DIG-HIF1 Pharmacodynamic Trial in Newly Diagnosed Operable Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01763931
Recruitment Status : Active, not recruiting
First Posted : January 9, 2013
Last Update Posted : April 24, 2018
United States Department of Defense
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
The purpose of this study is to learn what effects digoxin may have on human breast cancer tissue.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Digoxin Phase 2

Detailed Description:
Breast cancer cells grow in a low oxygen environment called hypoxia. The body normally controls the amount of oxygen in cells with what is known as HIF-1, hypoxia inducible factor 1. HIF-1 helps cancer cells grow in low oxygen environments; therefore, if this function can be blocked, it may make it harder for breast cancer cells to grow. Digoxin is a drug that has been shown to block HIF-1 in lab studies. The investigators want to learn if it blocks HIF-1 in human breast cancer tissue. This will be done by comparing the tumor tissue from your original diagnostic biopsy to tissue that is taken at the time of surgery. The investigators will also be comparing tumor tissue of patients who are not randomized to take digoxin.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Digoxin as a Novel Inhibitor of Global Hypoxia Inducible Factor-1α (HIF-1α) Expression & Downstream Targets in Breast Cancer: DIG-HIF1 Pharmacodynamic Trial
Study Start Date : January 2013
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Digoxin
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Digoxin
Digoxin administration for 2 weeks prior to surgery.
Drug: Digoxin
Digoxin once daily for 2 weeks prior to definitive breast surgery.
No Intervention: No drug administration prior to surgery
Group of participants who will not receive digoxin; however, tissue will be collected at time of definitive breast surgery.

Primary Outcome Measures :
  1. Changes in HIF-1 protein expression [ Time Frame: 2 weeks ]
    To evaluate whether two weeks of daily oral digoxin therapy, as compared to no study drug, reduces the expression of HIF-1α protein, measured by immunohistochemistry (IHC), in surgically resected breast cancer tissue obtained from women undergoing lumpectomy or mastectomy for invasive breast cancer.

Secondary Outcome Measures :
  1. Adverse events with digoxin [ Time Frame: 2 weeks ]
    To assess safety and tolerability of two weeks of digoxin therapy in the pre-surgical setting graded according to Common Terminology Criteria for Adverse Events (CTCAE), version 4.

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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 ER, PR or 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.
  • 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01763931

United States, Maryland
Kimmel Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
United States Department of Defense
Study Chair: Vered Stearns, M.D. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Identifier: NCT01763931     History of Changes
Other Study ID Numbers: J1232
A-17427 ( Other Identifier: Department of Defense (DoD) )
NA_00072292 ( Other Identifier: JHMIRB )
First Posted: January 9, 2013    Key Record Dates
Last Update Posted: April 24, 2018
Last Verified: April 2018

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Anti-Arrhythmia Agents
Cardiotonic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs