurable disease, appearance of any new lesion/site, death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.
Time frame: Up to 2 years
MUC-1 Antigen Response
MUC-1 Complete Response is reduction in MUC-1 such that MUC-1 \<= ULN. MUC-1 Partial Response is greater than or equal to a 50% reduction in MUC-1 from baseline, but not qualifying as a CR. MUC-1 Progression is greater than or equal to a 50% increase in MUC-1 from baseline. MUC-1 Stable Disease is MUC-1 response not qualifying as CR, PR, or Progression.
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Providence Cancer Center at Providence Hospital
Mobile, Alabama, United States
Alaska Regional Hospital Cancer Center
Anchorage, Alaska, United States
Providence Cancer Center
Anchorage, Alaska, United States
Highlands Oncology Group - Springdale
Bentonville, Arkansas, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
East Bay Radiation Oncology Center
Castro Valley, California, United States
Eden Medical Center
Castro Valley, California, United States
Valley Medical Oncology Consultants - Castro Valley
Castro Valley, California, United States
Valley Medical Oncology
Fremont, California, United States
Contra Costa Regional Medical Center
Martinez, California, United States
...and 107 more locations
Time frame: at 4, 8, 16, and 24 weeks
Circulating Tumor Cells (CTC) Response Rate
CTC response at 4 weeks is defined as the number of patients with initially elevated CTCs (\>= 5 cells/7.5 ml), whose CTC level drops to \< 5.
Time frame: Up to 4 weeks
Change in Serum Bone Turnover Markers Over Time -- NTx
Analysis included mean values of the serum biomarker NTx at baseline, 4, and 8 weeks.
Time frame: at baseline, 4, and 8 weeks
Change in Serum Bone Turnover Markers Over Time -- BAP
Analysis included mean values of the serum biomarker BAP at baseline, 4, and 8 weeks.
Time frame: at baseline, 4, and 8 weeks
Change in Serum Bone Turnover Markers Over Time
Analysis included mean values of the serum biomarkers sRANKL, IL-6, DKK, VEGF at baseline, 4, and 8 weeks.
Time frame: at baseline, 4, and 8 weeks
Change in Serum Bone Turnover Markers Over Time -- OC
Analysis included mean values of the serum biomarker OC at baseline, 4, and 8 weeks.
Time frame: at baseline, 4, and 8 weeks
Change in Serum Bone Turnover Markers Over Time -- OPG
Analysis included mean values of the serum biomarker OPG at baseline, 4, and 8 weeks.
Time frame: at baseline, 4, and 8 weeks
Change in Serum Bone Turnover Markers Over Time -- TRAP
Analysis included mean values of the serum biomarker TRAP at baseline, 4, and 8 weeks.
Time frame: at baseline, 4, and 8 weeks
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Up to 2 years
Mean Patient-reported Pain
Patient's rating of "worst pain" experienced between prestudy and week 24. Changes of \>=2 points on the Brief Pain Inventory (BPI) are of interest. Pain is self-reported on the Brief Pain Inventory Short Form, on a 0-10 response scale, with higher scores reflecting more pain and more interference with functioning.
Time frame: Baseline, 8, 16, and 24 weeks