Investigating Cardiovascular Adverse Events Related to Cancer Treatment

Cardiovascular Morbidity Clinical Trial

— InvestiCAT  

Official title:

Investigating Cardiovascular Adverse Events Related to Cancer Treatment: a Study of Extreme Toxicity Using Induced Pluripotent Stem Cells

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03199300
• Other study ID #: 201700454
• Status: Recruiting
• Start date: December 12, 2017
• Est. completion date: January 2024

Study information

• Verified date: November 2023
• Source: University Medical Center Groningen
• Contact: J.A. Gietema, MD, PhD
• Phone: +31 50 3612821
• Email: j.a.gietema[@]umcg.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: January 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 exclusion criteria for the control groups:

5. 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.

Related Conditions & MeSH terms

• Cancer, Treatment-Related
• Cardiovascular Morbidity
• Neoplasms, Second Primary
• Toxicity Due to Chemotherapy

Intervention

Drug:
• Anthracyclines
Chemotherapy regimen containing anthracyclines.
• Trastuzumab
Systemic treatment including trastuzumab.
• Cisplatin
Chemotherapy including cisplatin.
• Bleomycin
Chemotherapy including bleomycin.

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison between iPSC-derived cells	Comparison between iPSC-derived cells from toxicity cases and controls, for each of the four different agents.	3 years
Secondary	Correlate the findings from the iPSC-derived cells with the clinical phenotype of cardiovascular toxicity	Correlate the findings from the iPSC-derived cells with the clinical phenotype of (cardiovascular) toxicity, assessed by circulating biomarkers and cardiac or vascular imaging.	3 years