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Genotype and Phenotype Guided Supplementation of TAMoxifen Standard Therapy With ENDOXifen in Breast Cancer Patients

NCT03931928 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 356

Last updated 2021-09-17

No results posted yet for this study

Summary

In hormone-receptor positive breast cancer or DCIS (ductal carcinoma in situ) tamoxifen remains an important treatment option for patients before menopause and those patients after menopause who cannot be treated with aromatase-inhibitors. Nonetheless, a considerable amount of patients suffer a relapse of their cancer while on treatment with tamoxifen. Tamoxifen is a drug that is metabolized to a variety of compounds by the human liver, and the most important antihormonally active metabolite is called (Z)-Endoxifen. It is known that patients who have a reduced or absent activity of the drug-metabolizing enzyme CYP2D6 have lower levels of (Z)-Endoxifen. Furthermore, it has been observed that patients on tamoxifen therapy who have absent CYP2D6 activity are at a 2-fold increased risk for disease recurrence, and patients with lower CYP2D6 compared to patients with normal CYP2D6 activity still have a 1.4-fold increased risk for disease recurrence.

This trial will include patients who are already on tamoxifen therapy for at least 3 months and is designed to show that in patients with absent or low CYP2D6 activity, (Z)-Endoxifen supplementation - that is giving (Z)-Endoxifen in addition to tamoxifen for the study period of 42 days - can increase blood levels of (Z)-Endoxifen to therapeutic concentrations. It is planned to included 504 patients in this blinded, randomized trial, which will have a placebo group (receiving no (Z)-Endoxifen) and two intervention groups that will receive 0, 1.5 or 3 mg (Z)-Endoxifen depending on their CYP2D6 genetics or their (Z)-Endoxifen levels at the start of the study.

The trial is not designed to evaluate outcome measures (that is recurrence or survival rates) of (Z)-Endoxifen supplementation in tamoxifen treated patients, but will document the safety of the combined administration of tamoxifen and (Z)-Endoxifen.

Conditions

Interventions

DRUG

(Z)-Endoxifen supplementation according to genotype

Group 2: CYP2D6 genotype predicted intermediate metabolizer receive 1.5 mg, poor metabolizer receive 3 mg (Z)-Endoxifen and extensive or ultrarapid metabolizer receive 0 mg endoxifen (Placebo)

DRUG

(Z)-Endoxifen supplementation according to plasma levels

Group 3: Patients will receive (Z)-endoxifen according to (Z)-endoxifen steady state plasma concentrations (phenotype) at screening (i.e. ≤ 15 nM receive 3 mg, \> 15 and ≤ 25 nM receive 1.5 mg (Z)-Endoxifen and \> 25 nM receive 0 mg (Placebo)

Sponsors & Collaborators

  • Robert Bosch Gesellschaft für Medizinische Forschung mbH (RBMF)

    lead OTHER

Principal Investigators

  • Matthias Schwab, Prof. Dr. · Margarete Fischer-Bosch-Institute of Clinical Pharmacology

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
FEMALE
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-09-10
Primary Completion
2021-05-03
Completion
2021-05-03

Countries

  • Germany

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03931928 on ClinicalTrials.gov