Cancer Treatment Related Cardiovascular Toxicity: Comprehensive Myocardial and Vascular Phenotyping (PC-TOX)

University College London (UCL)

Status: Enrolling

Conditions: Cardiotoxicity; Gastric Cancer; Fluorouracil Adverse Reaction; Oesophagus Cancer; Cardiovascular Diseases; Malignancy; Pancreatic Cancer; Colorectal Cancer

Treatments: Diagnostic Test: Sublingual microscopy (GlycoCheck); Diagnostic Test: CT coronary angiography; Diagnostic Test: Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP); Diagnostic Test: Cardiovascular magnetic resonance with stress perfusion; Diagnostic Test: Retinal OCT angiography

Study type: Observational

Funder types: Other

Identifiers

NCT06048458

142669

Details and patient eligibility

About

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

Full 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.

Enrollment: 75 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

75 participants in 2 patient groups

Cohort 1

Description:

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.

Treatment:

Diagnostic Test: Retinal OCT angiography

Diagnostic Test: Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP)

Diagnostic Test: CT coronary angiography

Diagnostic Test: Cardiovascular magnetic resonance with stress perfusion

Diagnostic Test: Sublingual microscopy (GlycoCheck)

Cohort 2

Description:

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.

Treatment:

Diagnostic Test: Retinal OCT angiography

Diagnostic Test: Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP)

Diagnostic Test: CT coronary angiography

Diagnostic Test: Cardiovascular magnetic resonance with stress perfusion

Diagnostic Test: Sublingual microscopy (GlycoCheck)