NCT03931928: TAMENDOX

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

Completed Phase 2 Last updated 17 September 2021

What this trial tests

Phase 2 trial testing (Z)-Endoxifen supplementation according to genotype in Breast Cancer in 356 participants. Completed in 3 May 2021.

Timeline

10 September 2019

Primary endpoint
3 May 2021

3 May 2021

Quick facts

Lead sponsor	Robert Bosch Gesellschaft für Medizinische Forschung mbH (RBMF)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	356
Start date	10 September 2019
Primary completion	3 May 2021
Estimated completion	3 May 2021
Sites	40 locations across Germany

Drugs / interventions tested

• (Z)-Endoxifen supplementation according to genotype — full drug profile →
• (Z)-Endoxifen supplementation according to plasma levels — full drug profile →

Conditions studied

• Breast Cancer — all drugs for Breast Cancer →
• DCIS — all drugs for DCIS →

Sponsor

Robert Bosch Gesellschaft für Medizinische Forschung mbH (RBMF) — full company profile →

Who can join

18 and older, female only, with Breast Cancer or DCIS. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Therapeutic Drug Monitoring of Endoxifen for Tamoxifen Precision Dosing: Feasible in Patients with Hormone-Sensitive Breast Cancer.
   Braal CL, Jager A, Hoop EO, Westenberg JD, et al · · 2022 · cited 28× · PMID 34786650 · DOI 10.1007/s40262-021-01077-z
2. Integrated Data Analysis of Six Clinical Studies Points Toward Model-Informed Precision Dosing of Tamoxifen.
   Klopp-Schulze L, Mueller-Schoell A, Neven P, Koolen SLW, et al · · 2020 · cited 24× · PMID 32296331 · DOI 10.3389/fphar.2020.00283