Investigating Cardiovascular Adverse Events Related to Cancer Treatment

NCT03199300 | Active Not Recruiting

• 1 other identifier: 201700454
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiovascular Morbidity; Cancer, Treatment-Related; Toxicity Due to Chemotherapy

Keywords

bleomycin; cisplatin; trastuzumab; anthracyclines; toxicity

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Correlate the findings from the iPSC-derived cells with the clinical phenotype of cardiovascular toxicity

  3 years

Study Arms (8)

Anthracylines-treated with toxicity

Patients with toxicity during/after treatment with anthracylines.

Drug: Anthracyclines

Anthracyclines-treated without toxicity

Patients without toxicity during/after treatment with anthracylines.

Drug: Anthracyclines

Trastuzumab-treated with toxicity

Patients with toxicity during/after treatment with trastuzumab.

Drug: Trastuzumab

Trastuzumab-treated without toxicity

Patients without toxicity during/after treatment with trastuzumab.

Drug: Trastuzumab

Cisplatin-treated with toxicity

Patients with toxicity during/after treatment with cisplatin.

Drug: Cisplatin

Cisplatin-treated without toxicity

Patients without toxicity during/after treatment with cisplatin.

Drug: Cisplatin

Bleomycin-treated with toxicity

Patients with toxicity during/after treatment with bleomycin.

Drug: Bleomycin

Bleomycin-treated without toxicity

Patients without toxicity during/after treatment with bleomycin.

Drug: Bleomycin

Interventions

Anthracyclines DRUG

Chemotherapy regimen containing anthracyclines.

Anthracyclines-treated without toxicity; Anthracylines-treated with toxicity

Trastuzumab DRUG

Systemic treatment including trastuzumab.

Trastuzumab-treated with toxicity; Trastuzumab-treated without toxicity

Cisplatin DRUG

Chemotherapy including cisplatin.

Cisplatin-treated with toxicity; Cisplatin-treated without toxicity

Bleomycin DRUG

Chemotherapy including bleomycin.

Bleomycin-treated with toxicity; Bleomycin-treated without toxicity

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients treated for a malignancy with any of the described cytotoxic agents.

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

Urine sample, blood sample, germline DNA, skin fibroblasts.

MeSH Terms

Conditions

Neoplasms, Second Primary

Interventions

Anthracyclines; Trastuzumab; Cisplatin; Bleomycin

Condition Hierarchy (Ancestors)

Neoplasms

Intervention Hierarchy (Ancestors)

Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Glycopeptides; Glycoconjugates; Peptides

Study Officials

• J.A. Gietema, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2017
• First Posted: June 26, 2017
• Study Start: December 12, 2017
• Primary Completion: February 6, 2025
• Study Completion (Estimated): January 1, 2027
• Last Updated: December 11, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)