To compare the plasma concentration of edoxaban in women with breast cancer before and during treatment with tamoxifen.
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
a comparison between day 4 and 36 of edoxaban area under the plasma
concenctration curve (AUC),maximum concentration (Cmax and several other
coagulation, pharmacokinetic and pharmacodynamic parameters.
Secondary outcome
NVT
Background summary
Edoxaban is an oral direct factor Xa inhibitor which is widely used in patients
with venous thromboembolism (VTE) or non-valvular atrial fibrillation.
Recently, this agent has been shown to be non-inferior to low-molecular-weight
heparin (LMWH) to prevent recurrent VTE in cancer patients. Edoxaban is also a
substrate for P-glycoprotein (P-gp), a protein that excretes certain
xenobiotics into the urine, faeces, and bile. Tamoxifen, an anti-estrogen drug
used as adjuvant treatment in breast cancer patients, is a known P- gp
inhibitor. Therefore, concomitant use of tamoxifen can potentially increase
plasma levels of edoxaban and thereby increase the risk of bleeding. In this
study, the effect of tamoxifen on the pharmacokinetics of edoxaban will be
evaluated.
Study objective
To compare the plasma concentration of edoxaban in women with breast cancer
before and during treatment with tamoxifen.
Study design
An open-label, single-sequence crossover study
Intervention
Twenty-six breast cancer patients who are scheduled for adjuvant or palliative
treatment with tamoxifen, will be given edoxaban 60 mg once daily for 4 days.
On day 5, edoxaban will be stopped and tamoxifen therapy started. When
steady-state of tamoxifen is reached after 28 days, edoxaban 60 mg once daily
is given for 4 days concomitantly with ongoing tamoxifen therapy. At the fourth
day of both edoxaban treatment periods, 4 blood samples (at 0, 1, 2, and 3
hours after ingestion) and one blood sample randomly taken in the time period 4
* 8 hours after ingestion will be collected.
Study burden and risks
Patients will be seen in the hospital for inclusion and two times for a series
of blood withdrawal on day 4 and 36. On days 4 and 36, patients have to be in
the hospital for 3 hours. During these days, patients will get a venous cannula
from which 4 blood samples will be taken per day over a time period of 3 hours.
One sample will be obtained 4 to 8 hours aftere ingestion of edoxaban. Total
volume of blood withdrawn is maximum 50.7 ml. In this study, patients will use
edoxaban, an anticoagulant drug. Patients may experience side effects of
medication, such as hematomas. Based on previous studies with edoxaban, it is
estimated that there is an individual risk of bleeding of 0.06% during this
study. There is no individual benefit from participating in this study.
However, the results may have clinical impact, because in patients with breast
cancer, tamoxifen is the mainstay of adjuvant treatment, often for a period of
5 years, where patients may suffer from VTE. Therefore, information on the
safety of this combination is important.
van Riebeeckweg 212
Hilversum 1213XZ
NL
van Riebeeckweg 212
Hilversum 1213XZ
NL
Listed location countries
Age
Inclusion criteria
-Women with breast cancer who will start with tamoxifen
-Age >18
Exclusion criteria
- Inability to provide informed consent
- Inherited bleeding disorder (e.g. von Willebrand disease)
- Major bleeding16 or clinically relevant non-major bleeding17 in the past 3
months
- History of intracranial bleeding
- Gastric or duodenal ulcer in the past 5 years
- Uncontrolled blood pressure with systolic pressure >180 mmHg
- Use of antiplatelet or anticoagulant therapy
- Chronic NSAID use
- Major surgery in the past 3 weeks (surgery which penetrates and exposes a
body cavity or
produces substantial impairment of physical function)
- Pregnancy, puerperium, or current breast feeding
- Use of strong P-gp inhibitors or inducers (see appendix B)
- Brain metastases
- Use of chemotherapy in the past 7 days or in the upcoming 32 days
- AST or ALT >3x of the upper limit in the past 7 days
- Liver cirrhosis Child Pugh A, B, or C
- Creatinine clearance of <50mL/min calculated with the Cockcroft and Gault
formula in the past
7 days
- Body weight <60kg
- Platelet count <50,000/mL in the past 7 days
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-004450-24-NL |
| CCMO | NL68239.018.18 |