Hormone positive breast cancer
Conditions
Interventions
Trade Name: tamoxifen
Pharmaceutical Form: Tablet
Trade Name: Probenecid
Pharmaceutical Form: Tablet
Sponsors
Erasmus MC Cancer Institute
Eligibility
Sex/Gender
All
Inclusion criteria
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. A CYP2D6 poor metabolizer or intermediate metabolizer phenotype 4. WHO performance = 1 5. Able and willing to sign the informed consent form prior to screening evaluations 6. 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. ( Appendix C) 7. Adequate kidney function defined as: GFR > 50 ml/min/1.73 m2 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating patients 2. Patients with known impaired drug absorption (e.g. gastrectomy and achlorhydria) 3. Use of drugs which may show an increased systemic exposure when taken concomitantly with probenecid e.g. methotrexate, penicillin, cephalosporin or chinolon antibiotics or NSAIDs. 4. Patients with known blood dyscrasias, porphyria, uric acid kidney stones or until an acute gouty attack has subsided. 5. 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<30 ml/min/1.73 m2), serious liver disease (e.g. severe cirrhosis), cardiac and respiratory diseases)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the Area under the curve (AUC) of endoxifen in patients with breast cancer treated with tamoxifen with and without probenecid. ;Secondary Objective: 1. To compare the Area under the Curve (AUC) of tamoxifen and endoxifen-glucuronide in patients with breast cancer treated with tamoxifen with and without probenecid. 2. To compare other tamoxifen, endoxifen-glucuronide and endoxifen pharmacokinetic outcomes (i.e. clearance, maximum concentration (Cmax), minimal concentration (Ctrough) and time until maximum concentration (tmax) and elimination half-life (t½)). Furthermore the endoxifen/endoxifen-glucuronide ratio will be determined in patients with breast cancer treated with tamoxifen with and without probenecid. 3. To evaluate the incidence and severity of side-effects of treatment with tamoxifen in absence and presence of probenecid. ;Primary end point(s): Main pharmacokinetic parameter to be determined will be Area Under the plasma-concentration time Curve (AUC) of endoxifen.;Timepoint(s) of evaluation of this end point: after 35 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To compare the Area Under the Curve (AUC) of tamoxifen and endoxifen-glucuronide in patients with breast cancer treated with tamoxifen with and without probenecid. 2. To compare other tamoxifen, endoxifen-glucuronide and endoxifen pharmacokinetic outcomes (i.e. clearance, maximum concentration (Cmax), minimal concentration (Ctrough) and time until maximum concentration (Tmax) and elimination half-life (T½)). in patients with breast cancer treated with tamoxifen with and without probenecid. 3. To evaluate the incidence and severity of side-effects of treatment with tamoxifen in absence and presence of probenecid.;Timepoint(s) of evaluation of this end point: End of the study | — |
Countries
Netherlands
Contacts
Public ContactR.H.J. Mathijssen
Erasmus MC Cancer Institute
Outcome results
None listed