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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,100
- 试验地点
- 4
- 主要终点
- Discontinuation of tamoxifen.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Individualised care with tamoxifen dose adjustments.
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.
干预措施: Individual dose of tamoxifen (Drug)
Standard-of-care with the standard tamoxifen dose of 20 mg orally once per day.
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.
干预措施: Standard adjuvant therapy of tamoxifen (Drug)
结局指标
主要结局
Discontinuation of tamoxifen.
时间窗: From enrollment to end of treatment at 60 months.
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.
次要结局
- 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.)
- Breast cancer specific survival (BCSS)(From enrollment to end of treatment at 60 months.)
- Overall survival (OS)(From enrollment to end of treatment at 60 months.)
- Mammographic breast density(From enrollment to end of treatment at 60 months.)
- Cost effectiveness Analysis (CEA)(From enrollment to end of treatment at 60 months.)
- Cost-Benefit Analysis (CBA)(From enrollment to end of treatment at 60 months.)
- Incremental cost-effectiveness ratio (ICER)(From enrollment to end of treatment at 60 months.)
研究者
Marike Gabrielson
Sponsor representative and Chief Scientific Scientific Officer
Karolinska Institutet