Breast CancerPhase 2NCT01763931
DIG-HIF-1 Pharmacodynamic Trial in Newly Diagnosed Operable Breast Cancer
A Phase 2 study testing Digoxin in people with Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
The purpose of this study is to learn what effects digoxin (DIG) may have on human breast cancer tissue. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Digoxin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2013to 1 Apr 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Kimmel Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
About this study
Official title: 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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Digoxin
- Keywords
- Digoxin
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DigoxinDrug
Digoxin once daily for 2 weeks prior to definitive breast surgery.
| Study group | Role | What they receive |
|---|---|---|
| Digoxin | Experimental | Digoxin administration for 2 weeks prior to surgery. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2013 (estimated)
- Study startJan 2013
- Primary completion1 Apr 2016
- Study completion1 Apr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Vered Stearns, M.D., Study chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01763931
- Sponsor's protocol ID
- J1232
- Other IDs
- A-17427, NA_00072292
- Status last verified
- Jan 2020
- First submitted
- 7 Jan 2013
- Last updated
- 31 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Digoxin as a Novel Inhibitor of Global Hypoxia Inducible Factor-1α (HIF-1α) Expression & Downstream Targets in Breast Cancer: DIG-HIF-1 Pharmacodynamic Trial
- ClinicalTrials.gov ID
- NCT01763931
- Acronym / sponsor ID
- J1232
- Conditions
- Breast Cancer
- Keywords
- Digoxin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- Jan 2013
- Primary completion
- 1 Apr 2016 (actual)
- Study completion
- 1 Apr 2016 (actual)
- First posted
- 9 Jan 2013 (estimated)
- Results
- Posted 31 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to learn what effects digoxin (DIG) may have on human breast cancer tissue.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Digoxin | Experimental | Drug: DigoxinDigoxin administration for 2 weeks prior to surgery. |
| 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DigoxinDigoxin once daily for 2 weeks prior to definitive breast surgery. | Drug | Digoxin |
Primary outcome
Change in HIF-1α Protein Expression
Time frame: Baseline (biopsy prior to surgery) and at the end of 2 weeks digoxin treatment
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.
1 secondary outcome
Number of Participants With Adverse Events With Digoxin Treatment
Time frame: 2 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vered Stearns, M.D. study chair
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Digoxin in people with Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in HIF-1α Protein Expression (time frame: Baseline (biopsy prior to surgery) and at the end of 2 weeks digoxin treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2020.