PROactive Evaluation of Function to Avoid CardioToxicity

NCT03862131 | Terminated Phase 2 Results DMC FDA Device

• 1 other identifier: 201809177
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

This study is intended to evaluate the ability of an intramyocardial strain analysis package with cardiac MRI to assist in the early detection and management of cardiotoxicity from therapeutics used to treat cancer.

Conditions

Cardiotoxicity; Breast Cancer; Lymphoma; Sarcoma; Leukemia; Myeloma; Lung Cancer

Outcome Measures

Primary Outcomes (5)

• ROC AUC of MyoStrain® Compared to Standard CMR Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment

  The area under the curve refers to the area under the curve of Receiver operating characteristic curves (ROC AUC) to evaluate the accuracy of MyoStrain® to detect cardiotoxicity compared to Cardiovascular Magnetic Resonance (CMR) Imaging standard measurements. * Myocardial dysfunction was defined as the occurrence of either clinical or subclinical cardiotoxicity. * Clinical cardiotoxicity was defined as an absolute change in LVEF \> 10% from baseline to below 53% combined with heart failure symptoms or elevation in NT pro BNP to above 199 pg/mL. * In patients with LVEF \< 53% at baseline, clinical cardiotoxicity was defined by a symptomatic drop in LVEF \> 10% or a HF hospitalization. * Subclinical CTX was defined as an asymptomatic patient with a greater than 10% decrease in LVEF, worsening GLS more than 15% from baseline, or new elevation in NT pro BNP \>199 pg/mL.

  Through 36 months

• Sensitivity of MyoStrain® Compared to CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment

  Sensitivity is defined as the number of true positives divided by the number of true positives + number of false negatives. * Myocardial dysfunction was defined as the occurrence of either clinical or subclinical cardiotoxicity. * Clinical cardiotoxicity was defined as an absolute change in LVEF \> 10% from baseline to below 53% combined with heart failure symptoms or elevation in NT pro BNP to above 199 pg/mL. * In patients with LVEF \< 53% at baseline, clinical cardiotoxicity was defined by a symptomatic drop in LVEF \> 10% or a HF hospitalization. * Subclinical CTX was defined as an asymptomatic patient with a greater than 10% decrease in LVEF, worsening GLS more than 15% from baseline, or new elevation in NT pro BNP \>199 pg/mL

  Through 36 months

• Specificity of MyoStrain® and CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment

  Specificity is defined as the number of true negatives divided by the number of true negatives + number of false positives. * Myocardial dysfunction was defined as the occurrence of either clinical or subclinical cardiotoxicity. * Clinical cardiotoxicity was defined as an absolute change in LVEF \> 10% from baseline to below 53% combined with heart failure symptoms or elevation in NT pro BNP to above 199 pg/mL. * In patients with LVEF \< 53% at baseline, clinical cardiotoxicity was defined by a symptomatic drop in LVEF \> 10% or a HF hospitalization. * Subclinical CTX was defined as an asymptomatic patient with a greater than 10% decrease in LVEF, worsening GLS more than 15% from baseline, or new elevation in NT pro BNP \> 199 pg/mL

  Through 36 months

• Accuracy of MyoStrain® and CMR Standard Measurements (LV End Diastolic Volume Index, LV End Systolic Volume Index, LV Stroke Volume Index and Left Ventricular Ejection Fraction) to Detect Myocardial Dysfunction During Cancer Treatment

  Accuracy is defined as (true positives + true negatives) divided by the total number of cases * Myocardial dysfunction was defined as the occurrence of either clinical or subclinical cardiotoxicity. * Clinical cardiotoxicity was defined as an absolute change in LVEF \> 10% from baseline to below 53% combined with heart failure symptoms or elevation in NT pro BNP to above 199 pg/mL. * In patients with LVEF \< 53% at baseline, clinical cardiotoxicity was defined by a symptomatic drop in LVEF \> 10% or a HF hospitalization. * Subclinical CTX was defined as an asymptomatic patient with a greater than 10% decrease in LVEF, worsening GLS more than 15% from baseline, or new elevation in NT pro BNP \>199 pg/mL.

  Through 36 months

• Independent Effectiveness of MyoStrain® to Detect Cardiac Dysfunction Compared to Standard Cardiac Imaging Measures

  Myocardial dysfunction is the occurrence of either clinical or subclinical cardiotoxicity. * Clinical cardiotoxicity was defined as an absolute change in LVEF \>10% from baseline to below 53% combined with heart failure symptoms or elevation in NT pro BNP to above 199 pg/mL * In patients with LVEF \<53% at baseline, clinical cardiotoxicity was defined by a symptomatic drop in LVEF \>10% or a HF hospitalization * Subclinical CTX was defined as an asymptomatic patient with a greater than 10% decrease in LVEF, worsening GLS more than 15% from baseline, or new elevation in NT pro BNP \>199 pg/mL

  Through 36 months

Study Arms (2)

MyoStrain® unblinded treatment arm

EXPERIMENTAL

* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk Group * The unblinded treatment arm will enhance patient management by augmenting standard of care with serial MyoStrain® monitoring of the impact of cancer therapy on myocardial function. * Higher Risk unblinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit. * In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.

Device: MyoStrain®

MyoStrain® blinded control arm

ACTIVE COMPARATOR

* After consenting to the PROACT study, patients will undergo a baseline MRI to determine their risk stratification for the study. This baseline MyoStrain® MRI must demonstrate 2 or more segments measuring \>-10% or 9 or more segments \>-17% for entrance into the study as the Higher Risk group * The blinded control arm will provide investigators with LVEF and LVEDV/LVESV measurements, which are clinical, in conjunction with standard of care * Higher Risk blinded patients will continue to undergo MyoStrain® MRI testing, regardless of study arm, at 1 month (+1 week), 3 months (+ 1 week), 6 months (+1 week), 12 months (+ 30 days), 24 months (+30 days), and 36 months (+30 days) after the baseline visit. * In addition to the MyoStrain® testing, patients will also be asked to complete a brief patient satisfaction questionnaire at each PROACT time point.

Device: MyoStrain®

Interventions

MyoStrain® DEVICE

MyoStrain® SENC software receives image data from MRI storage archives and performs viewing, image manipulation, communication, printing, and quantification of images.

Also known as: Cardiac MRI Imaging Software, Intramyocardial Strain

MyoStrain® blinded control arm; MyoStrain® unblinded treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant in the SURVIVE registry
• Signed informed consent form for PROACT
• Histological diagnosis of any cancer type (patients with treated and clinically stable brain metastasis are acceptable)
• Scheduled to receive anti-cancer therapy (radiation therapy is permitted)

You may not qualify if:

• Contraindication to magnetic resonance imaging (MRI)
• Unable to comply with study investigations (in the judgment of the investigator)
• Life expectancy less than 1 year
• Note: If a patient develops a temporary contraindication (e.g. temporary tissue expanders in breast cancer patients) after the baseline MRI, follow up MRIs will be discontinued for safety for the duration in which the patient has the contraindication. However, once the patient is no longer contraindicated to receiving MRIs, the study schedule may resume with their next scheduled MRI time point from the date of enrollment. Therefore, some time points may be skipped during the patient's enrollment in the study.
• Also, if a patient needs a repeat MRI at any time point for any reason (i.e. panic attack during the MRI causing them to not be able to continue, unreadable images, etc.), we may repeat the MRI as long as the patient is willing.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Myocardial Solutions: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (2)

• Daniel J. Lenihan, Gregory M. Lanza, Pamela K. Woodard, Joshua Mitchell, SUPERIOR DETECTION OF CARDIOTOXICITY USING CARDIAC MRI MYOSTRAIN DURING CANCER CHEMOTHERAPY, Journal of the American College of Cardiology, Volume 83, Issue 13, Supplement, 2024, Page 2350, ISSN 0735-1097, https://doi.org/10.1016/S0735-1097(24)04340-7. (https://www.sciencedirect.com/science/article/pii/S0735109724043407)

  RESULT

• Joshua Mitchell, Syed Z. Qamer, Gregory M. Lanza, Pamela K. Woodard, JAMES WHAYNE, Daniel J. Lenihan, MYOCARDIAL STRAIN GUIDED CARDIOPROTECTION DURING CHEMOTHERAPY WITH CARDIAC MRI IMPROVES CARDIAC HEALTH, Journal of the American College of Cardiology, Volume 83, Issue 13, Supplement, 2024, Page 2673, ISSN 0735-1097, https://doi.org/10.1016/S0735-1097(24)04663-1. (https://www.sciencedirect.com/science/article/pii/S0735109724046631)

  RESULT

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Cardiotoxicity; Breast Neoplasms; Lymphoma; Sarcoma; Leukemia; Neoplasms, Plasma Cell; Lung Neoplasms

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Hematologic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Joshua Mitchell
• Organization: Washington University School of Medicine

jdmitchell@wustl.edu

314-362-1291

Study Officials

• Joshua Mitchell, M.D., MSCI, FACC, FICOS

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Patients will be classified based on baseline segmental MyoStrain Fast-SENC strain testing, into lower and higher risk groups. The higher risk group will be randomized with half blinded and half unblinded to intramyocardial strain in terms of assessing cardiotoxicity incidence and management. Physicians will have knowledge of MyoStrain intramyocardial strain and cardiac MRI information in the unblinded group to augment standard of care in detecting and managing cardiotoxicity. Physicians will not have access to or knowledge of intramyocardial strain and cardiac MRI data, except 4 standard cardiac measures, for patients in the blinded group.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2019
• First Posted: March 5, 2019
• Study Start: March 13, 2019
• Primary Completion: June 14, 2024
• Study Completion: June 14, 2024
• Last Updated: July 29, 2025
• Results First Posted: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)