S0622, Dasatinib in Treating Patients With Stage IV Breast Cancer That Has Spread to the Bone
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Studies of Two Different Schedules of Dasatinib (NSC-732517) in Bone Metastasis Predominant Metastatic Breast Cancer|
- Progression-free survival, with disease progression defined as an increase in measurable disease, the appearance of new lesions, and/or clinical deterioration related to disease progression [ Time Frame: Disease assessed every 8 weeks for up to 2 years until progression. ] [ Designated as safety issue: No ]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.
- MUC-1 antigen response [ Time Frame: at 4, 8, 16, and 24 weeks ] [ Designated as safety issue: No ]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. MUC-1 Inadequate Assessment, response unknown: MUC-1 response has not been adequately assessed.
- Change in serum bone turnover markers over time [ Time Frame: at 4, 8, 16, and 24 weeks ] [ Designated as safety issue: No ]
- Circulating tumor cell (CTC) response [ Time Frame: at 4, 8, 16, and 24 weeks ] [ Designated as safety issue: No ]CTC Response: CTC < 5 cells / 7.5 mL; CTC Non-Response: CTC ≥ 5 cells / 7.5 mL; CTC Inadequate Assessment, response: CTC not able to be evaluated.
- Toxicity [ Time Frame: Patients assessed at least every eight weeks while on protocol treatment, for up to 2 years ] [ Designated as safety issue: Yes ]Only adverse events that are possibly, probably or definitely related to study drug are reported.
- Response rate (complete and partial, confirmed and unconfirmed) [ Time Frame: Patients assessed at least every eight weeks while on protocol treatment, for up to 2 years ] [ Designated as safety issue: No ]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 and/or unequivocal progression of non-measurable disease and/or appearance of new lesion/site or 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.
- Change in patient-reported pain [ Time Frame: baseline and 24 weeks ] [ Designated as safety issue: No ]"worst pain" score from the Brief Pain Inventory Short Form
|Study Start Date:||March 2007|
|Estimated Study Completion Date:||September 2013|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive oral dasatinib once daily.
Experimental: Arm II
Patients receive oral dasatinib twice daily.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00410813
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|Study Chair:||Anne F. Schott, MD||University of Michigan Cancer Center|
|Study Chair:||Catherine Van Poznak, MD||University of Michigan Cancer Center|