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The influence of morning versus evening administration on tamoxifen pharmacokinetics.


- candidate number12890
- NTR NumberNTR3473
- ISRCTNISRCTN wordt niet meer aangevraagd.
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR12-jun-2012
- Secondary IDs2012-091 METC Erasmus MC
- Public TitleThe influence of morning versus evening administration on tamoxifen pharmacokinetics.
- Scientific TitleThe influence of morning versus evening administration on tamoxifen pharmacokinetics.
- ACRONYM
- hypothesisTamoxifen pharmacokinetics may be influenced by circadian rhythm. Endoxifen exposure may differ between morning administration of tamoxifen and administration in the evening.
- Healt Condition(s) or Problem(s) studiedBreast cancer, Tamoxifen
- Inclusion criteria1. Histological or cytological confirmed diagnosis of breast cancer, for which treatment with tamoxifen is indicated;
2. Use of tamoxifen for at least 4 weeks and willing to continue the treatment until the end of the study;
3. Age > 18 years;
4. WHO performance ≤ 1;
5. Written informed consent;
6. Adequate renal and hepatic functions;
7. Adequate hematological blood counts;
8. No chemotherapy or radiotherapy within the last 4 weeks before start.
- Exclusion criteria1. Pregnant or lactating patients;
2. Serious illness or medical unstable condition requiring treatment, symptomatic CNS metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent;
3. More than one tamoxifen dose per day (20 or 40 mg);
4. Non-compliance.
- mec approval receivedyes
- multicenter trialno
- randomisedno
- groupCrossover
- Type2 or more arms, non-randomized
- Studytypeintervention
- planned startdate 1-jul-2012
- planned closingdate1-jul-2013
- Target number of participants18
- InterventionsPatients will switch from administration of tamoxifen in the morning to administration in the evening or vice versa.
- Primary outcomeDetermine differences in tamoxifen pharmacokinetics during tamoxifen administration in the morning compared to administration in the evening.
- Secondary outcomeDetermine differences in adverse effects during tamoxifen administration in the morning compared to administration in the evening.
- Timepoints1. Prior to the study: Informed consent;
2. Tamoxifen administration in the morning/evening* for at least 4 weeks;
3. Pharmacokinetic sampling during a 24-hour (clinical) period;
4. Patients will switch to administration of tamoxifen in the morning/evening*;
5. Tamoxifen administration in the morning/evening* for at least 4 weeks;
6. Pharmacokinetic sampling during a 24-hour (clinical) period;
7. Evaluation of adverse effects during the study.

* = dependent on group.

Pharmacokinetic parameters (AUC, Cmax, Tmax) will be evaluated and compared between morning and evening administration.
- Trial web siteN/A
- statusplanned
- CONTACT FOR PUBLIC QUERIES Lisette Binkhorst
- CONTACT for SCIENTIFIC QUERIESMD PhD Ron H.J. Mathijssen
- Sponsor/Initiator Erasmus Medical Center, Daniel den Hoed Cancer Center
- Funding
(Source(s) of Monetary or Material Support)
Erasmus Medical Center, Daniel den Hoed Cancer Center
- PublicationsN/A
- Brief summaryTamoxifen is still an important and effective drug for the treatment of breast cancer. However, tamoxifen has to be converted to the (most abundant) active metabolite endoxifen. CYP-mediated metabolism plays an important role in the metabolism of tamoxifen into endoxifen. CYP-enzyme activity, biliary excretion and expression of transporters are suggested to be influenced by a circadian rhythm. This suggests that tamoxifen pharmacokinetics may be influenced by circadian rhythm and time of tamoxifen administration may influence endoxifen concentrations.
In this study we will investigate the influence of morning versus evening administration on the pharmacokinetics of tamoxifen.
Patients who are treated with tamoxifen will be included in this trial; nine patients who use tamoxifen in the morning and nine patients who use tamoxifen in the evening. Patients will switch from administration in the morning to administration of tamoxifen in the evening (or vice versa). During both periods, patients will undergo a 24-hour pharmacokinetic sampling period. Blood samples will be analysed by a validated LC-MS/MS method. The differences in pharmacokinetic parameters will be statistically evaluated using a paired Student's t-test or Wilcoxon rank sum test in case of a non-gaussian population.
- Main changes (audit trail)01-Apr-2013: Due to an amendment, changes have been made to the protocol, which are listed below - NM

Hypothesis:
Amendment: Tamoxifen pharmacokinetics may be influenced by circadian rhythm. Endoxifen exposure may differ between morning administration of tamoxifen and administration in the afternoon and evening.
Interventions:
Amendment: Patients will switch for a second time from tamoxifen administration in the morning/evening to administration in the afternoon.
Primary outcome:
Amendment: Determine differences in tamoxifen pharmacokinetics during tamoxifen administration in the morning, afternoon and evening.
Secondary outcome:
Amendment: Determine differences in adverse effects during tamoxifen administration in the morning compared to administration in the afternoon and evening.
Timepoints: Amendment:
1. Patients will switch to administration of tamoxifen in the afternoon;
2. Tamoxifen administration in the afternoon (~ 1.00 PM) for at least 4 weeks;
3. Pharmacokinetic sampling during a 24-hour (clinical) period.
Amendment: Pharmacokinetic parameters (AUC, Cmax, Tmax) will be evaluated and compared between morning, afternoon and evening administration.
Brief Summary:
Amendment: To observe whether tamoxifen pharmacokinetics differ between morning (8 a.m.), afternoon (1 p.m.) and evening (8 p.m.) dosing, possibly reaching higher levels of tamoxifen and active metabolites after dosing at 1 p.m., a third time-point (1 p.m.) of tamoxifen administration will be included in the study (to investigate the effects on pharmacokinetics).
- RECORD12-jun-2012 - 1-apr-2013


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