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DIG-HIF1 Pharmacodynamic Trial in Newly Diagnosed Operable Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01763931
First received: January 7, 2013
Last updated: October 1, 2014
Last verified: October 2014
  Purpose

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


Condition Intervention Phase
Breast Cancer
Drug: Digoxin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Changes in HIF-1 protein expression [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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:
  • Adverse events with digoxin [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 64
Study Start Date: January 2013
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Detailed Description:

Breast cancer cells grow in a low oxygen environment called hypoxia. Your 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 are able to block its function, 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. We want to learn if it blocks HIF-1 in human breast cancer tissue. We will do this by comparing the tumor tissue from your original diagnostic biopsy to tissue that is taken at the time of surgery. We will also be comparing tumor tissue of patients who are not randomized to take digoxin.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01763931

Contacts
Contact: JHCCCRO (Central Contact) 410-955-8866 jhcccro@jhmi.edu
Contact: Hopkins Breast Trials (Central Contact Backup) HopkinsBreastTrials@jhmi.edu

Locations
United States, Maryland
Kimmel Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231
Contact: JHCCCRO (CRO)    410-955-8866    jhcccro@jhmi.edu   
Contact: Hopkins Breast Trials (Back-up contact)       HopkinsBreastTrials@jhmi.edu   
Principal Investigator: Vered Stearns, M.D.         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: Vered Stearns, M.D. Sidney Kimmel Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01763931     History of Changes
Other Study ID Numbers: J1232, A-17427, NA_00072292
Study First Received: January 7, 2013
Last Updated: October 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
Digoxin

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

ClinicalTrials.gov processed this record on November 25, 2014