Digoxin Induced Dissolution of CTC Clusters

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Recruiting

CT.gov ID

NCT03928210

Collaborator

(none)

Enrollment

Location

Arm

22.8

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Circulating Tumor Cells (CTCs)	Drug: Digoxin	Early Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

9 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effect of Digoxin on Clusters of Circulating Tumor Cells (CTCs) in Breast Cancer Patients

Actual Study Start Date :

Jul 8, 2020

Anticipated Primary Completion Date :

May 1, 2022

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Digoxin	Drug: 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.

Arm

Intervention/Treatment

Experimental: Digoxin

Drug: 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.

Outcome Measures

Primary Outcome Measures

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

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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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