Tamoxifen Prediction Study in Patients With ER+ Breast Cancer

• Status: Not yet recruiting
• Trial end date: 2023-07-01
• Target enrollment: 0
• Participant gender: Female

Summary

Adjuvant treatment with tamoxifen is the standard of care for women with estrogen receptor positive (ER+) breast cancer. Tamoxifen is converted to endoxifen, its active metabolite, via CYP2D6 enzymes. The literature states that an endoxifen concentration of at least 16 nmol/L is needed to produce a therapeutic effect (4). Therapeutic Drug Monitoring (TDM) has been proven to be a successful technique to reach the 16 nmol/L endoxifen threshold after 6 months. However, in general TDM can only be used when a drug is in steady-state, which for endoxifen is reached after 3 months for normal metabolizers. For poor- and intermediate metabolizers, the time until steady-state is presumably even longer. This could possibly result in undertreatment within the first 3 to 6 months of tamoxifen treatment. In this study, model-informed precision dosing (MIPD) will be used to counter this problem. The Pharmacokinetic-model, which is used for MIPD, includes CYP2D6 genotype, co-medication, age, body height, BMI and CYP2D6/CYP3A inhibitor use to predict a patient tailored dose. Using MIPD, our aim is to decrease the proportion of patients that are undertreated within the first three months of tamoxifen treatment.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Erasmus Medical Center
• Treatments: Tamoxifen

Criteria

Inclusion Criteria:

1. Age ≥ 18 years;

2. WHO Performance Status ≤ 1 (see Appendix A);

3. Patients with primary breast cancer, with a prescription for adjuvant tamoxifen treatment;

4. Willing to abstain from strong and moderate CYP3A4 or CYP2D6 inhibitors or inducers, according to: CYTOCHROME P450 DRUG INTERACTION TABLE - Drug Interactions (iu.edu);

5. Able and willing to sign the Informed Consent Form;

6. Able and willing to undergo blood sampling for PK analysis.

Exclusion Criteria:

1. Patients with known alcoholism, drug addiction and/or psychiatric or physiological condition which in the opinion of the investigator would impair treatment compliance;

2. > 2 weeks of tamoxifen treatment before inclusion;

3. Patients who's endoxifen levels have been used for therapeutic drug monitoring in the past.