Study on the pharmacokinetic interaction between diclofenac and tamoxifen in patients with breast cancer. the DICLOTAM study

Phase 4

Withdrawn

Conditions: Hormone sensitieve breast cancer
10006291

Registration Number: NL-OMON48096

Lead Sponsor: Erasmus MC, Universitair Medisch Centrum Rotterdam

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 14

Inclusion Criteria

1. Age * 18 years
2. Patients with a confirmed diagnosis of primary or advanced breast cancer, who are on tamoxifen treatment for at least three months (steady state concentration).
3. WHO performance * 1 (see Appendix B)
4. Able and willing to sign the informed consent form prior to screening evaluations
5. Willing to abstain from strong CYP3A4, CYP2D6, CYP2C9/2C19, UGT and P-gp inhibitors or inducers, herbal or dietary supplements or other over-the-counter medication besides paracetamol.
6. Adequate organ function defined as:
- ALAT and ASAT <5.0 upper limit of normal (ULN)
- bilirubin <1.5 (ULN)
- GFR > 30 ml/min/1.73 m2
- Controlled thyroid dysfunction

Exclusion Criteria

1. Pregnant or lactating patients
2. Patients with known impaired drug absorption (e.g. gastrectomy and achlorhydria)
3. Patients with a history of (stomach) ulcers or gastric bleeding or hypersensitivity to NSAIDs.
4. Known serious illness or medical unstable conditions that could interfere with this study requiring treatment (e.g. HIV, hepatitis, Varicella zoster or herpes zoster, organ transplants, kidney failure (GFR<60 ml/min/1.73 m2), serious liver disease (e.g. severe cirrhosis), cardiac and respiratory diseases)
5. A CYP2D6 poor metabolizer or ultra-rapid metabolizer phenotype based on CYP2D6 genotyping outcome.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To investigate the interaction between diclofenac and tamoxifen; by comparing<br /><br>the Area under the curve (AUC) of endoxifen in patients with breast cancer<br /><br>treated with tamoxifen with and without diclofenac.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1. To compare the Area Under the Curve (AUC) of tamoxifen and<br /><br>endoxifen-glucuronide in patients with breast cancer treated with tamoxifen<br /><br>with and without diclofenac.<br /><br><br /><br>2. To compare other tamoxifen, endoxifen-glucuronide and endoxifen<br /><br>pharmacokinetic outcomes (i.e. clearance, maximum concentration (Cmax), minimal<br /><br>concentration (Ctrough) and time until maximum concentration (Tmax) and<br /><br>elimination half-life (T*)). Furthermore the endoxifen/endoxifen-glucuronide<br /><br>ratio in patients with breast cancer treated with tamoxifen with and without<br /><br>diclofenac.<br /><br><br /><br>3. To evaluate the incidence and severity of side-effects of treatment with<br /><br>tamoxifen in absence and presence of diclofenac.</p><br>