Toxicity Due to Chemotherapy, Cardiovascular Morbidity, Cancer, Treatment-Related
Conditions
Keywords
bleomycin, cisplatin, trastuzumab, anthracyclines, toxicity
Brief summary
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.
Interventions
DRUGAnthracyclines
Chemotherapy regimen containing anthracyclines.
DRUGTrastuzumab
Systemic treatment including trastuzumab.
DRUGCisplatin
Chemotherapy including cisplatin.
DRUGBleomycin
Chemotherapy including bleomycin.
Sponsors
University Medical Center Groningen
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of these criteria: 1. any proven cancer treated with curative intent; 2. age ≥ 18 and ≤ 50 years; 3. able to comply with the protocol; 4. 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 4.03. A potential subject who meets any of the following
Exclusion criteria
will be excluded from participation in this study: 1. 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; 2. any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol, or insufficient understanding of the Dutch language; 3. 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; 4. pregnant or lactating female. Furthermore, there are specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison between iPSC-derived cells | 3 years | Comparison between iPSC-derived cells from toxicity cases and controls, for each of the four different agents. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlate the findings from the iPSC-derived cells with the clinical phenotype of cardiovascular toxicity | 3 years | Correlate the findings from the iPSC-derived cells with the clinical phenotype of (cardiovascular) toxicity, assessed by circulating biomarkers and cardiac or vascular imaging. |
Countries
Netherlands
Outcome results
None listed