NCT00459771已完成3 期
Prospective, Randomized, Pharmacological Intervention Study; Evaluating Effect of the Angiotensin II-receptor (AT1) Blocker Candesartan vs Placebo in Prevention of Trastuzumab-associated Cardiotoxicity in Patients Treated With Trastuzumab
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 210
- 试验地点
- 19
- 主要终点
- The occurrence of cardiotoxicity, defined as a decline in LVEF (MUGA) of more than 15% or a decrease of less than 15% to an absolute value below 45%.
研究概览
简要总结
Evaluating the effect of the angiotensin II-receptor (AT1) blocker candesartan vs placebo in prevention of trastuzumab-associated cardiotoxicity in patients with primary breast cancer treated with trastuzumab.
详细描述
Prospective, randomized pharmacological intervention study
Primary objectives:
- to determine whether concurrent ATII-antagonist treatment can prevent trastuzumab-related cardiotoxicity, defined as a decline in LVEF of more than 15% or a decrease to an absolute value <45%
Secondary objectives:
- To determine if 'Brain Natriuretic Peptide' (NT-proBNP) and troponin T can be used as surrogate marker in the monitoring of trastuzumab-associated cardiotoxicity
- To determine genetic variability in relevant genes such as the HER2 gene (by assessing single nucleotide polymorphisms [SNPs] in the kinase domain) and explore any correlations with trastuzumab induced cardiotoxicity 3) To determine the reversibility of a decrease in left ventricular ejection fraction (LVEF) associated with trastuzumab 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged ≥18 years
- •Strongly HER2-positive breast cancer, defined as an immunohistochemistry score of 3+ using the HercepTestTM, or gene amplification by fluorescence in situ hybridization, or chromogenic in situ hybridization (CISH).
- •Serum creatinine <140 umol/l or creatinine clearance > 50 ml/min (by Cockcroft-Gault formula)
- •Thyroid stimulating hormone between 0.5-3.9 MU/l
- •Blood pressure systolic ≥ 140 mmHg and diastolic ≥ 90 mmHg is acceptable at randomization. However prior to the first administration of trastuzumab blood pressure should be regulated and should be systolic ≥ 100 mmHg and ≤ 180 mmHg and diastolic ≥ 60 mmHg and ≤ 100 mmHg. (blood pressure should be regulated according to the guidelines of appendix 5)
- •LVEF ³ 50% assessed by multigated angiography (MUGA) or cardiac ultrasound
- •Adjuvant regimen: trastuzumab start ≥ 3 weeks after day 1 of the last anthracycline chemotherapy cycle
- •Trastuzumab treatment according to standard medical care
- •Written informed consent to participate in the study
排除标准
- •Prior anthracycline chemotherapy regimen or anti-HER2 therapy, or other prior biologic or immunotherapy for breast cancer treatment or any malignancy
- •Previous malignancy requiring chemotherapy or radiotherapy
- •Uncontrolled serious concurrent illness
- •Patients with New York Heart Association (NYHA) class II/III/IV congestive heart failure
- •Myocardial infarction < 6 months before randomization
- •Treatment with ACE inhibitor, ATII blocker, or lithium. Patients treated with ACE inhibitor, or ATII blocker can switch (after randomization and during the chemotherapy period) to alternative antihypertensive therapy; see appendix
- •History of hypersensitivity to the study medication
- •Pregnancy or breast feeding
研究组 & 干预措施
Candesartan
Active Comparator
Candasartan
干预措施: AT1 blocker candesartan (Drug)
Placebo
Placebo Comparator
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
The occurrence of cardiotoxicity, defined as a decline in LVEF (MUGA) of more than 15% or a decrease of less than 15% to an absolute value below 45%.
时间窗: during 1 year trastuzumab therapy and during 26 weeks after discontinuation of trastuzumab
次要结局
未报告次要终点
研究者
研究点 (19)
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