Clinical trial NCT05959889: Effect of Montelukast on Doxorubicin Induced Cardiotoxicity in Breast Cancer
Official title: Evaluating the Effect of Montelukast on Doxorubicin Induced Cardiotoxicity in Breast Cancer Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Doxorubicin Induced Cardiotoxicity
Keywords: Montelukast
Doxorubicin
Induced Cardiotoxicity
Breast cancer Patients
Lead sponsor: Damanhour University
Sponsor class: OTHER
First posted: 2023-07-25
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: a prospective, randomized (1:1) controlled trial that will be carried out on 50 patients who are candidate to evaluate the effect of montelukast on doxorubicin induced cardiotoxicity after 4 cycles of AC. Patients will be randomly allocated into two equal groups (25 patients each); group (A) for controlled (placebo), and group (B) for montelukast
Primary purpose: TREATMENT

Brief summary: This is a prospective, randomized (1:1) controlled trial that will be carried out on 50 patients who are candidate to evaluate the effect of montelukast on doxorubicin induced cardiotoxicity after 4 cycles of AC. Patients will be randomly allocated into two equal groups (25 patients each); group (A) for controlled (placebo), and group (B) for montelukast. Blood samples will be collected from the study subjects and analyzed for serum levels of the NF-KB and pro-BNP. Assessment of the biomarkers will be done at two time points: at baseline and after treatment with montelukast.

Detailed description: The primary objective of this study is to evaluate the effect of montelukast on doxorubicin induced cardiotoxicity in breast cancer patients through assessing serum NT-proBNP and NF-KB. The secondary objective is to evaluate the safety and side effects of montelukast on doxorubicin induced cardiotoxicity in breast cancer patients.

Methodology and study design:

1. Ethical committee approval will be obtained from Ethics committee of Faculty of Pharmacy, Damanhour University.
2. About 50 patients who are candidate to the study will be recruited from Damanhour Cancer Institute.
3. All participants will provide an informed consent.
4. Demographic data; age (year), sex (female/male), weight (kg), height (cm), BMI (kg/m2) will be collected.
5. About 5 ml of venous blood will be withdrawn by antecubital venipuncture from each participant at baseline and after receiving montelukast 10 mg once daily at bed time for 4 cycles of AC. At each time point blood samples will be collected into plain test tubes and centrifuged at 4500×g for 10 min and serum will be frozen at - 80 ◦C until analysis of the biomarkers using ELISA kits.
6. Montelukast tablets will be provided on monthly intervals and the participants' adherence will be assessed through the medications refilling rate. Participants will also be followed-up by weekly telephone calls and monthly direct meetings to assess their adherence and report any drug related adverse effects.

Eligibility criteria: Inclusion Criteria:

1. Adult patients (age≥18 and≤ 70years old) with biopsy-confirmed diagnosis of breast cancer according to the American Joint Committee on Cancer (TNM staging system).
2. Patients with performance status (\<2) according to Eastern Cooperative Oncology Group (ECOG).
3. Patients with adequate hematologic parameters (absolute neutrophil count≥1.5× 109/L, platelet count≥100× 109/L, hemoglobin level≥10 g/dl), adequate liver function (serum bilirubin\<1.5 mg/dl), and adequate renal function (serum creatinine\<1.5 mg/dl, creatinine clearance (CrCl)\>45 ml/min).

Exclusion Criteria:

1. Patients who refuse to sign the written consent.
2. If blood cell counts are too low.
3. Severe liver problem.
4. Recent heart attack or have severe heart problems.
5. Previous treatment with Doxorubicin or certain other anticancer medications.
6. Allergy to certain other anti-cancer medicines, doxorubicin hydrochloride, Cis-platin, vincristine, paclitaxel, docetaxel, foscarnet, etc.

   in the last 6 months.
7. Women with evidence of metastasis at the initial assessment.
8. Presence of clinical evidence for severe cardiac illness (angina pectoris, uncontrolled hypertension, arrhythmias, and left ventricular ejection fraction\<50%).
9. Pregnant and breast-feeding women.

Primary outcomes:
measure: NF-KB
timeFrame: 6 months
measure: pro-BNP
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Damanhūr
country: Egypt
facility: Damanhour Oncology Center
state: Elbehairah
Study officials:
affiliation: Damanhour University
name: Noha A. El bassiouny, Lecturer
role: STUDY_DIRECTOR
References:
citation: Said MM, Bosland MC. The anti-inflammatory effect of montelukast, a cysteinyl leukotriene receptor-1 antagonist, against estradiol-induced nonbacterial inflammation in the rat prostate. Naunyn Schmiedebergs Arch Pharmacol. 2017 Feb;390(2):197-205. doi: 10.1007/s00210-016-1325-4. Epub 2016 Dec 1.
citation: Elnoury HA, Elgendy SA, Baloza SH, Ghamry HI, Soliman M, Abdel-Aziz EA. Synergistic impacts of Montelukast and Klotho against doxorubicin-induced cardiac toxicity in Rats. Toxicol Res (Camb). 2022 Jun 20;11(4):592-604. doi: 10.1093/toxres/tfac023. eCollection 2022 Aug.