- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01763931
DIG-HIF-1 Pharmacodynamic Trial in Newly Diagnosed Operable Breast Cancer
January 22, 2020 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Digoxin as a Novel Inhibitor of Global Hypoxia Inducible Factor-1α (HIF-1α) Expression & Downstream Targets in Breast Cancer: DIG-HIF-1 Pharmacodynamic Trial
The purpose of this study is to learn what effects digoxin (DIG) may have on human breast cancer tissue.
Study Overview
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 Hypoxia-inducible factor (HIF)-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 the 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
Enrollment (Actual)
6
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Maryland
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Baltimore, Maryland, United States, 21231
- Kimmel Cancer Center at Johns Hopkins
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Digoxin
Digoxin administration for 2 weeks prior to surgery.
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Digoxin once daily for 2 weeks prior to definitive breast surgery.
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in HIF-1α Protein Expression
Time Frame: Baseline (biopsy prior to surgery) and at the end of 2 weeks digoxin treatment
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To assess whether two weeks of daily oral digoxin therapy, as compared to no study drug, reduces the expression of Hypoxia-inducible factor (HIF)-1α protein, measured by immunohistochemistry (IHC), in surgically resected breast cancer tissue obtained from women undergoing lumpectomy or mastectomy for invasive breast cancer.
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Baseline (biopsy prior to surgery) and at the end of 2 weeks digoxin treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Adverse Events With Digoxin Treatment
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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2 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Study Chair: Vered Stearns, M.D., Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2013
Primary Completion (Actual)
April 1, 2016
Study Completion (Actual)
April 1, 2016
Study Registration Dates
First Submitted
January 7, 2013
First Submitted That Met QC Criteria
January 8, 2013
First Posted (Estimate)
January 9, 2013
Study Record Updates
Last Update Posted (Actual)
January 31, 2020
Last Update Submitted That Met QC Criteria
January 22, 2020
Last Verified
January 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- J1232
- A-17427 (Other Identifier: Department of Defense (DoD))
- NA_00072292 (Other Identifier: JHMIRB)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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