Clinical trial NCT03928210: 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
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Breast Cancer
Circulating Tumor Cells (CTCs)
Keywords: cluster of circulating tumor cells (CTCs)
cardiac glycosides
digoxin
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: ETH Zurich - The Aceto Lab
First posted: 2019-04-26
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients with at least one CTC cluster (if homotypic ≥ 2 CTCs, if heterotypic ≥ 1 CTC and ≥ 1 white blood cell (WBC)) at screening entered the treatment phase. During treatment phase, patients received a daily maintenance dose of digoxin for a total of seven days, with a digoxin target level of ≥ 0.7 ng/ml in serum during treatment. Blood draws for capture and enumeration of CTCs and CTC clusters were obtained on day 0 (pre- and 2 hours post digoxin), day 3 and day 7. Regular study visits included clinical and laboratory assessments such as vital signs, electrocardiogram (ECG), serious adverse events (SAE), and digoxin serum levels on day 0 and 7.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in mean CTC cluster size (in ng/ml)
timeFrame: 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 outcomes:
measure: Change in mean CTC cluster number
timeFrame: 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
measure: Average time to dissolution of CTC Clusters (in days)
timeFrame: 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
Other outcomes:
Locations:
city: Liestal
country: Switzerland
facility: Kantonspital Baselland (KSBL)
state: Baselland
city: Basel
country: Switzerland
facility: Breast Cancer Center, University Hospital Basel
city: Zürich
country: Switzerland
facility: University Hospital Zurich (USZ)
Study officials:
affiliation: Breast Cancer Center, University Hospital Basel
name: Christian Kurzeder, PD Dr. med
role: PRINCIPAL_INVESTIGATOR
References: