Investigating Cardiovascular Adverse Events Related to Cancer Treatment: a Study of Extreme Toxicity Using Induced Pluripotent Stem Cells
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Comparison between iPSC-derived cells
研究概览
简要总结
Cisplatin, anthracyclines, bleomycin and trastuzumab can cause severe cardiovascular or pulmonary toxicity. Why some patients are susceptible to extreme toxicity of cancer treatment is largely unknown. Unraveling extreme cardiovascular toxic responses in cancer patients may help understand the pathophysiology of cardiovascular toxicity of these agents and help in understanding the more subtle, long-term cardiovascular side effects that affect a larger part of cancer survivors. With induced pluripotent stem cells we will obtain patient-derived cells to recapitulate and mimic and study pathological (cardiovascular) responses and (cardiovascular) toxicity in vitro.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In order to be eligible to participate in this study, a subject must meet all of these criteria:
- •any proven cancer treated with curative intent;
- •age ≥ 18 and ≤ 50 years;
- •able to comply with the protocol;
- •signed written informed consent.
- •There are specific inclusion criteria for every subject group:
- •severe toxicity during 1 to 3 cycles of anthracyclines;
- •≥ 3 months after end of cancer treatment which included the maximum tolerable dose of anthracyclines without (severe) toxicity;
- •severe toxicity within 1 to 6 cycles of trastuzumab;
- •≥ 3 months after end of cancer treatment which included a year of trastuzumab without (severe) toxicity.
- •severe toxicity during 1 to 3 cycles of cisplatin;
- •≥ 1 year after end of cancer treatment which included high-dose cisplatin without toxicity;
- •severe toxicity during 1 to 3 cycles of bleomycin;
- •≥ 1 year after end of cancer treatment which included high-dose bleomycin without toxicity.
- •Severe toxicity is defined as any of grade 3 - 4 toxicity according to CTCAE 4.
- •A potential subject who meets any of the following exclusion criteria will be excluded from participation in this study:
- •history of cardiovascular disease prior to start of cancer treatment, as evidenced by any of the following: symptomatic or treated cardiovascular disease prior to start of cancer treatment; LVEF < 55% at any performed MUGA scan or echocardiography prior to start of cancer treatment;
- •any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol, or insufficient understanding of the Dutch language;
- •any contraindication for skin biopsy, including: extensive skin disorder precluding biopsy of unaffected skin; known allergy to local anaesthetics; use of anticoagulants and INR > 3;
- •pregnant or lactating female.
- •Furthermore, there are specific exclusion criteria for the control groups:
- •history of cardiovascular disease during or after cancer treatment, as evidenced by any of the following: any symptomatic or treated cardiovascular disease; LVEF < 55% at any performed MUGA scan or echocardiography.
排除标准
- 未提供
研究组 & 干预措施
Anthracylines-treated with toxicity
Patients with toxicity during/after treatment with anthracylines.
干预措施: Anthracyclines (Drug)
Anthracyclines-treated without toxicity
Patients without toxicity during/after treatment with anthracylines.
干预措施: Anthracyclines (Drug)
Trastuzumab-treated with toxicity
Patients with toxicity during/after treatment with trastuzumab.
干预措施: Trastuzumab (Drug)
Trastuzumab-treated without toxicity
Patients without toxicity during/after treatment with trastuzumab.
干预措施: Trastuzumab (Drug)
Cisplatin-treated with toxicity
Patients with toxicity during/after treatment with cisplatin.
干预措施: Cisplatin (Drug)
Cisplatin-treated without toxicity
Patients without toxicity during/after treatment with cisplatin.
干预措施: Cisplatin (Drug)
Bleomycin-treated with toxicity
Patients with toxicity during/after treatment with bleomycin.
干预措施: Bleomycin (Drug)
Bleomycin-treated without toxicity
Patients without toxicity during/after treatment with bleomycin.
干预措施: Bleomycin (Drug)
结局指标
主要结局
Comparison between iPSC-derived cells
时间窗: 3 years
Comparison between iPSC-derived cells from toxicity cases and controls, for each of the four different agents.
次要结局
- Correlate the findings from the iPSC-derived cells with the clinical phenotype of cardiovascular toxicity(3 years)