Evaluation of Possible Safety and Efficacy of Fenofibrate in the Prophylaxis of Doxorubicin Induced Cardiotoxicity in Breast Cancer Patients

August 14, 2025 updated by: Hagar Khaled Bassuony Dewidar, Tanta University

Clinical Study to Evaluate the Possible Safety and Efficacy of Fenofibrate in the Prophylaxis of Doxorubicin Induced Cardiotoxicity in Breast Cancer Patients

This study aims at evaluating the possible safety and efficacy of fenofibrate in attenuating doxorubicin related cardiac toxicity in breast cancer patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Breast cancer represents the most frequently diagnosed malignancy and the second most common cause of cancer death worldwide (Sung et al., 2021). In Egypt, breast cancer is the most common malignancy in women, accounting for 38.8% of cancers in this population, with the estimated number of breast cancer cases nearly 22,700 in 2020 and forecasted to be approximately 46,000 in 2050 (Ibrahim et al., 2014).

Doxorubicin (DOX) is a cytotoxic agent that is commonly used for treatment of breast cancer. Despite its effectiveness, doxorubicin is associated with cumulative and potential cardiotoxicity (Rawat et al.,2021).

Although the precise mechanisms whereby DOX induces myocardial injury have not been fully elucidated, it is widely accepted that DOX induces cardiac injury via several mechanisms, including activation of nuclear factor- Kabba B (NF-ĸB), the induction of pro-inflammatory cytokines, the generation of free radicals, the promotion of apoptotic cell death, and the suppression of Endothelial progenitor cells (EPC) mobilization and function, which are typical changes observed in DOX-induced cardiotoxcity (Cardinale et al., 2020).

Peroxisome proliferator-activated receptor-α (PPARα) has been proposed as a key lipid metabolism modulator and regulator of inflammation. There are three isotypes of PPAR (α, β and ȣ) which have distinct but overlapping functions. Fenofibrate, an important PPAR- α agonist, is widely used in in the treatment for hypercholesterolemia and hypertriglyceridemia (Kim and Kim, 2020). Many studies demonstrated the pleiotropic effects of fenofibrate on the heart that afford direct myocardial protection in addition to the lipid-lowering effects through improvement of vascular endothelial function, reducing oxidative stress and increasing endothelial nitric oxide synthase (eNOS) activation (Walker et al., 2012; Jen et al., 2016).

In addition recent animal study showed that fenofibrate decreased the transactivation of Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activated endothelial nitric oxide synthase (eNOS) and increased nitric oxide (NO) bioavailability, which in turn suppressed MMP-2 (matrix 4 metalloproteinase-2) and MMP-9 (matrix metalloproteinase-9), a well-recognized mediator of adverse ventricular fibrosis and subsequent remodeling, which established the role of fenofibrate against DOX-induced cardiotoxicity in mice (Huang et al., 2021). In addition, it is known that DOX- increases circulating N-terminal pro-B-type natriuretic peptide (NT- pro-BNP) and B-type natriuretic peptide (BNP) that were attenuated by fenofibrate (Huang et al., 2021)

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
    • Elgharbya
      • Tanta, Elgharbya, Egypt, 31527
        • Hagar Dewidar

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years old.
  • Patients with biopsy confirmed diagnosis breast cancer and with stage II and stage III breast cancer according to the American Joint Committee on Cancer (TNM staging system of breast cancer).
  • Patients with performance status <2 according to Eastern Cooperative Oncology Group (ECOG) score.
  • Adequate baseline hematologic values (absolute neutrophilic count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L and hemoglobin level ≥ 10 g/dl).
  • Patients with adequate liver function (serum bilirubin < 1.2 mg/dl) and adequate renal function (serum creatinine < 1.5 mg/d).

Exclusion Criteria:

  • Patients with prior exposure to anthracyclines in the last 6 months.
  • Patients with evidence of metastasis at the initial assessment.
  • Concomitant use of antioxidant vitamins (vitamin A, C, E).
  • Presence of clinical evidence for severe cardiac illness (angina pectoris, uncontrolled hypertension, arrhythmias and left ventricular ejection fraction <50%).
  • Patients with inflammatory diseases (ulcerative colitis, rheumatoid arthritis).
  • Patients with conditions associated with oxidative stress (smoking, tuberculosis, comorbid obesity).
  • Patients who are candidates for monoclonal antibodies such as Trastuzumab and other targeted therapy (HER2 positive patients).
  • Patients with active liver disease (cirrhosis, fatty liver, hepatitis C, etc..).
  • Patients with myopathy.
  • Patients with renal impairment, including those with end-stage renal disease and those receiving dialysis.
  • Pregnant and breast feeding women.
  • Known allergy to the fenofibrates.
  • Concurrent use of statin, colchicine, ciprofibrate, idelalisib, ivacaftor, aspirin low strength, clopidogrel, warfarin, enzyme inducers (phenytoin, phenobarbitone, carbamazepine,…), enzyme inhibitors (allopurinol, MAOI, SSRI,…), drugs with high plasma protein binding capacity (sulfonamides, valproate, oral hypoglycemic, warfarin,…) in order to avoid potential pharmacodynamics and pharmacokinetic drug interactions.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo group
22 patients which will receive four cycles of AC regimen (doxorubicin and cyclophosphamide; each cycle is given every 21 day) plus placebo tablets once daily.
Other: Placebo
Placebo is made to look exactly like a real drug but is made of an inactive substance.
Drug: Doxorubicin
Anthracycline derived chemotherapy used in treatment of breast cancer
Drug: Cyclophosphamide
Alkylating agent used in treatment of breast cancer
Active Comparator: Fenofibrate group
22 patients which will receive four cycles of AC regimen (doxorubicin and cyclophosphamide; each cycle is given every 21 day) plus Fenofibrate 160 mg once daily.
Drug: Doxorubicin
Anthracycline derived chemotherapy used in treatment of breast cancer
Drug: Cyclophosphamide
Alkylating agent used in treatment of breast cancer
Drug: Fenofibrate
It is an approved drug for hypercholesterolemia, It lowers lipid levels by activating peroxisome proliferator-activated receptor alpha (PPARα).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of changes in ejection fraction (the amount of blood that heart pumps each beat) using echocardiography
Time Frame: 3 months
The primary outcome is to avoid decrease in patients ejection fraction while administrating doxorubicin which is known to cause a declination in cardiac ejection fraction threatening of heart failure
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in serum levels of the measured biological markers
Time Frame: 3 months
The secondary outcome is decrease in serum levels of the measured biological markers which are brain naturetic peptide and myeloperoxidase
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tanta University

Investigators

  • Principal Investigator: Hagar Dewidar, Instructor, Tanta university

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2023

Primary Completion (Actual)

January 1, 2025

Study Completion (Actual)

January 1, 2025

Study Registration Dates

First Submitted

November 19, 2023

First Submitted That Met QC Criteria

November 24, 2023

First Posted (Actual)

December 4, 2023

Study Record Updates

Last Update Posted (Actual)

August 19, 2025

Last Update Submitted That Met QC Criteria

August 14, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Breast cancer and fenofibrate

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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