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

NCT07502820 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 2025-522240-40-00
• Study Type: interventional
• Target: 1,100
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Breast Cancer; Adjuvant Drug Therapy

Keywords

Early-stage breast cancer; Adjuvant; Endocrine therapy; Tamoxifen; Therapeutic drug monitoring TDM; Precision medicine

Outcome Measures

Primary Outcomes (1)

• Discontinuation of tamoxifen.

  The primary outcome is discontinuation of tamoxifen. This will be declared when any of the following four criteria are satisfied: * Agreement between patient and doctor that the patient will discontinue tamoxifen. * Patient notifies doctor that she has discontinued tamoxifen. * Patient-reported tamoxifen tablet intake of zero tablets for 13 consecutive weeks. * Patient refuses dose of tamoxifen as recommended per protocol by their clinician.

  From enrollment to end of treatment at 60 months.

Secondary Outcomes (11)

• Patient reported outcomes.

  From enrollment to end of treatment at 60 months.

• Quality of life questionnaire

  From enrollment to end of treatment at 60 months.

• Concentration of circulation plasma metabolites

  From 3 months after treatment start to end of treatment at 60 months

• Invasive disease-free survival (iDSF)

  From enrollment to end of treatment at 60 months.

• Distant relapse-free survival (DRFS)

  From enrollment to end of treatment at 60 months.

Other Outcomes (2)

• Number of participants with genetic polymorphisms in germline DNA

  Blood collection at enrollment

• Number of biomarkers of potential use for therapeutic drug monitoring

  From enrollment to end of treatment at 60 months.

Study Arms (2)

Individualised care with tamoxifen dose adjustments.

EXPERIMENTAL

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.

Drug: Individual dose of tamoxifen

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

ACTIVE COMPARATOR

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.

Drug: Standard adjuvant therapy of tamoxifen

Interventions

Individual dose of tamoxifen DRUG

Each subject starts their treatment with the standard dose 20 mg tamoxifen daily by oral intake. During visits 2 (3 months), 3 (six months) and 4 (twelve months), the investigator will either let the patient remain on 20 mg tamoxifen or individualise the dose. The investigator may change the daily tamoxifen from 20 mg per day to: a halved dose to 10 mg, or a doubled dose to 40 mg. The recommendation for oral intake of tablet(s) tamoxifen for a daily dose of 10, 20 or 40 mg is accordingly: for 10 mg: one tablet (20 mg) every two days for 20 mg: one tablet (20 mg) every day for 40 mg: two tablets (20 mg) every day.

Individualised care with tamoxifen dose adjustments.

Standard adjuvant therapy of tamoxifen DRUG

The global standard dose for everyone is 20 mg orally once per day. Each subject undergoes treatment with the standard dose 20 mg daily by oral intake of one tablet, with no possibility of dose adjustment during the trial.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Karolinska Institutet: lead
• Swedish Cancer Society: collaborator
• Region Stockholm: collaborator
• The Sjöberg Foundation: collaborator
• The Cancer Research Foundations of Radiumhemmet: collaborator
• The Swedish Breast Cancer Association: collaborator

Study Sites (4)

S:a Älvsborgs Sjukhus

Borås, 501 82, Sweden

Location

Skaraborgs Sjukhus

Skövde, 549 49, Sweden

Location

Capio S:t Görans Sjukhus

Stockholm, 112 81, Sweden

Location

Södersjukhuset, Onkologiska kliniken

Stockholm, 118 61, Sweden

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Marike Gabrielson, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Jenny Bergkvist, MD, PhD

  Karolinska Institutet

  STUDY CHAIR

Central Study Contacts

Helena Aaröe, RN

CONTACT

+46852482267; powerstudien-meb@ki.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponsor representative and Chief Scientific Scientific Officer

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: March 31, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): August 1, 2036
• Study Completion (Estimated): August 1, 2036
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (4)