Cardiac Magnetic Resonance Monitoring of Immune Checkpoint Inhibitor-related Cardiotoxicity

Official title

Cardiac Magnetic Resonance Monitoring of Immune Checkpoint Inhibitor-related Cardiotoxicity in Patients With Gynecologic Malignancies: A Cohort Study

Overview

This study is a prospective cohort clinical research that analyzes the changes in CMR parameters before and after immune checkpoint inhibitors (ICIs) therapy in patients with gynecologic malignancies. It also evaluates the value of CMR parameters in predicting long-term outcomes. The baseline assessment will be conducted prior to ICIs treatment, followed by multiple assessments during the medication process including within one week prior to cycle 3 , within the week prior to cycle 5 , 1 year after the first dose, and 2 years after the first dose. Assessment will also be conducted after discontinuation of ICIs medication. The assessment includes clinical assessment, CMR imaging, echocardiography, serum cardiac injury biomarkers, etc. Cancer therapy-related cardiac dysfunction (CTRCD), survival, and major adverse cardiac events (MACE) will be followed up.

Interventions

• Diagnostic test Cardiac magnetic resonance
  Cardiac magnetic resonance protocols include cine, non-contrast T1-mapping and T2-mapping.

Primary outcome measures

• cancer therapy-related cardiac dysfunction (CTRCD) [Time frame: 2 month to 3 years]

Secondary outcome measures (1)

• All-cause death; major adverse cardiac events (MACE) [Time frame: 2 month to 3 years]

Eligibility criteria

Inclusion criteria

• 1\. Female patients aged 18 to 75 years, diagnosed with gynecological malignancies through histology or cytology.
• 2\. Patients who are preparing for monotherapy or combination therapy with ICIs.
• 3\. Voluntary signing of informed consent form.
• 4\. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 5\. Expected survival of at least 6 months.

Exclusion criteria

• 1\. Previously received ICIs treatment.
• 2\. With allergies or contraindications to ICIs.
• 3\. Confirmed to be brain metastasis.
• 4\. Patients who have major surgery within 4 weeks prior to or following the screening period.
• 5\. Patients who have received systemic corticosteroids (at a dose equivalent to >10 mg prednisone per day) or other immunosuppressive medications within 14 days prior to enrollment or during the study period; however, the following situations are allowed for inclusion:

• the use of topical or inhaled corticosteroids is permitted;
• short-term (≤7 days) use of corticosteroids for prevention or treatment of non-autoimmune diseases is allowed.
• 6\. Left ventricular ejection fraction (LVEF) ≤50%, or New York Heart Association functional classification (NYHA) ≥III.
• 7\. Coronary heart disease, cardiomyopathy, congenital heart disease, valvular heart disease and pericardial diseases with confirmed diagnosis.
• 8\. Lack of autonomous capacity, or a documented history of mental disease.
• 9\. MRI contraindications: Pacemakers, neurostimulators, artificial metal heart valves, arterial aneurysm clips, intraocular metallic foreign bodies, inner ear implants, metal prostheses, metal limbs, metal joints, and any other metallic implants or foreign objects; severe hyperthermia patients; claustrophobia; severe respiratory conditions that prevent breath-holding.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Study design

Observational model

Cohort

Study locations

China · 1 center

• West China Second University Hospital — Chengdu

Publications

• Zhang L, Zlotoff DA, Awadalla M, Mahmood SS, Nohria A, Hassan MZO, Thuny F, Zubiri L, Chen CL, Sullivan RJ, Alvi RM, Rokicki A, Murphy SP, Jones-O'Connor M, Heinzerling LM, Barac A, Forrestal BJ, Yang EH, Gupta D, Kirchberger MC, Shah SP, Rizvi MA, Sahni G, Mandawat A, Mahmoudi M, Ganatra S, Ederhy S, Zatarain-Nicolas E, Groarke JD, Tocchetti CG, Lyon AR, Thavendiranathan P, Cohen JV, Reynolds KL, PMID 32539614
• Thavendiranathan P, Zhang L, Zafar A, Drobni ZD, Mahmood SS, Cabral M, Awadalla M, Nohria A, Zlotoff DA, Thuny F, Heinzerling LM, Barac A, Sullivan RJ, Chen CL, Gupta D, Kirchberger MC, Hartmann SE, Weinsaft JW, Gilman HK, Rizvi MA, Kovacina B, Michel C, Sahni G, Gonzalez-Mansilla A, Calles A, Fernandez-Aviles F, Mahmoudi M, Reynolds KL, Ganatra S, Gavira JJ, Gonzalez NS, Garcia de Yebenes Castro PMID 33766256
• Cadour F, Cautela J, Rapacchi S, Varoquaux A, Habert P, Arnaud F, Jacquier A, Meilhac A, Paganelli F, Lalevee N, Scemama U, Thuny F. Cardiac MRI Features and Prognostic Value in Immune Checkpoint Inhibitor-induced Myocarditis. Radiology. 2022 Jun;303(3):512-521. doi: 10.1148/radiol.211765. Epub 2022 Mar 1. PMID 35230185
• Zhang L, Awadalla M, Mahmood SS, Nohria A, Hassan MZO, Thuny F, Zlotoff DA, Murphy SP, Stone JR, Golden DLA, Alvi RM, Rokicki A, Jones-O'Connor M, Cohen JV, Heinzerling LM, Mulligan C, Armanious M, Barac A, Forrestal BJ, Sullivan RJ, Kwong RY, Yang EH, Damrongwatanasuk R, Chen CL, Gupta D, Kirchberger MC, Moslehi JJ, Coelho-Filho OR, Ganatra S, Rizvi MA, Sahni G, Tocchetti CG, Mercurio V, Mahmoudi PMID 32112560
• Faron A, Isaak A, Mesropyan N, Reinert M, Schwab K, Sirokay J, Sprinkart AM, Bauernfeind FG, Dabir D, Pieper CC, Heine A, Kuetting D, Attenberger U, Landsberg J, Luetkens JA. Cardiac MRI Depicts Immune Checkpoint Inhibitor-induced Myocarditis: A Prospective Study. Radiology. 2021 Dec;301(3):602-609. doi: 10.1148/radiol.2021210814. Epub 2021 Sep 28. PMID 34581628
• Liu J, Cao Y, Zhu K, Yao S, Yuan M, Kong X, Liu X, Li Y, Cui Y, Han X, Zhou X, Meng R, Shi H. Early evaluation of subclinical cardiotoxicity in patients with lung cancer receiving immune checkpoint inhibitors by cardiovascular magnetic resonance: a prospective observational study. Quant Imaging Med Surg. 2022 Oct;12(10):4771-4785. doi: 10.21037/qims-22-41. PMID 36185042
• Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, Kindermann I, Gutberlet M, Cooper LT, Liu P, Friedrich MG. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. J Am Coll Cardiol. 2018 Dec 18;72(24):3158-3176. doi: 10.1016/j.jacc.2018.09.072. PMID 30545455

Identifiers

NCT: NCT06132984 · WestChinaSUH2022228

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗