A Phase 2 interventional study of dasatinib in Breast Cancer and Metastatic Cancer, sponsored by SWOG Cancer Research Network. Completed at 117 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-07-02.
Sponsored by SWOG Cancer Research Network · Phase 2, Interventional, and Treatment
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:
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.
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.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 85 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →SWOG Cancer Research Network is the lead sponsor of 328 studies on the registry; 37 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 17 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
DISEASE CHARACTERISTICS:
Diagnosis of breast carcinoma meeting the following criteria:
Bone metastasis-predominant disease, defined as the presence of ≥ 1 bone metastasis with or without nonbone (visceral or soft tissue) disease where the number of bone metastases is at least the number of measurable visceral target lesions
Must meet 1 of the following criteria:
Nonmeasurable disease with rising serum CA 15-3, CA 27-29, CEA, or CA-125 documented by 2 consecutive measurements taken ≥ 14 days apart with the most recent measurement being within the past 42 days
No symptomatic brain or CNS metastases
Hormone receptor status known
PATIENT CHARACTERISTICS:
No uncontrolled concurrent condition that would preclude the ability to take oral medication, including the following:
No clinically significant cardiac disease, including the following:
No concurrent active malignancy
PRIOR CONCURRENT THERAPY:
At least 7 days since prior and no concurrent antiplatelet agents, including any of the following*:
At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:
At least 7 days since prior and no concurrent medications that prolong the QTc interval, including any of the following:
No other concurrent antineoplastic therapy for breast cancer, including any of the following:
Patients receive oral dasatinib once daily.
Drug: dasatinib
Patients receive oral dasatinib twice daily.
Drug: dasatinib
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.
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
| Milestone | Dasatinib, 100 mg, Daily | Dasatinib, 70 mg, Twice Daily |
|---|---|---|
| Started | 43 | 42 |
| Eligible | 41 | 38 |
| Completed | 0 | 0 |
| Not completed | 43 | 42 |
| Withdrew: Adverse event | 6 | 11 |
| Withdrew: Progression | 32 | 21 |
| Withdrew: Not protocol specified | 3 | 4 |
| Withdrew: Ineligible | 2 | 4 |
| Withdrew: Death | 0 | 2 |
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.
| weeks | Dasatinib, 100 mg, Daily | Dasatinib, 70 mg, Twice Daily |
|---|---|---|
| Progression-free Survival | 10.3 (8.4 to 16.7) | 15.3 (8.7 to 20.1) |
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.
| participants | Dasatinib, 100 mg, Daily | Dasatinib, 70 mg, Twice Daily |
|---|---|---|
| Partial Response | 1 | 0 |
| Stable/No Response | 14 | 18 |
| Increasing Disease | 20 | 10 |
| Assessment Inadequate | 6 | 10 |
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.
No measurements were reported for this outcome.
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.
| participants | Dasatinib |
|---|---|
| Circulating Tumor Cells (CTC) Response Rate | 4 |
Analysis included mean values of the serum biomarker NTx at baseline, 4, and 8 weeks.
| nM BCE | NTx at Baseline | NTx at 4 Weeks | NTx at 8 Weeks |
|---|---|---|---|
| Change in Serum Bone Turnover Markers Over Time -- NTx | 21.84 ± 12.32 | 19.23 ± 11.32 | 12.88 ± 13.09 |
Analysis included mean values of the serum biomarker BAP at baseline, 4, and 8 weeks.
| ug/L | BAP at Baseline | BAP at 4 Weeks | BAP at 8 Weeks |
|---|---|---|---|
| Change in Serum Bone Turnover Markers Over Time -- BAP | 24.07 ± 15.95 | 24.35 ± 13.94 | 25.61 ± 14.05 |
Analysis included mean values of the serum biomarkers sRANKL, IL-6, DKK, VEGF at baseline, 4, and 8 weeks.
| pg/mL | Serum Biomarker at Baseline | Serum Biomarker at 4 Weeks | Serum Biomarker at 8 Weeks |
|---|---|---|---|
| DKK | 1157.64 ± 1465.83 | 1470.50 ± 1985.09 | 1575.05 ± 1993.44 |
| IL-6 | 250.17 ± 1588.17 | 19.03 ± 73.70 | 32.03 ± 190.36 |
| VEGF | 459.01 ± 324.89 | 424.21 ± 355.33 | 412.33 ± 346.58 |
| sRANKL | 772172 ± 1580514 | 531173 ± 910765 | 553459 ± 864151 |
Analysis included mean values of the serum biomarker OC at baseline, 4, and 8 weeks.
| ng/mL | OC at Baseline | OC at 4 Weeks | OC at 8 Weeks |
|---|---|---|---|
| Change in Serum Bone Turnover Markers Over Time -- OC | 11.08 ± 7.76 | 13.10 ± 9.17 | 13.54 ± 10.20 |
Analysis included mean values of the serum biomarker OPG at baseline, 4, and 8 weeks.
| pmol/L | OPG at Baseline | OPG at 4 Weeks | OPG at 8 Weeks |
|---|---|---|---|
| Change in Serum Bone Turnover Markers Over Time -- OPG | 4.56 ± 5.44 | 6.53 ± 9.46 | 6.71 ± 10.09 |
Analysis included mean values of the serum biomarker TRAP at baseline, 4, and 8 weeks.
| U/L | TRAP at Baseline | TRAP at 4 Weeks | TRAP at 8 Weeks |
|---|---|---|---|
| Change in Serum Bone Turnover Markers Over Time -- TRAP | 6.83 ± 6.42 | 5.41 ± 4.23 | 5.59 ± 4.40 |
Only adverse events that are possibly, probably or definitely related to study drug are reported.
| Participants | Dasatinib, 100 mg, Daily | Dasatinib, 70 mg, Twice Daily |
|---|---|---|
| ALT, SGPT (serum glutamic pyruvic transaminase) | 1 | 2 |
| AST, SGOT | 1 | 1 |
| Albumin, serum-low (hypoalbuminemia) | 0 | 1 |
| Anorexia | 0 | 1 |
| Dehydration | 0 | 1 |
| Diarrhea | 0 | 2 |
| Dyspnea (shortness of breath) | 1 | 4 |
| Fatigue (asthenia, lethargy, malaise) | 0 | 6 |
| Hemoglobin | 0 | 1 |
| Inf w/normal ANC or Gr 1-2 neutrophils - Skin | 0 | 1 |
| Inf w/normal ANC or Gr 1-2 neutrophils - UTI | 1 | 1 |
| Infection with unknown ANC - Dental-tooth | 1 | 0 |
| Left ventricular systolic dysfunction | 2 | 1 |
| Lymphopenia | 0 | 1 |
| Nausea | 0 | 1 |
| Neutrophils/granulocytes (ANC/AGC) | 0 | 1 |
| Pain - Bone | 1 | 1 |
| Pain - Buttock | 1 | 0 |
| Pain - Chest wall | 1 | 0 |
| Pain - Chest/thorax NOS | 1 | 0 |
| Pain - Head/headache | 1 | 1 |
| Platelets | 2 | 1 |
| Pleural effusion (non-malignant) | 1 | 2 |
| Pneumonitis/pulmonary infiltrates | 1 | 0 |
| Potassium, serum-low (hypokalemia) | 1 | 3 |
| Pulmonary hypertension | 0 | 1 |
| Pulmonary/Upper Respiratory-Other (Specify) | 0 | 1 |
| Rash/desquamation | 0 | 1 |
| Sodium, serum-low (hyponatremia) | 0 | 1 |
| Vomiting | 0 | 1 |
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.
| units on a scale | Dasatinib - Baseline | Dasatinib - Week 8 | Dasatinib - Week 16 | Dasatinib - Week 24 |
|---|---|---|---|---|
| Mean Patient-reported Pain | 3.37 ± 2.93 | 3.82 ± 3.04 | 3.06 ± 2.61 | 3.73 ± 3.03 |
Collected over Up to 2 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dasatinib, 100 mg, Daily | — | 6/41 (14.6%) | 34/41 (82.9%) |
| Dasatinib, 70 mg, Twice Daily | — | 12/38 (31.6%) | 36/38 (94.7%) |
| Event | Dasatinib, 100 mg, Daily | Dasatinib, 70 mg, Twice Daily |
|---|---|---|
| Pleural effusion (non-malignant)Respiratory, thoracic and mediastinal disorders | 1/41 | 2/38 |
| Pneumonitis/pulmonary infiltratesRespiratory, thoracic and mediastinal disorders | 2/41 | 0/38 |
| Left ventricular systolic dysfunctionCardiac disorders | 0/41 | 1/38 |
| ConstipationGastrointestinal disorders | 0/41 | 1/38 |
| Death not associated with CTCAE term - Death NOSGeneral disorders | 0/41 | 1/38 |
| Sudden deathGeneral disorders | 0/41 | 1/38 |
| Inf w/normal ANC or Gr 1-2 neutrophils - SkinInfections and infestations | 0/41 | 1/38 |
| Inf w/normal ANC or Gr 1-2 neutrophils - UTIInfections and infestations | 1/41 | 1/38 |
| Rash: dermatitis associated w/ChemoradiationInjury, poisoning and procedural complications | 0/41 | 1/38 |
| AnorexiaMetabolism and nutrition disorders | 0/41 | 1/38 |
| Event | Dasatinib, 100 mg, Daily | Dasatinib, 70 mg, Twice Daily |
|---|---|---|
| HemoglobinBlood and lymphatic system disorders | 16/41 | 22/38 |
| NauseaGastrointestinal disorders | 15/41 | 19/38 |
| Fatigue (asthenia, lethargy, malaise)General disorders | 19/41 | 19/38 |
| AST, SGOTInvestigations | 10/41 | 16/38 |
| DiarrheaGastrointestinal disorders | 10/41 | 14/38 |
| ALT, SGPT (serum glutamic pyruvic transaminase)Investigations | 7/41 | 12/38 |
| Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders | 7/41 | 12/38 |
| Pain - BackMusculoskeletal and connective tissue disorders | 12/41 | 4/38 |
| Glucose, serum-high (hyperglycemia)Metabolism and nutrition disorders | 11/41 | 9/38 |
| Pain - Head/headacheNervous system disorders | 11/41 | 9/38 |
All eligible participants
| Age, Continuous(years) | Dasatinib, 100 mg, Daily | Dasatinib, 70 mg, Twice Daily | Total |
|---|---|---|---|
| Median | 60 (37 to 82) | 65 (27 to 86) | 60 (27 to 86) |
| Sex: Female, Male(Participants) | Dasatinib, 100 mg, Daily | Dasatinib, 70 mg, Twice Daily | Total |
|---|---|---|---|
| Female | 41 | 38 | 79 |
| Male | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Dasatinib, 100 mg, Daily | Dasatinib, 70 mg, Twice Daily | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 2 | 2 |
| Not Hispanic or Latino | 36 | 34 | 70 |
| Unknown or Not Reported | 5 | 2 | 7 |
| Race/Ethnicity, Customized(participants) | Dasatinib, 100 mg, Daily | Dasatinib, 70 mg, Twice Daily | Total |
|---|---|---|---|
| White | 38 | 35 | 73 |
| Black | 1 | 2 | 3 |
| Pacific Islander | 1 | 0 | 1 |
| Native American | 1 | 0 | 1 |
| Asian | 0 | 1 | 1 |
| Use of trastuzumab at time of registration(participants) | Dasatinib, 100 mg, Daily | Dasatinib, 70 mg, Twice Daily | Total |
|---|---|---|---|
| Yes | 1 | 0 | 1 |
| No | 40 | 38 | 78 |
Showing the first 100 of 117 sites.
This study is completed, as verified in May 2017. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
SWOG Cancer Research Network