A Prospective Study of Breast Cancer Patients With Abnormal Strain Imaging

NCT02993198 | Active Not Recruiting Phase 2

• 1 other identifier: STU00200675
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 1

Brief Summary

The Cardio-Oncology program at Northwestern offers care to cancer patients who develop cardiac toxicities from chemotherapy. Breast cancer patients with the tumor marker for HER2 necessitate treatment with anthracycline and/or trastuzumab and pertuzumab-based chemotherapies, which are known to cause cardiac toxicities. Breast cancer patients will undergo a "cardio-oncology echocardiogram" which incorporates advanced left ventricular assessment by utilizing deformation or strain imaging during chemotherapy treatment for surveillance of cardiac toxicities. The aims of this project are:

1. 1.To create a registry of both clinical, and echocardiographic variables, biomarkers, and genetic analysis that will be used to develop a risk model to predict LV dysfunction in early stage breast cancer patients undergoing chemotherapy with anthracycline and/or trastuzumab and pertuzumab-based chemotherapy regimens.
2. 2.To propose a new management algorithm for initiation of prophylactic beta-blocker therapy for early stage breast cancer patients with preclinical cardiac toxicities demonstrated by strain parameters.
3. 3.To determine if initiation of prophylactic beta-blocker therapy in patients with early cardiac toxicity can delay or prevent a drop in LV EF and the development of clinical heart failure.
4. 4.To explore serial measurements of a suite of novel biomarkers during ongoing anticancer treatment that are presumed but not yet proven to be predictive of cardiac dysfunction in women with breast cancer.
5. 5.To identify DNA biomarkers of predilection to cardiotoxicity.
6. 6.To generate hiPSC to validate markers predictive of cardiotoxicity.

Conditions

HER2 Positive Breast Cancer; Cardiovascular Abnormalities

Outcome Measures

Primary Outcomes (1)

• Change in Global Longitudinal Strain

  Improvement or stability in strain from baseline (i.e., increase in strain or decrease by no more than 3%).

  1 year

Secondary Outcomes (1)

• Number of cancer treatments

  1 year

Study Arms (2)

Prophylactic Carvedilol

EXPERIMENTAL

Carvedilol 3.125 mg by mouth every 12 hours, titrated to a max dose of 25 mg by mouth every 12 hours, depending on blood pressure and heart rate, until completion of study.

Drug: Carvedilol

No Therapy

NO INTERVENTION

Standard of care monitoring without prophylactic treatment.

Interventions

Carvedilol DRUG

Prophylactic Carvedilol

Eligibility Criteria

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

You may qualify if:

• Patients \> 18 years of age with HER2-overexpressing early stage breast cancer (Stages I - III)
• Pathology report must include HER2 expression, estrogen and progesterone receptor status
• Normal LV function (EF \> 53%) on baseline echocardiogram
• NYHA functional class I-II (no symptoms, dyspnea with more than 2 blocks)
• Scheduled to receive treatment with anthracycline and/or trastuzumab and pertuzumab-based regimens
• Patients with a history of HTN, hyperlipidemia, diabetes, mild CAD, mild valvular disease are permitted
• Patients on concomitant cardiac medications other than beta-blockers (BB) or ace-inhibitors (ACE) therapy are permitted. Other non-cardiac medications are not prohibited.
• Women of childbearing potential and sexually active men and women should use effective contraception.
• Patients must have a signed informed consent prior to registration

You may not qualify if:

• LV dysfunction (EF \< 53%)
• New York Heart Association (NYHA) functional class III-IV (heart failure symptoms at less than 2 blocks to advanced symptoms at rest)
• a. NYHA Classification: I - No limitations to activity II - Slight limitation to ordinary activity, no symptoms at rest III - Marked limitation to less than ordinary activity, no symptoms at rest IV - Inability to carry out activity without symptoms, symptoms at rest
• Pre-existing cardiac disease (moderate-severe coronary artery disease, moderate-severe valvular heart disease, constrictive/restrictive cardiomyopathies)
• Metastatic breast cancer
• Patients who have ever taken BB/ACE therapy are excluded.
• nd and 3rd degree AV block
• Sick sinus syndrome
• Patients with severe bradycardia (\< 50 bpm) or severe hypotension (SBP \< 85 mmHg)
• Severe liver dysfunction defined as Child-Turcotte-Pugh class B \& C (significant functional compromise - decompensated disease)
• Moderate-severe Asthma
• Hypersensitivity to beta-blockers
• Patients who are pregnant/lactating are not eligible
• Unwilling to consent/assent to blood donation

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Related Publications (1)

• Gong FF, Grunblatt E, Voss WB, Rangarajan V, Raissi S, Chow K, Jafari L, Patel NP, Vaitenas I, Marion M, Ramirez H, Zhao M, Andrei AC, Baldridge AS, Murtagh G, Maganti K, Rigolin VH, Akhter N. A strain-guided trial of cardioprotection in early-stage breast cancer patients on anti-HER2 therapy (PROTECT HER2). Cardiooncology. 2024 Nov 27;10(1):85. doi: 10.1186/s40959-024-00291-5.

  PMID: 39605014 DERIVED

MeSH Terms

Conditions

Cardiovascular Abnormalities

Interventions

Carvedilol

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: December 15, 2016
• Study Start: April 1, 2015
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: June 3, 2024

Record last verified: 2024-05

Locations

US (1)