Breast CancerEarly Phase 1NCT03928210
Digoxin Induced Dissolution of CTC Clusters
A Early Phase 1 study testing Digoxin in people with Breast Cancer and Circulating Tumor Cells (CTCs), run by University Hospital, Basel, Switzerland at 3 sites in Switzerland.
Trial summary
This single arm therapeutic exploratory study of digoxin in patients with advanced or metastatic breast cancer investigates whether cardiac glycosides are able to disrupt CTC clusters in breast cancer patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Circulating Tumor Cells (CTCs)
- What is being tested?
- Digoxin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 3 sitesSwitzerland
- Study dates
- 8 Jul 2020to 1 Dec 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed Consent as documented by signature
- Diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease not amenable to resection, radiation therapy or systemic therapy with curative intent
- Adequate organ and marrow function
Who cannot join
- Patients on treatment with digoxin or digitoxin
- Patients with atrial fibrillation or atrial flutter
- Ventricular Fibrillation or ventricular tachycardia,
- Atrioventricular heart block 2nd or 3rd degree, sick sinus syndrome or sinus bradycardia,
- Wolff-Parkinson-White Syndrome
- Hypokalemia, hypercalcemia, hypomagnesemia, hypoxia,
Show all 19Show fewer
- Hypertrophic cardiomyopathy, aortic aneurysm
- Simultaneous intravenous application of calcium salts
- Known hypersensitivity to Digoxin, other cardiac glycosides or included compounds
- Known drug interactions of ongoing cancer therapy with digoxin
- Women who are pregnant or breast feeding,
- Intention to become pregnant during the course of the study,
- Lack of safe contraception
- Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease)
- Known or suspected non-compliance, drug or alcohol abuse
- Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
- Participation in another study with investigational drug within the 30 days preceding and during the present study,
- Previous enrolment into the current study,
- Enrolment of the investigator, his/her family members, employees and other dependent persons
Trial locations and contacts
3 sites in 1 country.
Switzerland3 sites
Breast Cancer Center, University Hospital Basel
Basel, 4031
Kantonspital Baselland (KSBL)
Liestal, Basel-Landschaft, 4410
University Hospital Zurich (USZ)
Zurich, 8091
About this study
Official title: Effect of Digoxin on Clusters of Circulating Tumor Cells (CTCs) in Breast Cancer Patients
This single arm therapeutic exploratory study of digoxin in patients with advanced or metastatic breast cancer investigates whether cardiac glycosides are able to disrupt CTC clusters in breast cancer patients.
Read the detailed description
Circulating tumor cells (CTCs) are considered to be precursors of metastasis in various cancer types and are found in the blood of cancer patients as single CTCs and CTC clusters, with the latter featuring a higher ability to seed metastasis.
CTC cluster share several properties that commonly feature stem cell biology which drive metastases formation. Preclinical data shows that CTC clusters can be disaggregated into single cells by the treatment with cardiac glycosides such as digoxin. This single arm therapeutic exploratory study of digoxin in patients with advanced or metastatic breast cancer investigates whether cardiac glycosides are able to disrupt CTC clusters in breast cancer patients.
Patients with advanced or metastatic breast cancer in whom CTC clusters could be identified will receive an individualized daily maintenance dose of digoxin adapted to their kidney function. Blood samples for analyses of digoxin serum level and mean CTC cluster size will be drawn at specified time points.
- Conditions
- Breast Cancer, Circulating Tumor Cells (CTCs)
- Being tested
- Digoxin
- Keywords
- cluster of circulating tumor cells (CTCs), cardiac glycosides, digoxin
- Medical subject headings
- Breast Neoplasms, Neoplastic Cells, Circulating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DigoxinDrug
Also called Lenoxin Mite, DIGOXIN Juvisé
Patients will receive a daily maintenance dose of digoxin. The daily dose of digoxin will be calculated according to the renal function and the target serum digoxin concentration and applied in an adjusted regimen based on the availability of 0.125 mg and 0.25 mg pills in the morning (before 10 am). Blood samples for analyses of mean CTC cluster size will be drawn at screening, on day 0 (2 hrs after first oral intake), on day 3 and on day 7. Depending on the digoxin serum level maintenance therapy with digoxin will be continued up to 3 weeks if the digoxin serum level on day 7 or day 14 is below 0.70 ng/ml. For the third week of maintenance therapy individual dose adjustments will be carried out as needed.
| Study group | Role | What they receive |
|---|---|---|
| Digoxin | Experimental | Digoxin 0.125 mg or 0.25 mg administered once daily for 7 days or until symptoms of toxicity Generic e.g. DIGOXIN Juvisé or Lenoxin Mite Receives: Drug: Digoxin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mean CTC cluster size (in ng/ml)
mean CTC cluster size (in patients with a digoxin serum level above 0.7 ng/ml) after treatment will be compared to mean CTC-cluster size before treatment
Measured: Blood samples drawn at Screening, on day 0 (2 hours after first oral intake of digoxin), on day 3, on day 7, on day 10, on day 14, on day 17 and on day 21 after first oral intake of digoxin
Secondary outcomes (2)
Change in mean CTC cluster number
number of CTC-clusters before and after treatment will be compared
Measured: Blood samples drawn at Screening, on day 0 (2 hours after first oral intake of digoxin), on day 3, on day 7, on day 10, on day 14, on day 17 and on day 21 after first oral intake of digoxin
Average time to dissolution of CTC Clusters (in days)
average time to dissolution of CTC clusters
Measured: Blood samples drawn at Screening, on day 0 (2 hours after first oral intake of digoxin), on day 3, on day 7, on day 10, on day 14, on day 17 and on day 21 after first oral intake of digoxin
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2019
- Study start8 Jul 2020
- Primary completion1 Dec 2023
- Study completion1 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Patients with at least one CTC cluster (if homotypic ≥ 2 CTCs, if heterotypic ≥ 1 CTC and ≥ 1 white blood cell (WBC)) at screening entered the treatment phase. During treatment phase, patients received a daily maintenance dose of digoxin for a total of seven days, with a digoxin target level of ≥ 0.7 ng/ml in serum during treatment. Blood draws for capture and enumeration of CTCs and CTC clusters were obtained on day 0 (pre- and 2 hours post digoxin), day 3 and day 7. Regular study visits included clinical and laboratory assessments such as vital signs, electrocardiogram (ECG), serious adverse events (SAE), and digoxin serum levels on day 0 and 7.
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- ETH Zurich - The Aceto Lab
- Responsible party
- Sponsor
- Investigators
- Christian Kurzeder, PD Dr. med, Principal investigator, Breast Cancer Center, University Hospital Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03928210
- Sponsor's protocol ID
- 2019-00673; sp19Kurzeder
- Other IDs
- 2019
- Status last verified
- Dec 2023
- First submitted
- 23 Apr 2019
- Last updated
- 13 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kurzeder C, Nguyen-Strauli BD, Krol I, Ring A, Castro-Giner F, Nuesch M, Asawa S, Zhang YW, Budinjas S, Gvozdenovic A, Vogel M, Kohler A, Grasic Kuhar C, Schwab FD, Heinzelmann-Schwarz V, Weber WP, Rochlitz C, Vorburger D, Frauchiger-Heuer H, Witzel I, Wicki A, Kuster GM, Vetter M, Aceto N. Digoxin for reduction of circulating tumor cell cluster size in metastatic breast cancer: a proof-of-concept trial. Nat Med. 2025 Apr;31(4):1120-1124. doi: 10.1038/s41591-024-03486-6. Epub 2025 Jan 24.
PubMed 39856336
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Digoxin on Clusters of Circulating Tumor Cells (CTCs) in Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT03928210
- Acronym / sponsor ID
- 2019-00673; sp19Kurzeder
- Conditions
- Breast Cancer, Circulating Tumor Cells (CTCs)
- Keywords
- cluster of circulating tumor cells (CTCs), cardiac glycosides, digoxin
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Collaborators
- ETH Zurich - The Aceto Lab
- Study start
- 8 Jul 2020 (actual)
- Primary completion
- 1 Dec 2023 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 26 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This single arm therapeutic exploratory study of digoxin in patients with advanced or metastatic breast cancer investigates whether cardiac glycosides are able to disrupt CTC clusters in breast cancer patients.
Detailed description
Circulating tumor cells (CTCs) are considered to be precursors of metastasis in various cancer types and are found in the blood of cancer patients as single CTCs and CTC clusters, with the latter featuring a higher ability to seed metastasis.
CTC cluster share several properties that commonly feature stem cell biology which drive metastases formation. Preclinical data shows that CTC clusters can be disaggregated into single cells by the treatment with cardiac glycosides such as digoxin. This single arm therapeutic exploratory study of digoxin in patients with advanced or metastatic breast cancer investigates whether cardiac glycosides are able to disrupt CTC clusters in breast cancer patients.
Patients with advanced or metastatic breast cancer in whom CTC clusters could be identified will receive an individualized daily maintenance dose of digoxin adapted to their kidney function. Blood samples for analyses of digoxin serum level and mean CTC cluster size will be drawn at specified time points.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients with at least one CTC cluster (if homotypic ≥ 2 CTCs, if heterotypic ≥ 1 CTC and ≥ 1 white blood cell (WBC)) at screening entered the treatment phase. During treatment phase, patients received a daily maintenance dose of digoxin for a total of seven days, with a digoxin target level of ≥ 0.7 ng/ml in serum during treatment. Blood draws for capture and enumeration of CTCs and CTC clusters were obtained on day 0 (pre- and 2 hours post digoxin), day 3 and day 7. Regular study visits included clinical and laboratory assessments such as vital signs, electrocardiogram (ECG), serious adverse events (SAE), and digoxin serum levels on day 0 and 7.
| Arm | Type | Receives |
|---|---|---|
| Digoxin | Experimental | Drug: DigoxinDigoxin 0.125 mg or 0.25 mg administered once daily for 7 days or until symptoms of toxicity Generic e.g. DIGOXIN Juvisé or Lenoxin Mite |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Informed Consent as documented by signature
- Diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease not amenable to resection, radiation therapy or systemic therapy with curative intent
- Adequate organ and marrow function
Key exclusion criteria (19 listed)
- Patients on treatment with digoxin or digitoxin
- Patients with atrial fibrillation or atrial flutter
- Ventricular Fibrillation or ventricular tachycardia,
- Atrioventricular heart block 2nd or 3rd degree, sick sinus syndrome or sinus bradycardia,
- Wolff-Parkinson-White Syndrome
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 |
|---|---|---|
| DigoxinAlso: Lenoxin Mite, DIGOXIN JuviséPatients will receive a daily maintenance dose of digoxin. The daily dose of digoxin will be calculated according to the renal function and the target serum digoxin concentration and applied in an adjusted regimen based on the availability of 0.125 mg and 0.25 mg pills in the morning (before 10 am). Blood samples for analyses of mean CTC cluster size will be drawn at screening, on day 0 (2 hrs after first oral intake), on day 3 and on day 7. Depending on the digoxin serum level maintenance therapy with digoxin will be continued up to 3 weeks if the digoxin serum level on day 7 or day 14 is below 0.70 ng/ml. For the third week of maintenance therapy individual dose adjustments will be carried out as needed. | Drug | Digoxin |
Primary outcome
Change in mean CTC cluster size (in ng/ml)
Time frame: Blood samples drawn at Screening, on day 0 (2 hours after first oral intake of digoxin), on day 3, on day 7, on day 10, on day 14, on day 17 and on day 21 after first oral intake of digoxin
mean CTC cluster size (in patients with a digoxin serum level above 0.7 ng/ml) after treatment will be compared to mean CTC-cluster size before treatment
2 secondary outcomes
Change in mean CTC cluster number
Time frame: Blood samples drawn at Screening, on day 0 (2 hours after first oral intake of digoxin), on day 3, on day 7, on day 10, on day 14, on day 17 and on day 21 after first oral intake of digoxin
Average time to dissolution of CTC Clusters (in days)
Time frame: Blood samples drawn at Screening, on day 0 (2 hours after first oral intake of digoxin), on day 3, on day 7, on day 10, on day 14, on day 17 and on day 21 after first oral intake of digoxin
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2023.
- Derived from this study: PubMed 39856336Kurzeder C, Nguyen-Strauli BD, Krol I, Ring A, Castro-Giner F, Nuesch M, Asawa S, Zhang YW, Budinjas S, Gvozdenovic A, Vogel M, Kohler A, Grasic Kuhar C, Schwab FD, Heinzelmann-Schwarz V, Weber WP, Rochlitz C, Vorburger D, Frauchiger-Heuer H, Witzel I, Wicki A, Kuster GM, Vetter M, Aceto N. Digoxin for reduction of circulating tumor cell cluster size in metastatic breast cancer: a proof-of-concept trial. Nat Med. 2025 Apr;31(4):1120-1124. doi: 10.1038/s41591-024-03486-6. Epub 2025 Jan 24.
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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.
Christian Kurzeder, PD Dr. med principal investigator
Breast Cancer Center, University Hospital Basel
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Digoxin in people with Breast Cancer and Circulating Tumor Cells (CTCs), run by University Hospital, Basel, Switzerland at 3 sites in Switzerland.
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 3 inclusion and 19 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 13 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Switzerland. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 mean CTC cluster size (in ng/ml) (time frame: Blood samples drawn at Screening, on day 0 (2 hours after first oral intake of digoxin), on day 3, on day 7, on day 10, on day 14, on day 17 and on day 21 after first oral intake of digoxin). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03928210, which also lists 1 linked publication.
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 13 Dec 2023.