Digoxin as a Novel Inhibitor of Global Hypoxia Inducible Factor-1α (HIF-1α) Expression & Downstream Targets in Breast Cancer: DIG-HIF1 Pharmacodynamic Trial
- Female sex
- 18-70 years of age at time of consent.
- Histologically confirmed infiltrating carcinoma of the breast (Stage I-III)
- Unresected disease that meets scheduled to undergo definitive surgery; tumor size ≥
1cm; grade 2 or 3 tumor or Ki-67 proliferation index of ≥ 10%; and, any ER, PR or
- Patients must not have received any prior treatment of any kind to treat the current
- Prior use of hormone contraceptives and replacement therapy is allowed, but must have
been discontinued at least 30 days prior to the diagnostic biopsy.
- ECOG performance status of 0 or 1 (Karnofsky 80%-100%)
- Patients must have normal organ and marrow function: absolute neutrophil count (ANC)
≥ 1,500/mm3; platelet count ≥ 100,000/mm3; bilirubin (total) less than or equal to
the upper limit of normal; creatinine ≤ 1.5 times the upper limit of normal with
creatinine clearance ≥ 50 mL/min using the Modified Cockcroft-Gault method; and, all
of the following within normal limits: thyroid stimulating hormone (TSH), magnesium,
potassium, sodium, calcium.
- Heart rate > 60 beats/minute and < 100 beats/minute (clinical exam).
- Not pregnant or nursing
- Ability to understand and the willingness to sign a written informed consent document
- Current use of any investigational agents
- Radiological evidence of metastatic disease
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to digoxin
- Concomitant use of these drugs at baseline and for the duration of digoxin
administration (if randomized to receive it): the calcium channel blockers diltiazem
or verapamil; cardiac arrhythmic agents (such as quinidine, amiodarone); indomethacin
(Indocin); alprazolam (Xanax); diuretics (such as furosemide, spironolactone,
itraconazole); beta-blockers (such as atenolol, metoprolol); calcium carbonate
antacids (e.g., Maalox, Tums, Rolaids); proton pump inhibitors; antidiarrheal
adsorbents (kaolin and pectin); antibiotics; other P450 inducer/inhibitors. NOTE:
Patients already receiving digoxin are also excluded.
- Presence of any of the following on electrocardiogram (ECG): atrial arrhythmias,
including atrial fibrillation and flutter; AV block; heart rate < 60 beats/minute and
> 100 beats/minute; ventricular Fibrillation; ventricular tachycardia; premature
ventricular contractions; Wolff-Parkinson-White syndrome. NOTE: Any questions on
cardiac eligibility should be reviewed by the Study Cardiologist for approval in
advance of enrollment.
- History of any of the following, unless approval is given by the Protocol Chair:
heart disease, including acute myocardial infarction; cardiac arrhythmias, including
sick sinus syndrome; pulmonary disease with a known FEV of <1.5 or on oxygen;
gastrointestinal disease, surgery or malabsorption that could potentially impact the
absorption of the study drug; patients requiring the use of a feeding tube; inability
to swallow tablets
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that will limit compliance with
- Any medical condition which in the opinion of the investigator puts the patient at
risk of potentially serious complications while on this therapy