E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Breast cancer |
borstkanker |
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E.1.1.1 | Medical condition in easily understood language |
breast cancer |
borstkanker |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the Area under the curve (AUC) of endoxifen in patients with breast cancer treated with tamoxifen with and without green tea. |
De AUC van endoxifen in patienten met borstkanker vergelijken wanneer ze worden behandeld met tamoxifen met en zonder thee. |
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E.2.2 | Secondary objectives of the trial |
1. To compare the Area under the Curve (AUC) of tamoxifen in patients with breast cancer treated with tamoxifen with and without green tea. 2. To compare other tamoxifen 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 green tea. 3. To evaluate the incidence and severity of side-effects of treatment with tamoxifen in absence and presence of green tea.
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1. De AUC van tamoxifen in patienten met borstkanker vergelijken wanneer ze worden behandeld met tamoxifen met en zonder groene thee. 2. De overige farmacokinetische parameters van tamoxifen en endoxifen bepalen (nl. klaring, maximale concentratie (Cmax), minimale concentratie (Ctrough), tijd tot maximale concentratie (tmax) en halfwaardetijd (t1/2). In patienten met borstkanker behandeld met tamoxifen met en zonder groene thee. 3. De incidentie en ernst van bijwerkingen van de behandeling met tamoxifen in de aan- en afwezigheid van groene thee |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. (see Appendix C) 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 7. Endoxifen trough concentration of 16 nM
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1. Leeftijd boven de 18 jaar 2. patienten met borstkanker waarvoor behandeling met tamoxifen gedurende ten minste 3 maanden 3. WHO performance status kleiner of gelijk aan 1 4. bereid tot tekenen informed consent 5. bereid om af te zien van gebruik van sterke CYP3A4, CYP2D6, CYP2C9/2C19, UGT and P-gp inhibitors of inducers, kruiden of dieetsupplementen of andere OTC medicatie naast paracetamol 6 adequate orgaanfunctie - ALAT en ASAT <5.0 upper limit of normal (ULN) - bilirubine <1.5 (ULN) - GFR > 30 ml/min/1.73 m2
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating patients 2. Patients with known impaired drug absorption (e.g. gastrectomy and achlorhydria) 3. Patients with an active gastric ulcer 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<30 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.
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1. zwangere of lacterende patienten 2. patienten met bekende absorptieproblemen 3. patienten met een actieve maagulcer 4. bekende serieuze of onstabiele medische condities waarvoor medicatie nodig is 5. een CYP2D6 poor metabolizer of ultra rapid metabolizer fenotype |
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare the Area under the curve (AUC) of endoxifen in patients with breast cancer treated with tamoxifen with and without green tea. |
De AUC van endoxifen in patienten met borstkanker vergelijken wanneer ze worden behandeld met tamoxifen met en zonder thee. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Last visit last patient |
Laatste visite van de laatste patient |
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E.5.2 | Secondary end point(s) |
1. To compare the Area under the Curve (AUC) of tamoxifen in patients with breast cancer treated with tamoxifen with and without green tea. 2. To compare other tamoxifen 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 green tea. 3. To evaluate the incidence and severity of side-effects of treatment with tamoxifen in absence and presence of green tea.
|
1. De AUC van tamoxifen in patienten met borstkanker vergelijken wanneer ze worden behandeld met tamoxifen met en zonder groene thee. 2. De overige farmacokinetische parameters van tamoxifen en endoxifen bepalen (nl. klaring, maximale concentratie (Cmax), minimale concentratie (Ctrough), tijd tot maximale concentratie (tmax) en halfwaardetijd (t1/2). In patienten met borstkanker behandeld met tamoxifen met en zonder groene thee. 3. De incidentie en ernst van bijwerkingen van de behandeling met tamoxifen in de aan- en afwezigheid van groene thee |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Last visit last patient |
Laatste visite van de laatste patient |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |