Digoxin Induced Dissolution of CTC Clusters

Early Phase 1

Completed

• Conditions: Breast Cancer; Circulating Tumor Cells (CTCs)
• Interventions: Drug: Digoxin

• Registration Number: NCT03928210
• Lead Sponsor: University Hospital, Basel, Switzerland

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.

Study Timeline

• Study First Submitted: 2019-04-23
• Study First Submitted QC: 2019-04-23
• Study First Posted: 2019-04-26
• Study Start: 2020-07-08
• Status Verified: 2023-12
• Primary Completion: 2023-12-01
• Study Completion: 2023-12-01
• Last Update Submitted: 2023-12-06
• Last Update Posted: 2023-12-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 58

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Digoxin	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

Primary Outcome Measures

Name	Time	Method
Change in mean CTC cluster size (in ng/ml)	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

Secondary Outcome Measures

Name	Time	Method
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	average time to dissolution of CTC clusters
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	number of CTC-clusters before and after treatment will be compared

Trial Locations

Locations (3)

University Hospital Zurich (USZ); 🇨🇭 Zürich, Switzerland

Breast Cancer Center, University Hospital Basel; 🇨🇭 Basel, Switzerland

Kantonspital Baselland (KSBL); 🇨🇭 Liestal, Baselland, Switzerland