Predicting an Accurate Tamoxifen Dose: a Feasibility Study in Patients With Hormone Sensitive Breast Cancer

NL81896.078.22

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.

2022-11-01

2023-12-31

2024-02-28

Recruiting

Early phase I

100

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Non-randomized, single-center, single-arm, MIPD intervention study', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'One blood sample will be taken blindly and will be measured after the end of follow-up.'}}, 'enrollmentInfo': {'count': 100, 'type': 'ESTIMATED'}}

2023-11-01