Clinical trial NCT06605833: A Feasibility Study to Investigate LATe CaRdiac ToxicIty Following ImmUnotherapy Treatment for Melanoma
Official title: ATRIUM - a Feasibility Study to Investigate LATe CaRdiac ToxIcity Following ImmUnotherapy Treatment for Melanoma
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Melanoma Stage III or IV
Keywords: melanoma
cardiac toxicity
immune related adverse events
immunotherapy treatment
Lead sponsor: Royal Marsden NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Royal Brompton and Harefield NHS Foundation Trust
name: Royal Free Hospital NHS Foundation Trust
First posted: 2024-09-20
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Royal Marsden (RMH) and Royal Free NHS Trusts (RFH)

Brief 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). 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.

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 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.

Eligibility 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.

Primary outcomes:
measure: Acceptance rate
timeFrame: 12 months
Secondary outcomes:
measure: Adherence rate
timeFrame: 12 months
measure: Recruitment rate
timeFrame: 12 months
measure: Reasons for non-adherence or declining to consent
timeFrame: 12 months
measure: Difference in acceptance rates
timeFrame: 12 months
measure: Proportion of patients who experience cardiovascular irAEs
timeFrame: 12 months
measure: Prevalence of cardiac irAEs
timeFrame: 12 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
References: