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| Name | Class |
|---|---|
| ETH Zurich - The Aceto Lab | UNKNOWN |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Digoxin | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in mean CTC cluster number | number of CTC-clusters before and after treatment will be compared | 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christian Kurzeder, PD Dr. med | Breast Cancer Center, University Hospital Basel | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kantonspital Baselland (KSBL) | Liestal | Basel-Landschaft | 4410 | Switzerland | ||
| Breast Cancer Center, University Hospital Basel |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39856336 | Derived | 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. |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009360 | Neoplastic Cells, Circulating |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D004077 | Digoxin |
| ID | Term |
|---|---|
| D004071 | Digitalis Glycosides |
| D002298 | Cardenolides |
| D002301 | Cardiac Glycosides |
| D002297 | Cardanolides |
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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.
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|
|
average time to dissolution of CTC clusters |
| 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 |
| Basel |
| 4031 |
| Switzerland |
| University Hospital Zurich (USZ) | Zurich | 8091 | Switzerland |
| D017437 |
| Skin and Connective Tissue Diseases |
| D009362 | Neoplasm Metastasis |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D013256 |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D006027 | Glycosides |
| D002241 | Carbohydrates |