Surveillance for Cardiotoxicity from Trastuzumab in Breast Cancer

(JUSTIFY Trial)

Overseen By Husam Abdel-Qadir, MD, PhD, FRCPC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Women's College Hospital

Must be taking: HER2 targeted therapy

Disqualifiers: Metastases, Cardiovascular disease, Anthracyclines, others

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

Compensation: Varies

Number of Visits: 3

Duration: 48 weeks

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It focuses on monitoring heart health during cancer treatment.

Is trastuzumab generally safe for humans?

Trastuzumab, used for treating certain types of breast cancer, has been linked to heart problems in some patients. Studies show that a small percentage of people experience serious heart issues, especially older patients, but it is generally considered safe for many users. ^{1 2 3 4 5}

How does the treatment for cardiotoxicity surveillance in breast cancer differ from other treatments?

This treatment is unique because it focuses on monitoring heart health in patients receiving trastuzumab, a drug used for HER2-positive breast cancer, which can cause heart problems. It categorizes patients into low or intermediate risk groups to tailor the monitoring approach, unlike standard treatments that may not differentiate based on risk levels. ^{2 3 4 6 7}

What data supports the effectiveness of the drug trastuzumab in breast cancer treatment?

The research highlights that trastuzumab is effective for treating HER2-positive breast cancer, but it can cause heart-related side effects. Monitoring heart function is important to manage these risks while benefiting from the drug's cancer-fighting properties. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for male and female patients with HER2 positive breast cancer. It's designed to test a new approach to monitoring heart health during cancer treatment, which can sometimes harm the heart. Patients will be categorized into low or intermediate risk groups for cardiotoxicity.

Inclusion Criteria

My breast cancer is at stage 1, 2, or 3.

My breast cancer is HER2 positive and I plan to undergo HER2 targeted therapy.

Exclusion Criteria

Baseline echocardiogram images of insufficient quality for a quantitative assessment of left ventricular ejection fraction (LVEF)

My cancer has spread to distant parts of my body.

I have a history of heart problems including a heart attack, heart failure, low heart pump function, irregular heartbeat, or significant valve issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HER2-targeted therapy with cardiac imaging every 3 months for standard care or every 4-6 months for judicious imaging based on risk

48 weeks

Imaging every 3 months (standard care) or every 4-6 months (judicious imaging)

Follow-up

Participants are monitored for heart health, treatment completion, and patient well-being after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intervention - Low Risk Group OR Intermediate Risk Group

Trial Overview The study is testing whether fewer heart tests are as safe and effective as the current standard of every three months. Low-risk patients will have tests every six months, while intermediate-risk ones will have them every four months. The outcomes on heart health, treatment completion, and patient satisfaction will be compared.

How Is the Trial Designed?

Group I: Judicious Imaging Experimental Treatment 1 Intervention

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.

Group II: Standard of Care Active Control 1 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.

Who Is Running the Clinical Trial?

Women's College Hospital

Lead Sponsor

Trials

108

Recruited

43,700+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

Citations

1. Spain pubmed.ncbi.nlm.nih.gov

Cardiotoxicity associated with trastuzumab in normal clinical practice. [2015]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Proteomics Analysis of Trastuzumab Toxicity in the H9c2 Cardiomyoblast Cell Line and its Inhibition by Carvedilol. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Cardiac assessment in Australian patients receiving (neo)adjuvant trastuzumab for HER2-positive early breast cancer: a population-based study. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Trastuzumab-related cardiotoxicity in early breast cancer: a cohort study. [2021]

5. France pubmed.ncbi.nlm.nih.gov

Potential impact of cardiac dose-volume on acute cardiac toxicity following concurrent trastuzumab and radiotherapy. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. [2022]

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

Trastuzumab for HER2+ metastatic breast cancer in clinical practice: Cardiotoxicity and overall survival. [2016]