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

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

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Cardiotoxicity; Malignancy; Oesophagus Cancer; Fluorouracil Adverse Reaction
• Intervention / Treatment: 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)

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 Type: Observational
• Enrollment (Estimated): 75

Contacts and Locations

• Study Contact: Name: Aderonke Abiodun, MBChB; Phone Number: 02073777000; Email: aderonketemilade.abiodun@nhs.net

Study Locations

• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • Recruiting
    • St Bartholomews Hospital
    • Contact: Aderonke Abiodun, MBChB; Email: aderonketemilade.abiodun@nhs.net
    • Principal Investigator: Charlotte Manisty, PhD
    • Principal Investigator: Malcolm Walker, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with gastrointestinal malignancies being treated with a fluoropyrimidine based chemotherapy regimen.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in left ventricular ejection fraction from baseline	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months
Change in left ventricular extracellular volume from baseline	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months
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
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
Change in high sensitivity troponin T	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months
Change in sublingual perfused boundary region	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months
Change in sublingual capillary density	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months
Change in retinal vessel density	Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment	6 months

Collaborators and Investigators

• Sponsor: University College, London
• Investigators: Principal Investigator: Charlotte Manisty, PhD, UCL

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2022
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): February 1, 2024

Study Registration Dates

• First Submitted: April 27, 2022
• First Submitted That Met QC Criteria: September 15, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 15, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Cardiotoxicity; Cardio-oncology; Fluoropyrimidine cardiotoxicity
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Pathologic Processes; Heart Diseases; Neoplasms; Neoplasms by Site; Wounds and Injuries; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Cardiovascular Diseases; Esophageal Neoplasms; Cardiotoxicity
• Other Study ID Numbers: 142669

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No