Digoxin Induced Dissolution of CTC Clusters

NCT ID: NCT03928210

Last Updated: 2023-12-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-08
• Study Completion Date: 2023-12-01

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.

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)

Keywords

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Digoxin

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

Group Type: EXPERIMENTAL

Digoxin

Intervention Type: 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.

Interventions

Digoxin

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.

Intervention Type: DRUG

Other Intervention Names

Lenoxin Mite; DIGOXIN Juvisé

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ETH Zurich - The Aceto Lab

UNKNOWN

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian Kurzeder, PD Dr. med

Role: PRINCIPAL_INVESTIGATOR

Breast Cancer Center, University Hospital Basel

Locations

Kantonspital Baselland (KSBL)

Liestal, Basel-Landschaft, Switzerland

Breast Cancer Center, University Hospital Basel

Basel, , Switzerland

University Hospital Zurich (USZ)

Zurich, , Switzerland

Countries

Switzerland

References

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.

Reference Type: DERIVED

PMID: 39856336 (View on PubMed)

Other Identifiers

2019-00673; sp19Kurzeder

Identifier Type: -

Identifier Source: org_study_id