Clinical trial NCT06048458: Cancer Treatment Related Cardiovascular Toxicity: Comprehensive Myocardial and Vascular Phenotyping
Official title: Cancer Treatment Related Cardiovascular Toxicity: Comprehensive Myocardial and Vascular Phenotyping
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cardiovascular Diseases
Cardiotoxicity
Fluorouracil Adverse Reaction
Malignancy
Colorectal Cancer
Oesophagus Cancer
Gastric Cancer
Pancreatic Cancer
Keywords: Cardio-oncology
Cardiotoxicity
Fluoropyrimidine cardiotoxicity
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2023-09-21
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with gastrointestinal malignancies being treated with a fluoropyrimidine based chemotherapy regimen.

Brief summary: Observational prospective cohort study designed to assess the mechanisms of fluoropyrimidine induced cardiovascular toxicity.

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.

Eligibility criteria: Inclusion Criteria:

* Age \>18 years
* Gastrointestinal malignancy
* Receiving fluoropyrimidine chemotherapy

Exclusion Criteria:

* Participants unable or unwilling to provide consent
* 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
* 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.
* Participants with significant renal impairment (eGFR\<30ml/min)
* History of allergy to adenosine, gadolinium or iodinated contrast
* Patients with terminal illness (life expectancy \<6 months) will be excluded.

Primary outcomes:
measure: Change in myocardial blood flow from baseline with adenosine stress assessed by quantitative perfusion cardiac MRI
timeFrame: 6 months
Secondary outcomes:
measure: Change in left ventricular ejection fraction from baseline
timeFrame: 6 months
measure: Change in left ventricular extracellular volume from baseline
timeFrame: 6 months
measure: Change in left ventricular global longitudinal strain from baseline
timeFrame: 6 months
measure: Change in N-terminal pro B-type natriuretic peptide (NT-pro BNP)
timeFrame: 6 months
measure: Change in high sensitivity troponin T
timeFrame: 6 months
measure: Change in sublingual perfused boundary region
timeFrame: 6 months
measure: Change in sublingual capillary density
timeFrame: 6 months
measure: Change in retinal vessel density
timeFrame: 6 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: St Bartholomews Hospital
Study officials:
affiliation: UCL
name: Charlotte Manisty, PhD
role: PRINCIPAL_INVESTIGATOR
References: