Tamoxifen Prediction Study in Patients With ER+ Breast Cancer

NCT05525481 | Unknown Phase 4

• 1 other identifier: NL81896.078.22
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

ER+ Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Primary endpoint

  The primary endpoint is the proportion of patients who reach an endoxifen level of 16 nmol/L or higher.

  Begin-end (3 months)

Secondary Outcomes (4)

• Secondary outcome 1

  Begin-end (3 months)

• Secondary outcome 2

  Begin-end (3 months)

• Secondary outcome 3

  Begin-end (3 months)

• Secondary outcome 4

  Begin-end (3 months)

Study Arms (1)

Intervention arm

EXPERIMENTAL

This is a single-arm trial. We only have one experimental arm. The control arm will be provided by another study.

Drug: Tamoxifen

Interventions

Tamoxifen DRUG

Hormone therapy

Intervention arm

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Biological females.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years;
• WHO Performance Status ≤ 1 (see Appendix A);
• Patients with primary breast cancer, with a prescription for adjuvant tamoxifen treatment;
• Willing to abstain from strong and moderate CYP3A4 or CYP2D6 inhibitors or inducers, according to: CYTOCHROME P450 DRUG INTERACTION TABLE - Drug Interactions (iu.edu);
• Able and willing to sign the Informed Consent Form;
• Able and willing to undergo blood sampling for PK analysis.

You may not qualify if:

• Patients with known alcoholism, drug addiction and/or psychiatric or physiological condition which in the opinion of the investigator would impair treatment compliance;
• Patients who's endoxifen levels have been used for therapeutic drug monitoring in the past.

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus MC

Rotterdam, South Holland, 3065NB, Netherlands

RECRUITING

MeSH Terms

Interventions

Tamoxifen

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Central Study Contacts

Ruben van Nijnatten

CONTACT

0683995382; r.vannijnatten@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: One blood sample will be taken blindly and will be measured after the end of follow-up.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Non-randomized, single-center, single-arm, MIPD intervention study

Study Record Dates

• First Submitted: August 30, 2022
• First Posted: September 1, 2022
• Study Start: November 1, 2022
• Primary Completion: December 31, 2023
• Study Completion: February 28, 2024
• Last Updated: November 1, 2023

Record last verified: 2023-10

Locations

NL (1)