Optimizing endoxifen concentration through the induction of CYP3A4, CYP2C and CYP2D6 mediated tamoxifen metabolism

Completed

• Conditions: Breast cancer; 10006291

• Registration Number: NL-OMON38337
• Lead Sponsor: Erasmus MC, Universitair Medisch Centrum Rotterdam

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 12

Inclusion Criteria

• Histological or cytological confirmed diagnosis of (invasive) breast cancer, for which treatment with tamoxifen monotherapy is indicated (to be evaluated by the treating physician);
• Use of tamoxifen monotherapy for at least 4 weeks (to guarantee steady-state) and willing to continue the treatment until the end of the study;
• Age >18 years;
• WHO performance <1;
• Adequate renal and hepatic functions (serum creatinin < 1.25x upper limit of normal (ULN), total bilirubin < 1.25xULN; alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) < 2.5x ULN, in case of liver metastasis < 5 ULN; alkaline phosphatase (AF) < 5xULN);
• Adequate hematological blood counts (absolute neutrophil count (ANC) > 1.5 x 109/L, platelets > 100 x 1012/L);
• Written informed consent;
• No chemotherapy within the last 4 weeks before start;
• No radiotherapy within the last 4 weeks before start;
• No concurrent (over the counter) medication or (herbal) supplements known to induce or inhibit CYP2D6, CYP2C, CYP3A4 and/or P-glycoprotein;
• Abstain from grapefruit, grapefruit juice, herbal dietary supplements, and herbal tea during the study.

Exclusion Criteria

• Pregnant or lactating patients;
• Impossibility to take oral drugs;
• 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;
• Contra-indications for dextromethorphan use;
• Use of medications or dietary supplements known to induce or inhibit CYP2D6, CYP2C, CYP3A4 and/or P-glycoprotein;
• Unwillingness to abstain from grapefruit (juice), (herbal) dietary supplements, herbals, over-the-counter medication (except for paracetamol and ibuprofen) and other drugs known to seriously interact with CYP3A during the study period;
• Non-compliance

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Amendment:<br /><br>N.A. (cancelled)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Amendment:<br /><br>- To validate the previously developed dextromethorphan phenotyping test (AUC<br /><br>0-6h).</p><br>