A Feasibility Study to Investigate LATe CaRdiac ToxicIty Following ImmUnotherapy Treatment for Melanoma

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A Feasibility Study to Investigate LATe CaRdiac ToxicIty Following ImmUnotherapy Treatment for Melanoma

Study Purpose

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 your 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 ATRIUM 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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Written informed consent.

- Age 18 years or older.

- Confirmed diagnosis of melanoma.

- Stage II high risk 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.

- 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06605833
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Royal Marsden NHS Foundation Trust
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries	United Kingdom
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Melanoma Stage III or IV

Additional Details

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 acceptance 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 questionnaires 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 and their GPs, and abnormal results will be investigated as per standard of care. The prevalence of cardiac adverse events will be summarised.

Arms & Interventions

Arms

: 2- 10+ years

Patients on routine follow-up, at 2 to 10+ (inclusive) following the completion of immunotherapy treatment for melanoma. These will be looked at in groups of 2 - 4 years, 5 - 7 years and 8 - 10+ years.

Interventions

Diagnostic Test: - 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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.