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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06048458
Recruitment Status : Recruiting
First Posted : September 21, 2023
Last Update Posted : September 21, 2023
Sponsor:
Information provided by (Responsible Party):
University College, London

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

Condition or disease Intervention/treatment
Cardiovascular Diseases Cardiotoxicity Fluorouracil Adverse Reaction Malignancy Colorectal Cancer Oesophagus Cancer Gastric Cancer Pancreatic Cancer 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 Design
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Study Type : Observational
Estimated Enrollment : 75 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cancer Treatment Related Cardiovascular Toxicity: Comprehensive Myocardial and Vascular Phenotyping
Actual Study Start Date : May 18, 2022
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine


Groups and Cohorts
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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.


Outcome Measures
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Primary Outcome Measures :
  1. Change in myocardial blood flow from baseline with adenosine stress assessed by quantitative perfusion cardiac MRI [ Time Frame: 6 months ]
    Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment


Secondary Outcome Measures :
  1. Change in left ventricular ejection fraction from baseline [ Time Frame: 6 months ]
    Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment

  2. Change in left ventricular extracellular volume from baseline [ Time Frame: 6 months ]
    Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment

  3. Change in left ventricular global longitudinal strain from baseline [ Time Frame: 6 months ]
    Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment

  4. Change in N-terminal pro B-type natriuretic peptide (NT-pro BNP) [ Time Frame: 6 months ]
    Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment

  5. Change in high sensitivity troponin T [ Time Frame: 6 months ]
    Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment

  6. Change in sublingual perfused boundary region [ Time Frame: 6 months ]
    Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment

  7. Change in sublingual capillary density [ Time Frame: 6 months ]
    Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment

  8. Change in retinal vessel density [ Time Frame: 6 months ]
    Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Adult patients with gastrointestinal malignancies being treated with a fluoropyrimidine based chemotherapy regimen.
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06048458


Contacts
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Contact: Aderonke Abiodun, MBChB 02073777000 aderonketemilade.abiodun@nhs.net

Locations
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United Kingdom
St Bartholomews Hospital Recruiting
London, United Kingdom, EC1A 7BE
Contact: Aderonke Abiodun, MBChB       aderonketemilade.abiodun@nhs.net   
Principal Investigator: Charlotte Manisty, PhD         
Principal Investigator: Malcolm Walker, MD         
Sponsors and Collaborators
University College, London
Investigators
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Principal Investigator: Charlotte Manisty, PhD UCL
More Information
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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT06048458    
Other Study ID Numbers: 142669
First Posted: September 21, 2023    Key Record Dates
Last Update Posted: September 21, 2023
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University College, London:
Cardio-oncology
Cardiotoxicity
Fluoropyrimidine cardiotoxicity
Additional relevant MeSH terms:
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Esophageal Neoplasms
Cardiovascular Diseases
Cardiotoxicity
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
 Heart Diseases
Pathologic Processes
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Radiation Injuries
Wounds and Injuries
Head and Neck Neoplasms
Esophageal Diseases