Digoxin Induced Dissolution of CTC Clusters

University Hospital Basel

Status and phase

Completed

Early Phase 1

Conditions

Circulating Tumor Cells (CTCs)

Breast Cancer

Treatments

Drug: Digoxin

Study type

Interventional

Funder types

Other

Identifiers

NCT03928210

2019-00673 sp19Kurzeder;

Details and patient eligibility

About

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.

Full 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.

Enrollment

58 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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