Cancer Treatment Related Cardiovascular Toxicity: Comprehensive Myocardial and Vascular Phenotyping

Recruiting

• Conditions: Oesophagus Cancer; Cardiovascular Diseases; Fluorouracil Adverse Reaction; Cardiotoxicity; Colorectal Cancer; Gastric Cancer; Pancreatic Cancer; Malignancy
• Interventions: Diagnostic Test: Cardiovascular magnetic resonance with stress perfusion; Diagnostic Test: CT coronary angiography; Diagnostic Test: Retinal OCT angiography; Diagnostic Test: Sublingual microscopy (GlycoCheck); Diagnostic Test: Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP)

• Registration Number: NCT06048458
• Lead Sponsor: University College, London

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.

Study Timeline

• Study First Submitted: 2022-04-27
• Study Start: 2022-05-18
• Status Verified: 2022-12
• Study First Submitted QC: 2023-09-15
• Last Update Submitted: 2023-09-15
• Study First Posted: 2023-09-21
• Last Update Posted: 2023-09-21
• Primary Completion: 2023-12
• Study Completion: 2024-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 75

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort 1	Retinal OCT angiography	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.
Cohort 2	Cardiovascular magnetic resonance with stress perfusion	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.
Cohort 2	Sublingual microscopy (GlycoCheck)	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.
Cohort 2	Retinal OCT angiography	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.
Cohort 1	CT coronary angiography	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.
Cohort 1	Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP)	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.
Cohort 1	Cardiovascular magnetic resonance with stress perfusion	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.
Cohort 1	Sublingual microscopy (GlycoCheck)	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.
Cohort 2	CT coronary angiography	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.
Cohort 2	Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP)	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 sublingual perfused boundary region	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 sublingual capillary density	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 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 retinal vessel density	6 months	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
Change in left ventricular ejection fraction from baseline	6 months	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment

Trial Locations

Locations (1)

St Bartholomews Hospital; 🇬🇧 London, United Kingdom