The POWER Trial: Personalised Dose Optimisation With Adjuvant Tamoxifen Therapy in Breast cancER

Karolinska Institute

Status and phase: Not yet enrolling; Phase 3

Conditions: Breast Cancer; Adjuvant Drug Therapy

Treatments: Drug: Standard adjuvant therapy of tamoxifen; Drug: Individual dose of tamoxifen

Study type: Interventional

Funder types: Other

Identifiers

NCT07502820

2025-522240-40-00

Details and patient eligibility

About

In Sweden, approximately 7000 women are diagnosed with hormone-sensitive breast cancer annually. According to international and national guidelines, most of these women are recommended anti-hormonal therapy for five to ten years to improve prognosis. Tamoxifen, one of the most widely used anti-hormonal agents globally, reduces the risk of recurrence by 40% and breast cancer mortality by 30%.

Tamoxifen is a pro-drug that undergoes hepatic metabolism to form endoxifen and other active metabolites. Variability in metabolic capacity affects therapeutic efficacy: poor metabolisers produce insufficient endoxifen and other active metabolites, risking therapeutic failure, while ultrarapid metabolisers generate excessive amounts, leading to intolerable adverse effects. Today, 30-50% of patients discontinue treatment prematurely due to severe side effects, resulting in suboptimal outcomes.

Currently, tamoxifen is uniformly prescribed at a daily dose of 20 mg, and so far, no clinical trials have tested whether individualised dosing could enhance adherence and improve survival outcomes. The primary objective is to evaluate whether individualised tamoxifen dosing reduces discontinuation rates and enhances patient outcomes in breast cancer treatment.

Enrollment: 1,100 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with primary breast cancer, recommended for adjuvant tamoxifen treatment with or without concomitant goserelin
• Premenopausal or perimenopausal, defined according to SOC for therapy decision
• Eastern Cooperative Oncology Group (ECOG) WHO Performance Scale 0 - 2
• Participants must use non-hormonal contraception during the trial.

Exclusion criteria

• Previous use of tamoxifen, endoxifen, or aromatase inhibitors.
• Previous medical history of:

Deep venous thrombosis or pulmonary embolism; bleeding disorder or coagulopathy; macular disorders, retinal disorders, severe cataract or glaucoma.

• Current use of warfarin.
• Not willing to abstain from strong and moderate CYP2D6 inhibitors or CYP3A4 inducers during the tamoxifen treatment
• Current pregnancy, breastfeeding, or already at start of tamoxifen planning to become pregnant within the next two years
• Use of systemic menopausal hormonal therapy (MHT).
• Prior invasive malignancy during the last five years. Prior or current in situ cancers are allowed.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,100 participants in 2 patient groups

Individualised care with tamoxifen dose adjustments.

Experimental group

Description:

Patients randomised to individualised care will have their dose adjusted according to an algorithm based on patient reported side effects and the concentration of (z)-endoxifen in blood.

Treatment:

Drug: Individual dose of tamoxifen

Standard-of-care with the standard tamoxifen dose of 20 mg orally once per day.

Active Comparator group

Description:

In the control arm, each subject undergoes treatment with the standard dose 20 mg tamoxifen daily by oral intake of one tablet, with no possibilty of dose adjustment during the trial.

Treatment:

Drug: Standard adjuvant therapy of tamoxifen