DIG-HIF-1 Pharmacodynamic Trial in Newly Diagnosed Operable Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Digoxin
Intervention description: Digoxin once daily for 2 weeks prior to definitive breast surgery.
Intervention MeSH terms: Digoxin
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: Female
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Digoxin

Summary:

      The purpose of this study is to learn what effects digoxin (DIG) may have on human breast
      cancer tissue.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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 estrogen
             receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor 2
             (HER2) status

          -  Patients must not have received any prior treatment of any kind to treat the current
             breast cancer.

          -  Prior use of hormone contraceptives and replacement therapy is allowed, but must have
             been discontinued at least 30 days prior to the diagnostic biopsy.

          -  Eastern Cooperative Oncology Group (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

        Exclusion Criteria:

          -  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 forced expiratory volume (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
             study requirements

          -  Any medical condition which in the opinion of the investigator puts the patient at
             risk of potentially serious complications while on this therapy