Evaluation of the Cardioprotective Effect of Nebivolol on Trastuzumab-Induced Cardiotoxicity in Breast Cancer Patients

NCT07233499 | Recruiting Phase 2 DMC

• 2 other identifiers: PHCLMSC200NCI-323
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

Breast cancer can be managed using chemotherapy, endocrine therapy and biological therapy. Treatment is determined and specified according to the characteristics of the tumor including overexpression of the human epidermal growth factor receptor (HER2). Previously patients who were diagnosed with HER2 positive breast cancer were considered of poor survival but after the discovery of trastuzumab, disease free survival among these patients was improved significantly. Though trastuzumab has made great improvement in the treatment of breast cancer, it was identified to possess a major side effect which is cardiotoxicity . Cardiotoxicity that occurs with anticancer agents is usually manifested as left ventricular dysfunction (LVD) and overt heart failure (HF). LVD was defined as a decrease in cardiac LV ejection fraction (LVEF), that is either global or more severe in the septum, symptoms of congestive heart failure (CHF), associated signs of CHF including but not limited to S3 gallop, tachycardia or both and decline in LVEF of at least 5% to below 55% with accompanying signs or symptoms of CHF, or a decline in LVEF of at least 10% to below 55% without accompanying signs or symptoms. Beta blockers have shown a cardioprotective effect against chemotherapy induced- cardiotoxicity. Nebivolol is a third-generation beta blocker. It is highly selective to B1- adrenergic receptors. It also has peripheral vasodilating effect due to its effect on L-arginine/ nitric oxide pathway in the endothelium of blood vessels. The dose of nebivolol given in the study was 5mg/day for the entire period of the study. Echo was done for all patients to determine the changes of left ventricular ejection fraction in patients in the treatment group and control group. The study concluded that nebivolol prevented the occurrence of anthracycline induced cardiotoxicity. the current study will be the first clinical trial to evaluate the cardioprotective effect of nebivolol on trastuzumab-induced cardiotoxicity in breast cancer patients. Aim of the work Evaluation of the effect of Nebivolol on trastuzumab - induced cardiotoxicity in non-metastatic breast cancer patients by assessment of:

• Left ventricular ejection fraction.
• Cardiac biomarkers (troponin- Pro- BNP).
• Treatment safety.
• Patient quality of life (Using fact-B questionnaire)

Conditions

HER2-positive Breast Cancer

Keywords

Breast cancer; Nebivolol; trastuzumab; HER-2 positive

Outcome Measures

Primary Outcomes (1)

• Measurement of Left ventricular ejection fraction by Echocardiography

  Echo will be done at baseline (before start of trastuzumab) and every 3 months during receiving trastuzumab to evaluate the reduction in the left ventricular ejection fraction and overall cardiac function

  12 months

Secondary Outcomes (3)

• II-Evaluation of cardiac biomarkers.

  12 months

• Number of participants with treatment-related adverse events

  12 months.

• Evaluation of Quality of Life.

  12 months

Study Arms (2)

Nebivolol

EXPERIMENTAL

Nebivolol group (28 patients): will receive nebivolol at a dose of 5 mg once daily (orally) during the whole period of receiving trastuzumab

Drug: Nebivolol 5 mg

Control group

NO INTERVENTION

Control group (28 patients): will receive no intervention during the trastuzumab therapy

Interventions

Nebivolol 5 mg DRUG

nebivolol tablet 5 mg once daily

Nebivolol

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old.
• Newly diagnosed with early or locally advanced HER2 positive breast cancer.
• Normal baseline LVEF (˃50%)
• Planned to receive HER2-directed therapies as newadjuvant or adjuvant.

You may not qualify if:

• Elderly patients( ˃65 years).
• Primary tumors other than breast cancer.
• Pregnancy and breast feeding.
• Currently using cardioprotective drugs e.g.: ACEI, CCB, ARBs and another beta blocker.
• Presence of diagnosed cardiomyopathy currently or in initial evaluation.
• Patients with ischemic heart disease.
• Contraindication for treatment with beta blockers.
• Patients with hypersensitivity to nebivolol.
• Poorly echogenic patients.

Sponsors & Collaborators

• Ain Shams University: lead
• National Cancer Institute, Egypt: collaborator

Study Sites (1)

National Cancer Institute- Cairo University- Egypt

Cairo, Egypt

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Nebivolol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

May A Shawki, Ph.D

CONTACT

01001701461; mayahmed@pharma.asu.edu.eg

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: Associate professor

Model Details: prospective randomized controlled study

Study Record Dates

• First Submitted: November 6, 2025
• First Posted: November 18, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)