Melanoma Stage III or IVCARD-IONCT06605833
CARDiac Toxicity Following ImmunOtherapy Treatment for Melanoma
An observational study of Melanoma Stage III or IV, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma Stage III or IV
- What is being tested?
- 12-Lead ECG, Transthoracic Echocardiogram and Cardiac MRI
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 26 Sep 2025to 30 Sep 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients from The Royal Marsden NHS Foundation Trust (RMH) and the Royal Free London NHS Trust (RFH) who are in follow up after receiving immunotherapy for melanoma 2-10+ years prior to enrolment.
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site
The Royal Marsden NHS Foundation Trust
London, SW6 3JJ
About this study
Official title: CARD-IO - CARDiac Toxicity Following ImmunOtherapy Treatment for Melanoma
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.
Read more
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.
Read the 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.
- Conditions
- Melanoma Stage III or IV
- Being tested
- 12-Lead ECG, Transthoracic Echocardiogram, Cardiac MRI, Cardiac Biomarker Screening, Basic Observations
- Keywords
- melanoma, cardiac toxicity, immune related adverse events, immunotherapy treatment
- Medical subject headings
- Melanoma, Cardiotoxicity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
12-Lead ECGDiagnostic test
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
Transthoracic EchocardiogramDiagnostic test
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
Cardiac MRIDiagnostic test
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
Cardiac Biomarker ScreeningDiagnostic test
- Cardiac Troponin I,
- NTproBNP],
- lipid profile,
- HbA1c
- ferritin
These are Standard of Care tests being performed at a non Standard of Care timepoint
Basic ObservationsOther
- Heart rate
- Blood pressure
- Oxygen SAT
- Respiratory rate
These are Standard of Care observations being performed at a non Standard of Care timepoint
| Study group | Role | What they receive |
|---|---|---|
| 2-4 years | Patients on routine follow-up 2-4 years after the completion of immunotherapy treatment for melanoma Receives: Diagnostic Test: 12-Lead ECG; Diagnostic Test: Transthoracic Echocardiogram; Diagnostic Test: Cardiac MRI; Diagnostic Test: Cardiac Biomarker Screening; Other: Basic Observations | |
| 5-7 | Patients on routine follow-up 5-7 years after the completion of immunotherapy treatment for melanoma Receives: Diagnostic Test: 12-Lead ECG; Diagnostic Test: Transthoracic Echocardiogram; Diagnostic Test: Cardiac MRI; Diagnostic Test: Cardiac Biomarker Screening; Other: Basic Observations | |
| 8-10+ | Patients on routine follow-up 8-10+ years after the completion of immunotherapy treatment for melanoma Receives: Diagnostic Test: 12-Lead ECG; Diagnostic Test: Transthoracic Echocardiogram; Diagnostic Test: Cardiac MRI; Diagnostic Test: Cardiac Biomarker Screening; Other: Basic Observations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acceptance rate
total number of patients consented divided by the number of patients invited for the study
Measured: 12 months
Secondary outcomes (6)
Adherence rate
proportion of patients completing all the scheduled cardiac screening tests divided by the number of patients enrolled in the study
Measured: 12 months
Recruitment rate
Number of patients recruited on average per month in each site, and overall
Measured: 12 months
Reasons for non-adherence or declining to consent
Reasons for non-adherence or declining to consent
Measured: 12 months
Difference in adherence rates
Difference in adherence rates between adjuvant early disease setting and metastatic setting
Measured: 12 months
Proportion of patients who experience cardiovascular irAEs
Proportion of patients who experience cardiovascular irAEs during long-term follow-up, post-treatment
Measured: 12 months
Prevalence of cardiac irAEs
Prevalence of cardiac irAEs
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2024
- Study start26 Sep 2025
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma Stage III or IVStudies of the same condition, open and under way.
- More trials run by Royal Marsden NHS Foundation TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Royal Free Hospital NHS Foundation Trust, Royal Brompton & Harefield NHS Foundation Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06605833
- Sponsor's protocol ID
- CCR6063
- Acronym
- CARD-IO
- Status last verified
- Sep 2025
- First submitted
- 18 Sep 2024
- Last updated
- 1 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: This is a feasibility study to support the application of a larger more complex study by the same team on the same topic. Sharing of IPD would require additional consents and level of complexity in the Data Plan which current resource restraints does not allow. This will be considered for future studies based on this research.
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CARD-IO - CARDiac Toxicity Following ImmunOtherapy Treatment for Melanoma
- ClinicalTrials.gov ID
- NCT06605833
- Acronym / sponsor ID
- CARD-IO / CCR6063
- Conditions
- Melanoma Stage III or IV
- Keywords
- melanoma, cardiac toxicity, immune related adverse events, immunotherapy treatment
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Royal Free Hospital NHS Foundation Trust, Royal Brompton & Harefield NHS Foundation Trust
- Study start
- 26 Sep 2025 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 20 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 2-4 years | – | Diagnostic Test: 12-Lead ECG, Diagnostic Test: Transthoracic Echocardiogram, Diagnostic Test: Cardiac MRI, Diagnostic Test: Cardiac Biomarker Screening, Other: Basic ObservationsPatients on routine follow-up 2-4 years after the completion of immunotherapy treatment for melanoma |
| 5-7 | – | Diagnostic Test: 12-Lead ECG, Diagnostic Test: Transthoracic Echocardiogram, Diagnostic Test: Cardiac MRI, Diagnostic Test: Cardiac Biomarker Screening, Other: Basic ObservationsPatients on routine follow-up 5-7 years after the completion of immunotherapy treatment for melanoma |
| 8-10+ | – | Diagnostic Test: 12-Lead ECG, Diagnostic Test: Transthoracic Echocardiogram, Diagnostic Test: Cardiac MRI, Diagnostic Test: Cardiac Biomarker Screening, Other: Basic ObservationsPatients on routine follow-up 8-10+ years after the completion of immunotherapy treatment for melanoma |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients from The Royal Marsden NHS Foundation Trust (RMH) and the Royal Free London NHS Trust (RFH) who are in follow up after receiving immunotherapy for melanoma 2-10+ years prior to enrolment.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 12-Lead ECGParticipants 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 | 2-4 years, 5-7, 8-10+ |
| Transthoracic EchocardiogramA 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 | 2-4 years, 5-7, 8-10+ |
| Cardiac MRIA 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 | 2-4 years, 5-7, 8-10+ |
| 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 | Diagnostic test | 2-4 years, 5-7, 8-10+ |
| 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 | Other | 2-4 years, 5-7, 8-10+ |
Primary outcome
Acceptance rate
Time frame: 12 months
total number of patients consented divided by the number of patients invited for the study
6 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2025.
- Individual participant dataSharing planned: No. This is a feasibility study to support the application of a larger more complex study by the same team on the same topic. Sharing of IPD would require additional consents and level of complexity in the Data Plan which current resource restraints does not allow. This will be considered for future studies based on this research.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Melanoma Stage III or IV, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 1 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acceptance rate (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2025.