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

Официальное название

The POWER Trial: A Randomised, Two-armed Open Label Phase 3 Clinical Trial on Personalised Dose Optimisation With Adjuvant Tamoxifen Therapy After Breast Cancer to Investigate the Impact on Discontinuation and Efficacy Compared to Standard of Care

Обзор

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.

Вмешательства

• Препарат Individual dose of tamoxifen
  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: fo
• Препарат Standard adjuvant therapy of tamoxifen
  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.

Первичные конечные точки

• Discontinuation of tamoxifen. [Срок оценки: From enrollment to end of treatment at 60 months.]

Вторичные конечные точки (11)

• Patient reported outcomes. [Срок оценки: From enrollment to end of treatment at 60 months.]
• Quality of life questionnaire [Срок оценки: From enrollment to end of treatment at 60 months.]
• Concentration of circulation plasma metabolites [Срок оценки: From 3 months after treatment start to end of treatment at 60 months]
• Invasive disease-free survival (iDSF) [Срок оценки: From enrollment to end of treatment at 60 months.]
• Distant relapse-free survival (DRFS) [Срок оценки: From enrollment to end of treatment at 60 months.]
• Breast cancer specific survival (BCSS) [Срок оценки: From enrollment to end of treatment at 60 months.]
• Overall survival (OS) [Срок оценки: From enrollment to end of treatment at 60 months.]
• Mammographic breast density [Срок оценки: From enrollment to end of treatment at 60 months.]
• Cost effectiveness Analysis (CEA) [Срок оценки: From enrollment to end of treatment at 60 months.]
• Cost-Benefit Analysis (CBA) [Срок оценки: From enrollment to end of treatment at 60 months.]
• Incremental cost-effectiveness ratio (ICER) [Срок оценки: From enrollment to end of treatment at 60 months.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Швеция · 4 центра

• S:a Älvsborgs Sjukhus — Borås
• Skaraborgs Sjukhus — Skövde
• Capio S:t Görans Sjukhus — Stockholm
• Södersjukhuset, Onkologiska kliniken — Stockholm

Идентификаторы

NCT: NCT07502820 · 2025-522240-40-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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