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Digoxin Induced Dissolution of CTC Clusters

Primary Purpose

Breast Cancer, Circulating Tumor Cells (CTCs)

Status
Active
Phase
Early Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
Digoxin
Sponsored by
University Hospital, Basel, Switzerland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring cluster of circulating tumor cells (CTCs), cardiac glycosides, digoxin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Kantonspital Baselland (KSBL)
  • Breast Cancer Center, University Hospital Basel
  • University Hospital Zurich (USZ)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Digoxin

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Change in mean CTC cluster number
number of CTC-clusters before and after treatment will be compared
Average time to dissolution of CTC Clusters (in days)
average time to dissolution of CTC clusters

Full Information

First Posted
April 23, 2019
Last Updated
July 11, 2023
Sponsor
University Hospital, Basel, Switzerland
Collaborators
ETH Zurich - The Aceto Lab
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1. Study Identification

Unique Protocol Identification Number
NCT03928210
Brief Title
Digoxin Induced Dissolution of CTC Clusters
Official Title
Effect of Digoxin on Clusters of Circulating Tumor Cells (CTCs) in Breast Cancer Patients
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 8, 2020 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
September 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland
Collaborators
ETH Zurich - The Aceto Lab

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Circulating Tumor Cells (CTCs)
Keywords
cluster of circulating tumor cells (CTCs), cardiac glycosides, digoxin

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Digoxin
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Digoxin
Other Intervention Name(s)
Lenoxin Mite, DIGOXIN Juvisé
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in mean CTC cluster size (in ng/ml)
Description
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
Time Frame
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 Outcome Measure Information:
Title
Change in mean CTC cluster number
Description
number of CTC-clusters before and after treatment will be compared
Time Frame
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
Title
Average time to dissolution of CTC Clusters (in days)
Description
average time to dissolution of CTC clusters
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian Kurzeder, PD Dr. med
Organizational Affiliation
Breast Cancer Center, University Hospital Basel
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kantonspital Baselland (KSBL)
City
Liestal
State/Province
Baselland
ZIP/Postal Code
4410
Country
Switzerland
Facility Name
Breast Cancer Center, University Hospital Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Facility Name
University Hospital Zurich (USZ)
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

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Digoxin Induced Dissolution of CTC Clusters

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