Cancer Treatment Related Cardiovascular Toxicity: Comprehensive Myocardial and Vascular Phenotyping (PC-TOX)
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ClinicalTrials.gov Identifier: NCT06048458 |
Recruitment Status :
Recruiting
First Posted : September 21, 2023
Last Update Posted : September 21, 2023
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Condition or disease | Intervention/treatment |
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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) |
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 |
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 |
Group/Cohort | Intervention/treatment |
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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.
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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.
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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. |
- 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
- 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
- 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
- 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
- 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
- Change in high sensitivity troponin T [ Time Frame: 6 months ]Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
- Change in sublingual perfused boundary region [ Time Frame: 6 months ]Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
- Change in sublingual capillary density [ Time Frame: 6 months ]Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
- Change in retinal vessel density [ Time Frame: 6 months ]Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment
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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 |
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.
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
Contact: Aderonke Abiodun, MBChB | 02073777000 | aderonketemilade.abiodun@nhs.net |
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 |
Principal Investigator: | Charlotte Manisty, PhD | UCL |
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 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Cardio-oncology Cardiotoxicity Fluoropyrimidine cardiotoxicity |
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 |