Metastatic Breast Cancer
Conditions
Brief summary
To evaluate the Growth Modulation Index (GMI) of the combination of metronomic capecitabine with oral digoxin in metastatic breast cancer
Detailed description
In this phase II study, the Investigators will combine metronomic capecitabine with digoxin to treat metastatic breast cancer patients who have progressed on both anthracyclines and taxanes. We hypothesize that the combination of digoxin with metronomic capecitabine may lead to increased efficacy and duration of treatment without progression with decreased side effects than standard regimen.
Interventions
DRUGCapecitabine
650 mg/m\^2 PO b.i.d.
DRUGDigoxin
0.25 mg once daily
Sponsors
Western Regional Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients ≥ 18 years of age with histologically confirmed, metastatic breast cancer resistant to anthracyclines and taxanes 2. Anthracycline resistance is defined as tumor progression during treatment or within 3 months of last dose in the metastatic setting, or recurrence within 6 months in the neoadjuvant or adjuvant setting. Alternatively, a minimum cumulative dose of anthracycline of 240 mg/m\^2 (doxorubicin) or 360 mg/m\^2 (epirubicin) has been reached, or there is contraindication to use anthracycline, the patient is also eligible 3. Taxane resistance is defined as recurrence within 4 months of the last dose in the metastatic setting or within 12 months in the adjuvant setting 4. Having progressed on anti-HER2 or hormonal therapy if they have HER2 positive or hormone-receptor positive breast cancer 5. Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2 and a life expectancy \>3 months. 6. Participants must have at least one target lesion as defined by RECIST 1.1 that allows for evaluation of tumor response 7. Absolute neutrophil count ≥ 1500 mm3, platelet count ≥ 100×109 L, hemoglobin ≥ 8.5 g/dL 8. Serum creatinine ≤1.5 times the upper limit of the normal range, total bilirubin ≤ 2 mg/dL, AST/ALT ≤ 5 times the upper limit of normal range 9. No remaining grade 2 or higher toxicity from prior cancer therapies unless judged to be clinically insignificant by the Principal Investigator 10. At least three (3) weeks from prior chemotherapy 11. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must be willing to use an acceptable contraceptive method (abstinence, oral contraceptive or double barrier method) for the duration of the study and for 30 days following the last dose of study drug, and must have a negative urine or serum pregnancy test within 2 weeks prior to beginning treatment on this trial.
Exclusion criteria
1. Inadequate renal function with a calculated creatinine clearance less than 51 mL/min. 2. History of ventricular fibrillation, sinus node or AV nodal disease, Wolff Parkinson White Syndrome, hemodynamically significant or life threatening cardiac arrhythmia. 3. Uncontrolled cardiac disease, congestive heart failure, angina or hypertension. 4. Myocardial infarction or unstable angina within 2 months of treatment. 5. Known human immunodeficiency virus (HIV) infection or chronic active Hepatitis B or C (patients are NOT required to be tested for the presence of such viruses prior to therapy on this protocol). 6. Active clinically serious infection \> CTCAE (version 4.03) Grade 2. 7. Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months. 8. Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug. 9. Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug. 10. Serious non-healing wound, ulcer, or bone fracture. 11. Major surgery or significant traumatic injury within 2 weeks of first study drug. 12. Inability to complete informed consent process and adhere to the protocol treatment plan and follow-up requirements. 13. Concurrent severe illness such as active infection, or psychiatric illness/social situations that would limit safety and compliance with study requirements. 14. Currently on anti-coagulation therapy with Coumadin, and cannot be switched other forms of anti-coagulation. 15. Patients have symptomatic untreated brain metastasis or leptomeningeal metastases or treated but still symptomatic requiring the use of steroid within the past two weeks. 16. Patients receiving any other investigational agents. Pregnant or Lactating females.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Metronomic Capecitabine With Oral Digoxin | One year | Evaluate the Growth Modulation Index (GMI) of the combination of metronomic capecitabine with oral digoxin in metastatic breast cancer |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Combination Overall Clinical Benefit by RECIST 1.1 | One year | Assess the activity of this combination in terms of overall clinical benefit rates (CBR), including complete response (CR), partial response (PR) or stable disease (SD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Capecitabine With Digoxin Capecitabine PO daily b.i.d., no breaks, starts at day 1 of the first cycle; Digoxin: once daily, starts at day -7 of the first cycle
(1 cycle - 4 weeks)
Capecitabine: 650 mg/m\^2 PO b.i.d.
Digoxin: 0.25 mg once daily | 0 |
| Total | 0 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | The study was terminated and the PI has | 16 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Metronomic Capecitabine With Oral Digoxin
Evaluate the Growth Modulation Index (GMI) of the combination of metronomic capecitabine with oral digoxin in metastatic breast cancer
Time frame: One year
Population: data were not collected
Secondary
Combination Overall Clinical Benefit by RECIST 1.1
Assess the activity of this combination in terms of overall clinical benefit rates (CBR), including complete response (CR), partial response (PR) or stable disease (SD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time frame: One year
Population: data were not collected