Digoxin Induced Dissolution of CTC Clusters

NCT03928210 | Completed Early Phase 1

• 1 other identifier: 2019-00673; sp19Kurzeder
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Breast Cancer; Circulating Tumor Cells (CTCs)

Keywords

cluster of circulating tumor cells (CTCs); cardiac glycosides; digoxin

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Change in mean CTC cluster number

  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)

  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

Study Arms (1)

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

Drug: Digoxin

Interventions

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.

Also known as: Lenoxin Mite, DIGOXIN Juvisé

Digoxin

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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,
• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• ETH Zurich - The Aceto Lab: collaborator

Study Sites (3)

Kantonspital Baselland (KSBL)

Liestal, Basel-Landschaft, 4410, Switzerland

Location

Breast Cancer Center, University Hospital Basel

Basel, 4031, Switzerland

Location

University Hospital Zurich (USZ)

Zurich, 8091, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 39856336 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplastic Cells, Circulating

Interventions

Digoxin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Christian Kurzeder, PD Dr. med

  Breast Cancer Center, University Hospital Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 23, 2019
• First Posted: April 26, 2019
• Study Start: July 8, 2020
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: December 13, 2023

Record last verified: 2023-12

Locations

CH (3)