Breast Neoplasms
Conditions
Keywords
Breast Cancer, Metastatic, Platelet
Brief summary
The purpose of this study is to determine the effects of Plavix and aspirin in women with metastatic breast cancer.
Interventions
DRUGPlavix
DRUGAspirin
Sponsors
Barnes-Jewish Hospital
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women with metastatic breast cancer who are completing planned course of chemotherapy with planned treatment break * On stable hormone therapy for at least 2 months are also eligible for the study * Estimated survival of at least 3 months * No platelet inhibitor therapy within 1 month of study entry * Platelets ≥ 100,000 * Coagulation screening tests within normal range (INR between 0.81 and 1.20) * Normal kidney and liver function as defined by: * Aspartate aminotransferase(AST)/serum glutamic oxaloacetic transaminase (SGOT))/alanine aminotransferase(ALT) ≤ 2 x Institutional Normal * Creatinine ≤ 2 x Institutional Normal * Able to provide signed, informed consent.
Exclusion criteria
* Patients going on to surgery * Patients with a serious bleeding disorder that make them inappropriate candidates for NSAID therapy * Patients with history of significant bleeding related to peptic ulcer disease * Patients on standing doses of NSAIDS or platelet function inhibitors * Patients on standing doses of anti-coagulants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Platelet Inhibition of Circulating Tumor Cells (CTCs) Measured by the Number of Patients With Detectable CTCs | Week 4 | Measured by number of patients who have detectable circulating tumor cells |
| Safety and Tolerability of Aspirin and Plavix Measured by the Number of Patients Who Discontinue the Study Drug | Maximum of 6 months | Measured by number of patients who discontinue administration of study drug because of toxicity and the incidence categorized by type. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | Baseline, 2 weeks and 1 month | Percent of patients with a given number/range of CTCs ( 0, 1-5 \>+ 5) vs. time baseline 2-weeks and 1 month for plavix & Aspirin arm and observation only |
| Mean Aspirin-Mediated Platelet Inhibition vs. Time Plotted for Plavix and Aspirin and Observation Groups | Baseline, 2 weeks and 1 month | Mean platelet inhibition vs. time plotted for Plavix & Aspirin Arm and Observation group. Citrated whole blood is added to a test carriage containing fibrinogen-coated beads and a platelet activator (arachidonic acid to synthesize thromboxane A2). Using a turbidimetric-based optical detection system, aggregation of activated platelets to fibrinogen-coated beads increase light transmittance which is reported in Aspirin Reaction Units (ARU). |
| Clopidogrel-Mediated Percent of Platelet Inhibition vs. Time Plotted for Aspirin and Plavix and Observation Groups | Baseline, 2 weeks and 1 month | Mean Clopidogrel-Mediated platelet inhibition (% inhibition) vs. time for Aspirin and Plavix and Observation groups |
| Progression Free Survival | Maximum of 6 months | — |
Countries
United States
Participant flow
Recruitment details
This study opened for enrollment in January 6, 2006 and closed enrollment in May 25, 2010
Participants by arm
| Arm | Count |
|---|---|
| Plavix and Aspirin Patients will receive a 300 mg loading dose of Plavix on day 1, followed by 75 mg/day, and aspirin 81 mg per day starting day 1. Treatment will be continued until the treating physician elects to resume systemic therapy for the treatment of breast cancer or until unacceptable toxicity is observed. A pill diary will be collected monthly to monitor patients' compliance with the medication regimen. | 24 |
| Observation Only Observation by treating physician | 24 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Disease Progression | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Total | Observation Only | Plavix and Aspirin |
|---|---|---|---|
| Age, Continuous | 55.79 years STANDARD_DEVIATION 12.97 | 58.4 years STANDARD_DEVIATION 12.06 | 50.7 years STANDARD_DEVIATION 12.01 |
| Estrogen Receptor Positivity (ER+) | 28 participants | 13 participants | 15 participants |
| Human Epidermal Growth Factor Receptor 2 Positivity (HER2+) | 18 participants | 10 participants | 8 participants |
| Number of Metastatic Sites 1 | 17 participants | 9 participants | 8 participants |
| Number of Metastatic Sites 2 | 14 participants | 7 participants | 7 participants |
| Number of Metastatic Sites ≥3 | 17 participants | 8 participants | 9 participants |
| Number of Participants Concurrently using Bisphosphonate | 21 participants | 9 participants | 12 participants |
| Number of Participants Concurrently using Trastuzumab | 14 participants | 9 participants | 5 participants |
| Number of Participants who Smoke | 9 participants | 5 participants | 4 participants |
| Number of Previous Metastatic Chemotherapy Regimens 0 | 10 participants | 4 participants | 6 participants |
| Number of Previous Metastatic Chemotherapy Regimens 1 | 13 participants | 8 participants | 5 participants |
| Number of Previous Metastatic Chemotherapy Regimens 2 | 10 participants | 6 participants | 4 participants |
| Number of Previous Metastatic Chemotherapy Regimens ≥3 | 15 participants | 6 participants | 9 participants |
| Number of Previous Metastatic Endocrine Therapies 0 | 19 participants | 11 participants | 8 participants |
| Number of Previous Metastatic Endocrine Therapies 1 | 10 participants | 3 participants | 7 participants |
| Number of Previous Metastatic Endocrine Therapies ≥2 | 19 participants | 10 participants | 9 participants |
| Region of Enrollment United States | 48 participants | 24 participants | 24 participants |
| Sex: Female, Male Female | 48 Participants | 24 Participants | 24 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| The Number of Participants with Detectable Positive Circulating Tumor Cells (CTCs=>1) at Baseline | 30 participants | 18 participants | 12 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 24 | 24 / 24 |
| serious Total, serious adverse events | 3 / 24 | 1 / 24 |
Outcome results
Primary
Platelet Inhibition of Circulating Tumor Cells (CTCs) Measured by the Number of Patients With Detectable CTCs
Measured by number of patients who have detectable circulating tumor cells
Time frame: Week 4
Population: Plavix \& Aspirin arm has 19 evaluable patients. 5 withdrew before 1-month data collection: death n=1 and withdrawal of consent n=1 prior to starting; surgery plans n=1; patient preference n=1; platelet inhibition use n=1; Observation only arm had 23 evaluable patients ; 1 patient withdrew during the first month due to disease progression.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Plavix and Aspirin | Platelet Inhibition of Circulating Tumor Cells (CTCs) Measured by the Number of Patients With Detectable CTCs | 11 participants |
| Observation Only | Platelet Inhibition of Circulating Tumor Cells (CTCs) Measured by the Number of Patients With Detectable CTCs | 15 participants |
Primary
Safety and Tolerability of Aspirin and Plavix Measured by the Number of Patients Who Discontinue the Study Drug
Measured by number of patients who discontinue administration of study drug because of toxicity and the incidence categorized by type.
Time frame: Maximum of 6 months
Population: Plavix and Aspirin: 1 patient withdrew consent prior to starting 1 patient died prior to starting
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Plavix and Aspirin | Safety and Tolerability of Aspirin and Plavix Measured by the Number of Patients Who Discontinue the Study Drug | Bleeding (possibly related) | 1 participants |
| Plavix and Aspirin | Safety and Tolerability of Aspirin and Plavix Measured by the Number of Patients Who Discontinue the Study Drug | Back pain (unlikely related) | 1 participants |
| Observation Only | Safety and Tolerability of Aspirin and Plavix Measured by the Number of Patients Who Discontinue the Study Drug | Bleeding (possibly related) | 0 participants |
| Observation Only | Safety and Tolerability of Aspirin and Plavix Measured by the Number of Patients Who Discontinue the Study Drug | Back pain (unlikely related) | 0 participants |
Secondary
Clopidogrel-Mediated Percent of Platelet Inhibition vs. Time Plotted for Aspirin and Plavix and Observation Groups
Mean Clopidogrel-Mediated platelet inhibition (% inhibition) vs. time for Aspirin and Plavix and Observation groups
Time frame: Baseline, 2 weeks and 1 month
Population: Mean Platelet inhibition Denominator for Plavix \& Aspirin arm baseline n=22, 2 weeks n=20, 1 month n=19 Denominator for control group baseline n=24 , 2-weeks n=19, 1 month n=23
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Plavix and Aspirin | Clopidogrel-Mediated Percent of Platelet Inhibition vs. Time Plotted for Aspirin and Plavix and Observation Groups | Baseline | 9.85 percentage of platelet inhibition | Standard Deviation 16.13 |
| Plavix and Aspirin | Clopidogrel-Mediated Percent of Platelet Inhibition vs. Time Plotted for Aspirin and Plavix and Observation Groups | 2 weeks | 37.35 percentage of platelet inhibition | Standard Deviation 30.38 |
| Plavix and Aspirin | Clopidogrel-Mediated Percent of Platelet Inhibition vs. Time Plotted for Aspirin and Plavix and Observation Groups | 1 month | 35.56 percentage of platelet inhibition | Standard Deviation 30.9 |
| Observation Only | Clopidogrel-Mediated Percent of Platelet Inhibition vs. Time Plotted for Aspirin and Plavix and Observation Groups | Baseline | 13.00 percentage of platelet inhibition | Standard Deviation 21.93 |
| Observation Only | Clopidogrel-Mediated Percent of Platelet Inhibition vs. Time Plotted for Aspirin and Plavix and Observation Groups | 2 weeks | 9.05 percentage of platelet inhibition | Standard Deviation 7.96 |
| Observation Only | Clopidogrel-Mediated Percent of Platelet Inhibition vs. Time Plotted for Aspirin and Plavix and Observation Groups | 1 month | 7.05 percentage of platelet inhibition | Standard Deviation 7.07 |
Secondary
Mean Aspirin-Mediated Platelet Inhibition vs. Time Plotted for Plavix and Aspirin and Observation Groups
Mean platelet inhibition vs. time plotted for Plavix & Aspirin Arm and Observation group. Citrated whole blood is added to a test carriage containing fibrinogen-coated beads and a platelet activator (arachidonic acid to synthesize thromboxane A2). Using a turbidimetric-based optical detection system, aggregation of activated platelets to fibrinogen-coated beads increase light transmittance which is reported in Aspirin Reaction Units (ARU).
Time frame: Baseline, 2 weeks and 1 month
Population: Denominator for Plavix \& Aspirin arm baseline n=22, 2 weeks n=20, 1 month n=19 Denominator for Observation only arm baseline n=24 , 2-weeks n=19, 1 month n=23
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Plavix and Aspirin | Mean Aspirin-Mediated Platelet Inhibition vs. Time Plotted for Plavix and Aspirin and Observation Groups | Baseline Aspirin Reaction UnitsARU | 610.39 Aspirin Reaction Units | Standard Deviation 57.64 |
| Plavix and Aspirin | Mean Aspirin-Mediated Platelet Inhibition vs. Time Plotted for Plavix and Aspirin and Observation Groups | 2 weeks ARU | 435.33 Aspirin Reaction Units | Standard Deviation 56.5 |
| Plavix and Aspirin | Mean Aspirin-Mediated Platelet Inhibition vs. Time Plotted for Plavix and Aspirin and Observation Groups | 1 month ARU | 455.44 Aspirin Reaction Units | Standard Deviation 94.7 |
| Observation Only | Mean Aspirin-Mediated Platelet Inhibition vs. Time Plotted for Plavix and Aspirin and Observation Groups | Baseline Aspirin Reaction UnitsARU | 579.81 Aspirin Reaction Units | Standard Deviation 92.1 |
| Observation Only | Mean Aspirin-Mediated Platelet Inhibition vs. Time Plotted for Plavix and Aspirin and Observation Groups | 2 weeks ARU | 578.35 Aspirin Reaction Units | Standard Deviation 151.1 |
| Observation Only | Mean Aspirin-Mediated Platelet Inhibition vs. Time Plotted for Plavix and Aspirin and Observation Groups | 1 month ARU | 593.58 Aspirin Reaction Units | Standard Deviation 88.81 |
Secondary
Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time
Percent of patients with a given number/range of CTCs ( 0, 1-5 \>+ 5) vs. time baseline 2-weeks and 1 month for plavix & Aspirin arm and observation only
Time frame: Baseline, 2 weeks and 1 month
Population: Denominator for Plavix \& Aspirin arm at Baseline=22, at 2 weeks =20, at 4 weeks =19 Denominator for Observation only at Baseline=24, at 2 weeks=19, at 4 weeks =23
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Plavix and Aspirin | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | 1 month 0 CTCs | 41.18 percentage of participants |
| Plavix and Aspirin | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | 1 month 1-5 CTCs | 52.94 percentage of participants |
| Plavix and Aspirin | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | 2 week 0 CTCs | 45.00 percentage of participants |
| Plavix and Aspirin | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | Baseline >=5 CTS | 15.00 percentage of participants |
| Plavix and Aspirin | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | Baseline 1-5 CTCs | 45.00 percentage of participants |
| Plavix and Aspirin | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | 2 weeks >=5 CTCs | 21.05 percentage of participants |
| Plavix and Aspirin | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | Baseline 0 CTCs | 40.00 percentage of participants |
| Plavix and Aspirin | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | 1 month >=5 CTCs | 5.88 percentage of participants |
| Plavix and Aspirin | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | 2 weeks 1-5 CTCs | 31.58 percentage of participants |
| Observation Only | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | 1 month >=5 CTCs | 10.00 percentage of participants |
| Observation Only | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | 2 week 0 CTCs | 40.00 percentage of participants |
| Observation Only | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | 1 month 0 CTCs | 35.00 percentage of participants |
| Observation Only | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | Baseline 1-5 CTCs | 63.64 percentage of participants |
| Observation Only | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | 2 weeks 1-5 CTCs | 45.00 percentage of participants |
| Observation Only | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | 1 month 1-5 CTCs | 55.00 percentage of participants |
| Observation Only | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | Baseline >=5 CTS | 13.64 percentage of participants |
| Observation Only | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | 2 weeks >=5 CTCs | 15.00 percentage of participants |
| Observation Only | Percentage of Patients With a Given Absolute Number of Circulating Tumor Cells (Broken Into Categories) Plotted Against Time | Baseline 0 CTCs | 22.73 percentage of participants |
Secondary
Progression Free Survival
Time frame: Maximum of 6 months
Population: This trial was terminated early due to futility, subjects were not followed for progression free-survival.