PC-TOX: Cancer Treatment Related Cardiovascular Toxicity: Comprehensive Myocardial and Vascular Phenotyping
Study Details
Study Description
Brief Summary
Observational prospective cohort study designed to assess the mechanisms of fluoropyrimidine induced cardiovascular toxicity.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
Fluoropyrimidine (5-FU and Capecitabine) based chemotherapy regimens form the cornerstone of treatments for gastrointestinal (GI) cancers. Fluoropyrimidines however, are associated with the development of cardiovascular toxicity which can take on different forms including chest pain, myocardial infarction, arrhythmias, heart failure and sudden death. The underlying mechanisms of cardiovascular toxicity are not fully understood.
The investigators will use quantitative cardiovascular magnetic resonance perfusion imaging, CT coronary angiography, extra-cardiac vascular assessments and serum cardiac biomarkers to improve insights into the pathophysiology of fluoropyrimidine cardiotoxicity. All enrolled participants in this two centre study will have GI cancers requiring treatment with fluoropyrimidine chemotherapy.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Cohort 1 Stable patients with gastrointestinal malignancies will be recruited to this 3 timepoint study prior to initiation of fluoropyrimidine chemotherapy. All investigations will be performed at baseline, at the end of cycle 1 and 4-6 weeks post completion of treatment. |
Diagnostic Test: Cardiovascular magnetic resonance with stress perfusion
Cardiac MRI scan to assess changes in left ventricular function, parametric mapping, strain and myocardial blood flow. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.
Diagnostic Test: CT coronary angiography
CT coronary angiogram at baseline only in both cohorts to assess for coronary artery disease
Diagnostic Test: Retinal OCT angiography
Retinal OCTa to assess changes in retinal vasculature. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.
Diagnostic Test: Sublingual microscopy (GlycoCheck)
To determine changes in sublingual microvascular health. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.
Diagnostic Test: Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP)
Performed to assess for myocardial injury. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.
|
| Cohort 2 Patients with gastrointestinal malignancies presenting to hospital with acute symptoms of fluoropyrimidine cardiotoxicity. All investigations will be performed during the acute presentation and the second visit will be performed 4-6 weeks post completion of treatment. |
Diagnostic Test: Cardiovascular magnetic resonance with stress perfusion
Cardiac MRI scan to assess changes in left ventricular function, parametric mapping, strain and myocardial blood flow. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.
Diagnostic Test: CT coronary angiography
CT coronary angiogram at baseline only in both cohorts to assess for coronary artery disease
Diagnostic Test: Retinal OCT angiography
Retinal OCTa to assess changes in retinal vasculature. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.
Diagnostic Test: Sublingual microscopy (GlycoCheck)
To determine changes in sublingual microvascular health. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.
Diagnostic Test: Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP)
Performed to assess for myocardial injury. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.
|
Outcome Measures
Primary Outcome Measures
- Change in myocardial blood flow from baseline with adenosine stress assessed by quantitative perfusion cardiac MRI [6 months]
Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
Secondary Outcome Measures
- Change in left ventricular ejection fraction from baseline [6 months]
Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
- Change in left ventricular extracellular volume from baseline [6 months]
Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
- Change in left ventricular global longitudinal strain from baseline [6 months]
Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
- Change in N-terminal pro B-type natriuretic peptide (NT-pro BNP) [6 months]
Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
- Change in high sensitivity troponin T [6 months]
Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
- Change in sublingual perfused boundary region [6 months]
Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
- Change in sublingual capillary density [6 months]
Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
- Change in retinal vessel density [6 months]
Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age >18 years
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Gastrointestinal malignancy
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Receiving fluoropyrimidine chemotherapy
Exclusion Criteria:
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Participants unable or unwilling to provide consent
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Participants that have a conventional contraindication for magnetic resonance imaging (MRI) including permanent implantable cardiac devices, ferromagnetic implants, pregnancy, large body size not fitting into the scanner bore and severe claustrophobia will be excluded
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Participants that have a conventional contraindication for adenosine stress perfusion including a history of trifascicular block or of second-degree heart block or higher on ECG, or uncontrolled asthma.
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Participants with significant renal impairment (eGFR<30ml/min)
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History of allergy to adenosine, gadolinium or iodinated contrast
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Patients with terminal illness (life expectancy <6 months) will be excluded.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | St Bartholomews Hospital | London | United Kingdom | EC1A 7BE |
Sponsors and Collaborators
- University College, London
Investigators
- Principal Investigator: Charlotte Manisty, PhD, UCL
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 142669