Cancer Treatment Related Cardiovascular Toxicity: Comprehensive Myocardial and Vascular Phenotyping

Colorectal Cancer Clinical Trial

— PC-TOX  

Official title:

Cancer Treatment Related Cardiovascular Toxicity: Comprehensive Myocardial and Vascular Phenotyping

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06048458
• Other study ID #: 142669
• Status: Recruiting
• Start date: May 18, 2022
• Est. completion date: February 2024

Study information

• Verified date: December 2022
• Source: University College, London
• Contact: Aderonke Abiodun, MBChB
• Phone: 02073777000
• Email: aderonketemilade.abiodun[@]nhs.net
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: February 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiotoxicity
• Cardiovascular Diseases
• Colorectal Cancer
• Esophageal Neoplasms
• Gastric Cancer
• Malignancy
• Oesophagus Cancer
• Pancreatic Cancer

Intervention

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.
• CT coronary angiography
CT coronary angiogram at baseline only in both cohorts to assess for coronary artery disease
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United Kingdom	St Bartholomews Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
University College, London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in myocardial blood flow from baseline with adenosine stress assessed by quantitative perfusion cardiac MRI	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months
Secondary	Change in left ventricular ejection fraction from baseline	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months
Secondary	Change in left ventricular extracellular volume from baseline	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months
Secondary	Change in left ventricular global longitudinal strain from baseline	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months
Secondary	Change in N-terminal pro B-type natriuretic peptide (NT-pro BNP)	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months
Secondary	Change in high sensitivity troponin T	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months
Secondary	Change in sublingual perfused boundary region	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months
Secondary	Change in sublingual capillary density	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months
Secondary	Change in retinal vessel density	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months