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

NCT06155331 | Completed Phase 2

• 1 other identifier: Breast cancer and fenofibrate
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Breast Cancer Stage 2 and 3

Keywords

Breast cancer , Doxorubicin, Fenofibrate , Cardiotoxicity

Outcome Measures

Primary Outcomes (1)

• Assessment of changes in ejection fraction (the amount of blood that heart pumps each beat) using echocardiography

  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 Outcomes (1)

• Changes in serum levels of the measured biological markers

  3 months

Study Arms (2)

Placebo group

PLACEBO COMPARATOR

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; Drug: Doxorubicin; Drug: Cyclophosphamide

Fenofibrate group

ACTIVE COMPARATOR

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: Fenofibrate; Drug: Doxorubicin; Drug: Cyclophosphamide

Interventions

Fenofibrate DRUG

It is an approved drug for hypercholesterolemia, It lowers lipid levels by activating peroxisome proliferator-activated receptor alpha (PPARα).

Fenofibrate group

Placebo OTHER

Placebo is made to look exactly like a real drug but is made of an inactive substance.

Placebo group

Doxorubicin DRUG

Anthracycline derived chemotherapy used in treatment of breast cancer

Fenofibrate group; Placebo group

Cyclophosphamide DRUG

Alkylating agent used in treatment of breast cancer

Fenofibrate group; Placebo group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

Hagar Dewidar

Tanta, Elgharbya, 31527, Egypt

Location

Related Publications (11)

• Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017 Mar;67(2):93-99. doi: 10.3322/caac.21388. Epub 2017 Jan 17.

  PMID: 28094848 BACKGROUND

• Cardinale D, Iacopo F, Cipolla CM. Cardiotoxicity of Anthracyclines. Front Cardiovasc Med. 2020 Mar 18;7:26. doi: 10.3389/fcvm.2020.00026. eCollection 2020.

  PMID: 32258060 BACKGROUND

• Czupryniak L, Joshi SR, Gogtay JA, Lopez M. Effect of micronized fenofibrate on microvascular complications of type 2 diabetes: a systematic review. Expert Opin Pharmacother. 2016 Aug;17(11):1463-73. doi: 10.1080/14656566.2016.1195811. Epub 2016 Jun 15.

  PMID: 27267786 BACKGROUND

• Huang WP, Yin WH, Chen JS, Huang PH, Chen JW, Lin SJ. Fenofibrate attenuates doxorubicin-induced cardiac dysfunction in mice via activating the eNOS/EPC pathway. Sci Rep. 2021 Jan 13;11(1):1159. doi: 10.1038/s41598-021-80984-4.

  PMID: 33441969 BACKGROUND

• Ibrahim AS, Khaled HM, Mikhail NN, Baraka H, Kamel H. Cancer incidence in egypt: results of the national population-based cancer registry program. J Cancer Epidemiol. 2014;2014:437971. doi: 10.1155/2014/437971. Epub 2014 Sep 21.

  PMID: 25328522 BACKGROUND

• Jen HL, Liu PL, Chen YH, Yin WH, Chen JW, Lin SJ. Peroxisome Proliferator-Activated Receptor alpha Reduces Endothelin-1-Caused Cardiomyocyte Hypertrophy by Inhibiting Nuclear Factor-kappaB and Adiponectin. Mediators Inflamm. 2016;2016:5609121. doi: 10.1155/2016/5609121. Epub 2016 Oct 11.

  PMID: 27807394 BACKGROUND

• Kim NH, Kim SG. Fibrates Revisited: Potential Role in Cardiovascular Risk Reduction. Diabetes Metab J. 2020 Apr;44(2):213-221. doi: 10.4093/dmj.2020.0001.

  PMID: 32347023 BACKGROUND

• Rawat PS, Jaiswal A, Khurana A, Bhatti JS, Navik U. Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management. Biomed Pharmacother. 2021 Jul;139:111708. doi: 10.1016/j.biopha.2021.111708. Epub 2021 May 13.

  PMID: 34243633 BACKGROUND

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

• Walker AE, Kaplon RE, Lucking SM, Russell-Nowlan MJ, Eckel RH, Seals DR. Fenofibrate improves vascular endothelial function by reducing oxidative stress while increasing endothelial nitric oxide synthase in healthy normolipidemic older adults. Hypertension. 2012 Dec;60(6):1517-23. doi: 10.1161/HYPERTENSIONAHA.112.203661. Epub 2012 Oct 29.

  PMID: 23108655 BACKGROUND

• Dewidar HK, Ghannam AA, Mostafa TM. Fenofibrate attenuates doxorubicin-induced cardiotoxicity in patients with breast cancer: a randomized controlled trial. Naunyn Schmiedebergs Arch Pharmacol. 2025 Dec;398(12):17109-17119. doi: 10.1007/s00210-025-04326-1. Epub 2025 Jun 3.

  PMID: 40459761 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Cardiotoxicity

Interventions

Fenofibrate; Doxorubicin; Cyclophosphamide

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

Intervention Hierarchy (Ancestors)

Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Phenyl Ethers; Ethers; Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols; Ketones; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Hagar Dewidar, Instructor

  Tanta University

  PRINCIPAL INVESTIGATOR

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: Instructor of clinical pharmacy

Study Record Dates

• First Submitted: November 19, 2023
• First Posted: December 4, 2023
• Study Start: December 1, 2023
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: August 19, 2025

Record last verified: 2025-08

Locations

EG (1)