Immune Checkpoint Inhibitor Therapy for Cancer and Risk of Myocarditis or Cardiomyopathy

June 6, 2024 updated by: Dr. Christian Houbois, Sunnybrook Health Sciences Centre

Association of Immune Checkpoint Inhibitor Therapy for Cancer With Early Myocardial Tissue and Biomarker Changes During Treatment - Implication for Risk of Myocarditis and Cardiomyopathy

Patients undergoing dual treatment with Immune checkpoint inhibitors (ICI) for various cancers, e.g. melanoma, are at increased risk of developing myocarditis and cardiomyopathy. Currently, only limited data on serial myocardial tissue changes during treatment and whether they predict outcomes are available. Cardiac MRI (CMR) is the reference standard for non-invasive myocardial volumes/function analysis and uniquely characterizes myocardial tissue. Therefore, it may help detect myocardial tissue changes during treatment and help early treatment and prevent adverse cardiac outcomes.

Study Overview

Status

Recruiting

Conditions

Detailed Description

As patients going through cancer therapy live longer, they are at a higher risk of developing cardiovascular disease. Hence the evolving field of Cardio-Oncology has garnered much attention and importance. In recent years, immune checkpoint inhibitors (ICI) have become an essential component of cancer therapy, significantly improving patient outcomes that were previously considered palliative, e.g. metastatic melanoma, renal cell or lung cancer, and these therapies have improved survival.

With ICI therapy and especially with combination therapy, patients may develop severe ICI-related adverse events, e.g. myocarditis (1-5%) which is fatal in 30-50% of the patients. Another more significant subgroup of patients will develop non-inflammatory cardiomyopathy or other major cardiac events like cardiovascular death, cardiac arrest etc. There is also evidence that during ICI treatment atherosclerotic disease may progress. Identifying patients at risk for both remains a major challenge and is a knowledge gap in Cardio-Oncology.

Cardiovascular magnetic resonance (CMR) is a unique, highly reproducible, multiparametric method for non-invasive myocardial tissue characterization for diagnosing myocardial inflammation. Biomarkers like quantitative cardiac relaxometry (T1/T2-Mapping) with extracellular volume fraction (ECV), delayed gadolinium enhancement (LGE) or myocardial strain show insights into myocardial tissue composition. These biomarkers have the potential to identify early myocardial changes before the risk of clinical myocarditis or non-inflammatory cardiomyopathy occurs and may therefore help identify early myocardial tissue changes during ICI treatment and help identify patients at risk early on. Also, CMR can assess the aorta with high temporal and spatial resolution to identify atherosclerotic changes.

Only a few retrospective studies and case reports with small numbers of patients have investigated ICI-related cardiac events during treatment. Evidence shows that many patients present with heart failure (~80%), but troponin is only elevated in ~45%. This indicates that ICI-associated left ventricular (LV) dysfunction may exist without troponin elevation. Other data suggests that the ICI-associated myocardial tissue inflammation pattern might differ from viral myocarditis. The myocardial T1/T2 relaxation times may be elevated during ICI-associated myocardial inflammation. There is also evidence that strain changes are associated with adverse events within 30 days of treatment. However, all these studies demonstrate CMR findings when patients have already developed LV dysfunction or myocarditis. The proposed project would be the first prospective study to get deeper insights into serial, systematic ICI-associated myocardial tissue changes during treatment and their correlation with serum biomarkers and clinical symptoms.

Study Type

Observational

Enrollment (Estimated)

15

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

This pilot study will include 15 patients recruited from Odette Cancer Centre at Sunnybrook Health Sciences Center who have skin cancer and are eligible for immunotherapy treatment.

Description

Inclusion Criteria:

  • All patients 18 years of age, or older, with skin cancer and eligible for ICI treatment with a combination of a) nivolumab, b) pembrolizumab, or c) ipilimumab.
  • Able to provide informed consent
  • Able to travel to SHSC for cardiac imaging.

Exclusion Criteria:

  • Life expectancy equal to, or less than, 12 months
  • Participating in another clinical trial
  • Treated with ICI in the past
  • History of cardiac disease (e.g. heart failure, myocardial infarction, atrial fibrillation, unstable angina)
  • Pregnant patients
  • Impaired renal function (GFR equal to, or less than, 30mL/min)
  • Contraindications for MRI (e.g. pacemaker).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Patients with skin cancer eligible for dual ICI treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Define changes in CMR tissue and blood biomarkers during ICI treatment.
Time Frame: Baseline, 6 weeks and 6 months

The following parameters are investigated to assess for underlying myocardial remodelling and/or inflammation during treatment with ICI.

Left ventricular volumes in ml Left ventricular ejection fraction in percentage T1 Mapping: T1 relaxation time in milliseconds T2 Mapping: T2 relaxation time in milliseconds ECV = (1-hematocrit) × (Δ(1/T1myocardium)/Δ(1/T1blood)) in percentage Strain (GCS, GLS, GRS) reported as a percentage, formula =(Max Length-Initial Length)/Initial Length LGE is qualitatively described as categorical variables e.g. epicardial, mid-myocardial, subendocardial or transmural.

LGE is quantified as mass in gram and as percentage of the LV mass. High sensitivity troponin 1 nanogram/ mL B-type natriuretic peptide (BNP) nanogram/L High sensitivity CRP in mg/L
Baseline, 6 weeks and 6 months
Investigate associations between CMR imaging biomarkers and CMR-defined left ventricular ejection fraction.
Time Frame: Baseline, 6 weeks and 6 months

This analysis is to determine if the biomarkers are associated with LVEF changes over time.

Left ventricular volumes in ml Left ventricular ejection fraction in percentage T1 Mapping: T1 relaxation time in milliseconds T2 Mapping: T2 relaxation time in milliseconds ECV = (1-hematocrit) × (Δ(1/T1myocardium)/Δ(1/T1blood)) in percentage Strain (GCS, GLS, GRS) reported as a percentage, formula =(Max Length-Initial Length)/Initial Length LGE is qualitatively described as categorical variables e.g. epicardial, mid-myocardial, subendocardial or transmural.

LGE is quantified as mass in gram and as percentage of the LV mass.
Baseline, 6 weeks and 6 months
Investigate associations between serum biomarkers and CMR-defined left ventricular ejection fraction.
Time Frame: Baseline, 6 weeks and 6 months

This analysis is to determine if blood biomarkers are associated with LVEF changes over time.

High sensitivity troponin 1 nanogram/ mL B-type natriuretic peptide (BNP) nanogram/L High sensitivity CRP in mg/L
Baseline, 6 weeks and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sunnybrook Health Sciences Centre

Investigators

  • Principal Investigator: Christian Houbois, MD, Sunnybrook Health Sciences Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2024

Primary Completion (Estimated)

September 30, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

February 12, 2024

First Submitted That Met QC Criteria

March 7, 2024

First Posted (Actual)

March 13, 2024

Study Record Updates

Last Update Posted (Actual)

June 7, 2024

Last Update Submitted That Met QC Criteria

June 6, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5993

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No plan to share individual participant data with other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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