CARDiac Toxicity Following ImmunOtherapy Treatment for Melanoma

Official title

CARD-IO - CARDiac Toxicity Following ImmunOtherapy Treatment for Melanoma

Overview

People who develop a type of skin cancer known as 'melanoma' are often treated with immunotherapy. The type of immunotherapy used for patients with melanoma is known as Immune Checkpoint Inhibitors (ICI). While ICI is very successful, it can lead to negative side effects that are known as 'immune related adverse events' (irAEs). These irAEs can affect any part of the body and can range in severity from mild symptoms to death. There has been a lot of research on irAEs that occur during ICI, but less is known about how irAEs can affect people in the long-term. Although irAEs are common from ICI, acute irAEs affecting the heart (cardiac irAEs) are uncommon. However, as they relate to the heart, they are often serious and have a higher rate of death compared to other types of irAEs. Little is known regarding the long-term effects of ICI on the heart. However, there is some evidence to suggest that ICI may also cause long-term cardiac irAEs such as accelerating a build-up of fatty materials in the arteries known as 'atherosclerosis' and inflammation of plaque in the heart. This can lead to an increased risk of heart attack. Although there are guidelines for patients on ICI treatment to receive investigations to look for irAEs, including cardiac irAEs, there are no guidelines for monitoring long-term survivors. The aim of the CARD-IO study is to establish if it is possible to investigate in long-term follow-up cardiac side-effects in patients who received ICI for melanoma. The data for this study would be used to support a larger study in the same patient population. Potentially, this could lead to a change in guidelines and long-term follow-up care for melanoma patients who have received ICI.

Detailed description

Primary aim • To establish the feasibility of conducting a study to investigate late cardiac side effects caused by immunotherapy in patients with melanoma in order to generate data to support a larger study in this patient population.

Secondary aims

* To assess factors impacting on the acceptance and adherence with cardiac investigations. * To contribute to the understanding of long-term cardiac toxicities following immunotherapy which will enable their early recognition.

Primary endpoint

• Acceptance rate (reported as the total number of patients consented divided by the number of patients invited for the study).

Secondary endpoints

* Adherence rate (reported as the proportion of patients completing all the scheduled cardiac screening tests divided by the number of patients enrolled in the study). * Recruitment rate (reported as the number of patients recruited on average per month in each site, and overall). * Reasons for non-adherence or declining to consent. * Difference in adherence rates between adjuvant early disease setting and metastatic setting. * Proportion of patients who experience cardiac irAEs during long-term follow-up, post-treatment. * Prevalence of cardiac irAEs.

The planned sample size is 60 participants.

The project will assess 3 groups of patients at different timepoints during their standard of care surveillance, at 2-4, 5-7 and 8-10 years following the completion of their immunotherapy treatment for melanoma. Patients on routine follow-up, at 2 to 10 years following the completion of immunotherapy treatment for melanoma will be identified by searching through database of patients with melanoma who received immune checkpoint inhibitors (ICI). Patients respecting the inclusion criteria will be invited to take to part to the study.

Patients included in the study will undergo screening blood tests including cardiac biomarkers (troponin I, NTproBNP, lipid profile, HbA1c, ferritin), a 12 lead ECG and transthoracic echocardiography, a cardiac MRI alongside completing a questionnaire about cardiac events and risk factors. Patients will have blood tests done at Royal Marsden or Royal Free, while all the other cardiac investigations (ECG, transthoracic echocardiography, cardiac MRI) will be performed at the Royal Brompton Hospital. Surveillance imaging performed as per standard of care at the Royal Marsden or at the Royal Free will be reviewed for evidence of atherosclerosis by the team at the Royal Brompton. The cardiology team at the Royal Brompton will review cardiac investigations' results and abnormal results will be flagged.

A summary report will be generated and sent to the patients, their GPs, and the Site irrespective of the results found, and abnormal results will be investigated as per standard of care. The prevalence of cardiac adverse events will be summarised.

Interventions

• Diagnostic test 12-Lead ECG
  Participants will undergo a standard 12-lead ECG in order to record the electrical activity of the heart. This typically takes a few minutes and the ECG is read by a cardiologist This is a Standard of Care test being performed at a non Standard of Care timepoint
• Diagnostic test Transthoracic Echocardiogram
  A transthoracic echocardiogram will be performed in accordance to standard British Society of Echocardiography guidelines. This will involve undertaking an ultrasound scan of the participant's heart with ultrasound jelly to obtain information including left ventricular function and valvular function. This is a Standard of Care test being performed at a non Standard of Care timepoint
• Diagnostic test Cardiac MRI
  A cardiac MRI scan will be performed in order to assess the morphology and function of the heart in accordance with international guidelines. Data that will be derived includes biventricular volumes and function and myocardial strain data. This is a Standard of Care test being performed at a non Standard of Care timepoint
• Diagnostic test Cardiac Biomarker Screening
  * Cardiac Troponin I, * NTproBNP\], * lipid profile, * HbA1c * ferritin These are Standard of Care tests being performed at a non Standard of Care timepoint
• Other Basic Observations
  * Heart rate * Blood pressure * Oxygen SAT * Respiratory rate These are Standard of Care observations being performed at a non Standard of Care timepoint

Primary outcome measures

• Acceptance rate [Time frame: 12 months]

Secondary outcome measures (6)

• Adherence rate [Time frame: 12 months]
• Recruitment rate [Time frame: 12 months]
• Reasons for non-adherence or declining to consent [Time frame: 12 months]
• Difference in adherence rates [Time frame: 12 months]
• Proportion of patients who experience cardiovascular irAEs [Time frame: 12 months]
• Prevalence of cardiac irAEs [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Written informed consent
• Age 18 years or older
• Confirmed diagnosis of melanoma
• Stage IIB or IIC or stage III or stage IV melanoma
• Previous immunotherapy with immune-checkpoint inhibitors (anti PD-(L)1 +/- anti CTLA-4) for melanoma
• On standard of care surveillance, at 2 to 10+ years following the completion of immunotherapy treatment

Exclusion criteria

• Medical or psychological condition that would preclude informed consent.
• Known contraindications to MRI, such as claustrophobia, pregnancy, or indwelling metallic implant which is not MR conditional
• Current active treatment with systemic therapy for any malignancy.
• Active treatment with systemic therapy for any malignancy started after the completion of immunotherapy for melanoma.
• Subjects unable to comply with the study or sample schedule.
• Planned participation in a drug trial receiving investigational agents.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United Kingdom · 1 center

• The Royal Marsden NHS Foundation Trust — London

Identifiers

NCT: NCT06605833 · CCR6063

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗