JUdicious Surveillance for Trastuzumab Induced Cardiotoxicity in the First Year

NCT06930521 | Not Yet Recruiting DMC

• 1 other identifier: 5034
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

This study focuses on male and female patients being treated for breast cancer that is positive for the HER2 receptor which requires special treatments targeting that receptor. The problem is that these treatments, while effective for the cancer, can sometimes harm the heart. Because of this, patients have to undergo heart tests every three months during treatment, even if they have no history of heart disease or feel fine. The guidelines for these regular heart tests were established decades ago when these treatments were first introduced, but research shows that most of these tests don't actually change the treatment plan. This suggests that many patients are going through unnecessary tests, which can cause stress, delay treatments, and increase healthcare costs. To address this, the researchers propose a new study with 300 patients with HER2 positive breast cancer to test a more personalized approach to cardiac surveillance. Participants will be classified based on their risk of heart problems: low or intermediate. Instead of testing every patient every three months, those in the intermediate group will be tested every 4 months, and those in the low-risk group will be tested every 6 months. The researchers will compare this new approach to the current system to see if fewer tests are just as safe and effective. The researchers will measure heart health, how well cancer treatments are completed, and how patients feel about having fewer tests. If this new approach works, it could save money and reduce the burden on female patients without risking their health.

Conditions

Cardiovascular Health; Breast Cancer; Breast Cancer Early Stage Breast Cancer (Stage 1-3); Cardio-oncology; Circulatory and Respiratory Health; Clinical and Translational Cardiovascular Sciences; Health Services and Systems - Healthcare Effectiveness &Amp; Outcomes

Keywords

Trastuzumab; Cardiac imaging; Her-2 positive breast cancer; Echocardiography; Cardiotoxicity; Left ventricular ejection fraction; Heart failure; Randomized controlled trial; Nuclear imaging; Non-inferiority

Outcome Measures

Primary Outcomes (1)

• Hierarchical composite endpoint encompassing heart health, patient well-being, treatment completion, and imaging frequency in combination, while assessing priority to more important measures.

  The primary outcome is a hierarchical composite endpoint for patients with BC receiving HER2-targeted therapy (HER2TT). Participant in the intervention group is compared to participants in the control group based on the following outcomes, in order: 1. Clinically overt heart failure (determined as a binary event Y/N, per standardized definition) 2. Premature discontinuation of HER2TT (determined as a binary event Y/N, per clinical records) 3. Patient-reported outcome measures (PROM) of anxiety/depression, stress and treatment burden: desirable outcome is a better scores in ≥2 of 3 PROMs-Treatment Burden Questionnaire, Hospital Anxiety and Depression Scale, Perceived Stress Scale 4. Asymptomatic cardiotoxicity at end of HER2TT (per criteria, based on LVEF change from baseline to 12 months echocardiograms) 5. Time to complete HER2TT (shorter is better)-number of weeks between 1st and last HER2TT 6. Total cardiac imaging tests during HER2TT (fewer is better)-total assessments of LVEF

  From enrollment to the end of treatment at 48 weeks

Study Arms (2)

Standard of Care

NO INTERVENTION

The SOC arm will receive imaging before cycles 1, 5, 9, and 13 (in keeping with the FDA product label), then at the end of HER2-TT, i.e., imaging every 3 months for uninterrupted adjuvant HER2TT.

Judicious Imaging

EXPERIMENTAL

This group will get less echocardiograms based on their risk of developing heart failure. People who do not have any issues that predispose to heart failure are categorized as low risk and will get an echocardiogram once every 6 months. People who have factors that may predispose to heart failure are categorized as intermediate risk and will get an echocardiogram approximately once every 4 months.

Diagnostic Test: Intervention - Low Risk Group OR Intermediate Risk Group

Interventions

Intervention - Low Risk Group OR Intermediate Risk Group DIAGNOSTIC_TEST

Participants will be randomized to judicious imaging (decreased imaging frequency based on HF risk category) or SOC (imaging every 3 months). Participants who do not have any HF risk factors will be categorized as low risk, while participants with at least one risk factor will be categorized as intermediate risk for HF. Low Risk (zero risk factors): imaging before cycles 1 and 9 of HER2-TT (i.e., at baseline and near the halfway mark, corresponding to 2 fewer studies than SOC in Year 1), then after the end of HER2TT. This translates to imaging every 6 months for uninterrupted adjuvant HER2TT. Intermediate Risk (any risk factors): imaging before cycles 1, 6, and 12 of HER2-TT (i.e., at baseline and near the 1/3 and 2/3 marks, corresponding to 1 fewer study than SOC in Year 1), then at end of HER2TT. This translates to imaging every 4 months for uninterrupted adjuvant HER2TT.

Judicious Imaging

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage 1-3 breast cancer (BC).
• Age 18-79 years.
• HER-2 positive BC with planned HER2 targeted therapy (HER2TT) for curative intent.

You may not qualify if:

• Distant metastases detected clinically, radiographically, or histologically
• Baseline echocardiogram images of insufficient quality for a quantitative assessment of left ventricular ejection fraction (LVEF)
• Pre-existing cardiovascular disease, defined as:
• Prior myocardial infarction (even if LVEF has normalized)
• Prior heart failure (HF, including patients with preserved ejection fraction and normalized LVEF)
• Baseline LVEF \<55%
• Atrial fibrillation
• Greater than moderate valvular disease (i.e., severe, or moderate-severe)
• Cumulative anthracycline exposure ≥250mg/m2 before starting HER2TT
• New York Heart Association Functional Class II, III or IV, or Eastern Cooperative Oncology Group score \>2\*

Sponsors & Collaborators

• Women's College Hospital: lead
• University Health Network, Toronto: collaborator

Study Sites (1)

Women's College Hospital

Toronto, Ontario, M5S 1B2, Canada

Location

MeSH Terms

Conditions

Breast Neoplasms; Cardiotoxicity; Heart Failure

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; 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

Central Study Contacts

Husam Abdel-Qadir, MD, PhD, FRCPC

CONTACT

416-323-7723; husam.abdel-qadir@wchospital.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiologist

Model Details: Participants will be randomized to one of two groups with regards to the frequency of mandatory echocardiograms: Group 1 - Standard of Care Group: Participants in this group will receive imaging before cycles 1, 5, 9, and 13 of trastuzumab (or every 3 months) and another echocardiogram after completion of trastuzumab (within 100 days after completion of HER2TT). Group 2 - Judicious Imaging Group: This group will get less echocardiograms based on their risk of developing heart failure. People who do not have any issues that predispose to heart failure are categorized as low risk and will get an echocardiogram once every 6 months. People who have factors that may predispose to heart failure are categorized as intermediate risk and will get an echocardiogram approximately once every 4 months.

Study Record Dates

• First Submitted: March 31, 2025
• First Posted: April 16, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2033
• Last Updated: April 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)