Stress Echocardiography to Identify Chemotherapy Induced Cardiotoxicity in Cancer Patients With Heart Failure Risk

Evaluating Changes in Cardiac Function During Stress Echocardiography for the Identification of Chemotherapy Induced Cardiotoxicity in Cancer Patients at Risk of Developing Heart Failure

This clinical trial evaluates changes in cardiac (heart) function during stress echocardiography to screen for chemically induced cardiotoxicity in cancer patients at a high risk for developing heart failure. Some chemotherapeutic agents to treat certain types of cancers can induce cardiac dysfunction and heart failure. Currently there is no validated means of predicting which patients will go on to develop cardiac toxicity and heart failure following treatment with chemotherapeutic agents. Stress echocardiography is a test that uses ultrasound imaging to show how well the heart muscle is working to pump blood to the body during low intensity exercise. Stress echocardiography prior to and during cancer treatment may help doctors find cancer therapeutic related cardiac dysfunction sooner when it may be easier to treat.

Study Overview

• Status: Completed
• Conditions: Malignant Solid Neoplasm; Hematopoietic and Lymphoid System Neoplasm
• Intervention / Treatment: Other: Questionnaire Administration; Other: Electronic Health Record Review; Procedure: Echocardiography; Procedure: Stress Echocardiography

Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether changes in the following parameters of cardiac function at rest or with low intensity exercise occur following (1) treatment with cancer therapeutics or (2) cardiac rehabilitation:

Ia. 2-Dimensional (2D) and 3-dimensional (3D) left ventricular (LV) longitudinal strain and strain rate; Ib. Right ventricular (RV) longitudinal strain and strain rate; Ic. LV circumferential and radial strain and strain rate; Id. 2D and 3D wall motion; Ie. 2D and 3D volumetric left ventricular ejection fraction (LVEF); If. Mitral valve inflow velocities (E, A) and mitral annular tissue Doppler (e', a'); Ig. Tricuspid tissue velocities and tricuspid annular plane systolic excursion (TAPSE).

SECONDARY OBJECTIVES:

I. To determine whether changes after treatment with cancer therapeutics or a period of cardiac rehabilitation in any of the aforementioned parameters of cardiac function with low intensity exercise:

Ia. Occur before changes in resting strain or resting LVEF; Ib. Predict future reductions in LVEF (cardiotoxicity) or in the case of cardiac rehabilitation, prevention of LVEF decrease; Ic. Predict the development of clinical heart failure.

OUTLINE: Participants are assigned to 1 of 2 groups.

GROUP I (CASE): Patients choose to undergo either a resting echocardiography performed before and after delivery of a cancer therapeutic agent and months 3, 6, 9 and 12 or up to 5 low intensity stress echocardiography over 25 minutes performed depending on where they are at in the course of their cancer therapy and/or cardiac rehabilitation program at baseline and/or months 3, 6, 9 and 12 after starting cancer therapy.

GROUP II (CONTROL): Participants undergo low intensity stress echocardiography over 25 minutes at baseline and may undergo a second one at least 24 hours later.

After completion of study intervention, patients in Group 1 are followed up at 2, 5, and 10 years.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Current or previous diagnosis of solid organ cancers (breast, non-small cell lung, rectal, renal, hepatic cancer, metastatic melanoma, sarcoma) or hematological disease (lymphoma, leukemia, multiple myeloma, monoclonal gammopathy of undetermined significance [MGUS])
• Age >= 18 years at study enrollment

• Plan to receive, or history of having received, chemotherapy (anthracycline, alkylating agent [cyclophosphamide, ifosfamide], and/or antimicrotubule agent [docetaxel, paclitaxel]) with or without specific targeted therapies;

  • Anti-HER2 targeted therapies (trastuzumab, pertuzumab)
  • Vascular endothelial growth factor (VEGF) inhibitors (bevacizumab, sunitinib, sorafenib, pazopanib, axitinib, vandetanib)
  • Immune checkpoint inhibitors (ipilimumab, nivolumab, pembrolizumab)
• Plan to undergo conditioning chemotherapy for bone marrow transplantation (autologous/allogeneic)

Exclusion Criteria:

• Coronary artery disease
• Significant (more than mild) valvular heart disease
• Pre-existing heart failure
• Pre-existing cardiomyopathy
• Musculoskeletal or neurologic abnormality prohibiting low intensity exercise on a stationary bicycle
• Severe pulmonary disease limiting ability to perform low intensity exercise on a stationary bicycle

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I (resting and/or stress echocardiography); Patients choose to undergo either a resting echocardiography performed before and after delivery of a cancer therapeutic agent and months 3, 6, 9 and 12 or up to 5 low intensity stress echocardiography over 25 minutes performed depending on where they are at in the course of their cancer therapy and/or cardiac rehabilitation program at baseline and/or months 3, 6, 9 and 12 after starting cancer therapy.	Other: Questionnaire Administration; Ancillary studies; Other: Electronic Health Record Review; Ancillary studies; Procedure: Echocardiography; Undergo resting echocardiography; Other Names: EC; Procedure: Stress Echocardiography; Undergo stress echocardiography; Other Names: Stress Echo
Active Comparator: Group II (stress echocardiography); Participants undergo low intensity stress echocardiography over 25 minutes at baseline and may undergo a second one at least 24 hours later.	Procedure: Stress Echocardiography; Undergo stress echocardiography; Other Names: Stress Echo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in cardiac function with low intensity exercise in cancer patients	Resting echocardiography will be performed immediately before and after patient receives cancer therapeutic treatment. Up to five sessions of low intensity stress echocardiograms will be performed during the course of the study depending on where they are in the course of cancer therapy and/or cardiac rehabilitation program at study enrollment. Patients may opt to change from low intensity echocardiogram to resting echocardiogram during the course of the study.	Baseline to 12 months
Changes in cardiac function with low intensity exercise in cancer patients after treatment with cancer therapeutics.	Resting echocardiography will be performed immediately before and after patient receives cancer therapeutic treatment. Up to five sessions of low intensity stress echocardiograms will be performed by during the course of the study depending on where they are in the course of cancer therapy and/or cardiac rehabilitation program at study enrollment. Patients may opt to change from low intensity echocardiogram to resting echocardiogram during the course of the study. D	Baseline to 12 months
Changes in cardiac function with low intensity exercise in cancer patients after a period of cardiac rehabilitation.	Resting echocardiography will be performed immediately before and after patient receives cancer therapeutic treatment. Up to five sessions of low intensity stress echocardiograms will be performed by during the course of the study depending on where they are in the course of cancer therapy and/or cardiac rehabilitation program at study enrollment. Patients may opt to change from low intensity echocardiogram to resting echocardiogram during the course of the study.	Baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reductions in left ventricular ejection fraction (LVEF)	Data will be collected from chart reviews and patient surveys. Predictors of reductions in LVEF will be assessed using linear regression and multiple linear regression analyses. A p-value < 0.05 will define significance. Cancer Therapeutics-Related Cardiac Dysfunction will be defined as per recent guidelines as a drop in LVEF of > 10% to < 53%.	Up to 10 years
Reductions in onset of clinical heart failure	Data will be collected from chart reviews and patient surveys. Predictors of reductions in heart failure will be assessed using linear regression and multiple linear regression analyses. A p-value < 0.05 will define significance. Heart failure will be defined as a diagnosis made by one of the patients treating physicians.	Up to 10 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Hector R Villarraga, M.D., Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2015
• Primary Completion (Actual): March 19, 2024
• Study Completion (Actual): March 19, 2024

Study Registration Dates

• First Submitted: July 10, 2023
• First Submitted That Met QC Criteria: July 10, 2023
• First Posted (Actual): July 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Wounds and Injuries; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Heart Failure; Neoplasms; Cardiotoxicity
• Other Study ID Numbers: 15-002855 (Other Identifier: Mayo Clinic in Rochester); NCI-2022-10806 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No