Troponin Surveillance for Cancer Immunotherapy

Overseen By Nicolas Palaskas, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

Must be taking: Immune checkpoint inhibitors

Disqualifiers: Cardiovascular event, Noncompliance, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

880 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the treatment Troponin Surveillance for Cancer Immunotherapy?

High-sensitivity cardiac troponin tests (hs-cTnI and hs-cTnT) can detect early heart damage, which is important for patients undergoing cancer treatments like immune checkpoint inhibitors that may affect the heart. Early detection of heart issues can lead to timely interventions, potentially improving patient outcomes. ^{1 2 3 4 5}

Is Troponin Surveillance safe for humans?

High-sensitivity cardiac troponins (hs-cTnT and hs-cTnI) are widely used to detect heart muscle injury and are considered safe for use in humans. They are standard biomarkers for assessing heart health, especially in detecting heart attacks and predicting heart-related events. ^{2 6 7 8 9}

How does troponin surveillance differ from other treatments for cancer immunotherapy?

Troponin surveillance is unique because it involves monitoring high-sensitivity cardiac troponin levels to detect early signs of heart damage, which can occur as a side effect of cancer immunotherapy. This approach focuses on preventing cardiotoxicity (heart damage) by identifying it early, unlike traditional cancer treatments that may not include such monitoring. ^{1 2 3 7 10}

What is the purpose of this trial?

To learn if monitoring blood levels of heart injury (troponin levels) in cancer participants treated with immune checkpoint inhibitors will lead to decreased heart-related side effects.

Research Team

Nicolas Palaskas, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults (18+) who are about to start cancer immunotherapy with immune checkpoint inhibitors and can consent to the study. It's not for those who are pregnant, breastfeeding, have a history of missing appointments, or any condition that might mess up the study results or increase their risk by participating.

Inclusion Criteria

Willingness to provide informed consent

I am planning to receive an immune therapy as part of my standard cancer treatment.

Exclusion Criteria

Inability to comply with planned study procedures

Pregnant or breast-feeding

Any factors that, in the Investigator's opinion, are likely to interfere with study procedures, such as history of noncompliance with scheduled appointments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive immune checkpoint inhibitors with troponin level monitoring for 12 weeks

12 weeks

Blood tests prior to each infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

40 weeks

Treatment Details

Interventions

• Troponin Surveillance

Trial Overview The STRICT trial is testing whether monitoring troponin levels in the blood—a sign of heart injury—can reduce heart-related side effects in patients receiving standard cancer immunotherapy treatments.

Participant Groups

Group I: Troponin Surveillance Experimental Treatment 1 Intervention

Participants in Group 1, will have blood tests performed prior to each immune checkpoint inhibitor infusion for 12 weeks.

Group II: Standard of Care Experimental Treatment 1 Intervention

Participants in Group 2, will have standard of care testing for any heart-related side effects of immune checkpoint inhibitors.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a study of 1113 patients with possible acute coronary syndrome, those with detectable but normal levels of cardiac troponin I (hs-cTnI) or T (hs-cTnT) had a significantly increased risk of major adverse cardiovascular events (MACE) and all-cause mortality over a median follow-up of 5.8 years.

Specifically, patients with hs-cTnI concentrations ≥10 ng/L or hs-cTnT ≥16 ng/L had a 5-year MACE rate of 33%, similar to those who presented with MACE, indicating that even low levels of these biomarkers can signal serious long-term health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detectable High-Sensitivity Cardiac Troponin within the Population Reference Interval Conveys High 5-Year Cardiovascular Risk: An Observational Study. Than, MP., Aldous, SJ., Troughton, RW., et al.[2019]

In a study of 78 women undergoing anthracycline-based chemotherapy for breast cancer, high-sensitivity cardiac troponin I (hs-cTnI) levels were found to increase significantly after each treatment cycle, indicating cumulative cardiotoxicity.

Measuring hs-cTnI levels before treatment cycles was more effective in predicting myocardial injury than measuring them after treatment, highlighting the importance of early detection in managing chemotherapy-related heart damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic Changes in High-Sensitivity Cardiac Troponin I in Response to Anthracycline-Based Chemotherapy. Tzolos, E., Adamson, PD., Hall, PS., et al.[2021]

A 72-year-old patient with metastatic melanoma treated with immune checkpoint inhibitors developed elevated levels of high-sensitivity cardiac troponin T (hs-cTnT) due to ICI-induced myositis, rather than myocarditis, highlighting the importance of distinguishing between these conditions.

Comprehensive cardiac evaluations, including echocardiography and cardiac magnetic resonance imaging, along with normal cardiac troponin I levels, helped confirm the absence of myocarditis, suggesting that elevated hs-cTnT can occur without cardiac injury in patients receiving ICI therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report of elevation of high-sensitivity cardiac troponin T in the absence of cardiac involvement in immune checkpoint inhibitor-associated myositis. Ruperti-Repilado, FJ., van der Stouwe, JG., Haaf, P., et al.[2022]

The high sensitivity cardiac troponin I (hs-cTnI) assay demonstrated a significantly lower critical outlier rate and higher detection rates compared to the conventional troponin I (cTnI) assay, indicating improved diagnostic capabilities for myocardial infarction.

While the hs-cTnI assay showed fewer false negatives, it also had a higher rate of false positives, especially when using gender-specific cut-offs, highlighting the need for careful clinical verification and interpretation of results in practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transitioning high sensitivity cardiac troponin I (hs-cTnI) into routine diagnostic use: More than just a sensitivity issue. Lee, GR., Browne, TC., Guest, B., et al.[2020]

In a study of 30 patients undergoing immune checkpoint inhibitor therapy, baseline levels of high-sensitivity troponin T (hs-TnT) were found to predict cardiovascular risks, with a cut-off of 14 ng/L indicating a higher likelihood of serious cardiovascular events after 3 months.

Patients with hs-TnT levels ≥14 ng/L before treatment were more likely to experience cardiovascular complications, such as death, stroke, or new heart failure, highlighting the importance of monitoring hs-TnT levels in patients receiving ICIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-treatment high-sensitivity troponin T for the short-term prediction of cardiac outcomes in patients on immune checkpoint inhibitors. Petricciuolo, S., Delle Donne, MG., Aimo, A., et al.[2021]

High-sensitivity cardiac troponin T (hs-cTnT) is more closely associated with renal dysfunction and is a stronger predictor of overall cardiovascular health and mortality compared to high-sensitivity cardiac troponin I (hs-cTnI).

Conversely, hs-cTnI is more sensitive to detecting coronary artery disease and ischemic events, suggesting that the choice between hs-cTnT and hs-cTnI could be important for personalized cardiac assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences between high-sensitivity cardiac troponin T and I in stable populations: underlying causes and clinical implications. Eggers, KM., Hammarsten, O., Lindahl, B.[2023]

Cardiac troponins I (cTnI) and T (cTnT) are established biomarkers for detecting heart injury and diagnosing myocardial infarction, with high-sensitivity (hs) assays providing improved detection of low troponin levels.

This mini-review discusses critical analytical questions regarding hs troponin assays, including how they are defined, the importance of establishing healthy reference populations, and the challenges in standardizing these assays for consistent clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analytical characteristics of high-sensitivity cardiac troponin assays. Apple, FS., Collinson, PO.[2022]

In a study of 1068 patients with stable coronary heart disease followed for 13 years, both high-sensitivity troponin T (hs-cTnT) and troponin I (hs-cTnI) were found to be significant predictors of recurrent cardiovascular disease (CVD) events, particularly in the top quartiles of their concentrations.

However, when adjusting for other emerging biomarkers, the predictive power of hs-cTnT and hs-cTnI diminished, suggesting that while they are useful indicators, their effectiveness may be influenced by the presence of additional biomarkers related to cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hs-cTroponins for the prediction of recurrent cardiovascular events in patients with established CHD - A comparative analysis from the KAROLA study. Jansen, H., Jänsch, A., Breitling, LP., et al.[2018]

High-sensitivity cardiac troponin T and I (hs-cTnT/I) levels can predict significant health risks, with a 23% increased risk of all-cause death for each standard deviation increase in hs-cTn, based on a review of 24 studies involving over 203,000 subjects.

Hs-cTn levels are also strong indicators for cardiovascular death, cardiovascular events, and heart failure hospitalization, demonstrating their importance in assessing heart health in the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-sensitivity troponins for outcome prediction in the general population: a systematic review and meta-analysis. Aimo, A., Georgiopoulos, G., Panichella, G., et al.[2022]

In a study of 45 patients with early-stage left-sided breast cancer undergoing radiotherapy, 26.6% experienced a significant increase in cardiac troponin T (Hs-cTnT) levels, indicating potential myocardial damage during treatment.

The increase in Hs-cTnT was associated with the radiation dose to the heart, particularly the volume of heart tissue exposed (V5), suggesting that monitoring Hs-cTnT could help assess cardiac risk in patients receiving radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

V5 and High Sensitivity Cardiac Troponin T for Early Detection of Cardiac Toxicity During Left Breast Cancer Irradiation. Cirnigliaro, V., Pietrosanti, S., Demofonti, C., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Detectable High-Sensitivity Cardiac Troponin within the Population Reference Interval Conveys High 5-Year Cardiovascular Risk: An Observational Study. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Dynamic Changes in High-Sensitivity Cardiac Troponin I in Response to Anthracycline-Based Chemotherapy. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Case report of elevation of high-sensitivity cardiac troponin T in the absence of cardiac involvement in immune checkpoint inhibitor-associated myositis. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Transitioning high sensitivity cardiac troponin I (hs-cTnI) into routine diagnostic use: More than just a sensitivity issue. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Pre-treatment high-sensitivity troponin T for the short-term prediction of cardiac outcomes in patients on immune checkpoint inhibitors. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Differences between high-sensitivity cardiac troponin T and I in stable populations: underlying causes and clinical implications. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Analytical characteristics of high-sensitivity cardiac troponin assays. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Hs-cTroponins for the prediction of recurrent cardiovascular events in patients with established CHD - A comparative analysis from the KAROLA study. [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

High-sensitivity troponins for outcome prediction in the general population: a systematic review and meta-analysis. [2022]

10. Greece pubmed.ncbi.nlm.nih.gov

V5 and High Sensitivity Cardiac Troponin T for Early Detection of Cardiac Toxicity During Left Breast Cancer Irradiation. [2023]