DIG-HIF-1 Pharmacodynamic Trial in Newly Diagnosed Operable Breast Cancer

NCT01763931 | Completed Phase 2 Results

• 3 other identifiers: J1232A-17427NA_00072292
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Breast Cancer

Keywords

Digoxin

Outcome Measures

Primary Outcomes (1)

• Change in HIF-1α Protein Expression

  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.

  Baseline (biopsy prior to surgery) and at the end of 2 weeks digoxin treatment

Secondary Outcomes (1)

• Number of Participants With Adverse Events With Digoxin Treatment

  2 weeks

Study Arms (2)

Digoxin

EXPERIMENTAL

Digoxin administration for 2 weeks prior to surgery.

Drug: Digoxin

No drug administration prior to surgery

NO INTERVENTION

Group of participants who will not receive digoxin; however, tissue will be collected at time of definitive breast surgery.

Interventions

Digoxin DRUG

Digoxin once daily for 2 weeks prior to definitive breast surgery.

Digoxin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female sex
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• United States Department of Defense: collaborator

Study Sites (1)

Kimmel Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Digoxin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Limitations and Caveats

The pre-operative setting was challenging for accrual and we did not meet our accrual goals. Therefore, the study was closed to accrual early. Only 6 out of 64 planned participants were enrolled, therefore there was not enough data to analyze.

Results Point of Contact

• Title: Vered Stearns, MD
• Organization: SKCCC at Johns Hopkins

HopkinsBreastTrials@jhmi.edu

410-614-1361

Study Officials

• Vered Stearns, M.D.

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2013
• First Posted: January 9, 2013
• Study Start: January 1, 2013
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: January 31, 2020
• Results First Posted: January 31, 2020

Record last verified: 2020-01

Locations

US (1)