Clinical trial NCT06703593: Prevention of Doxorubicin-induced Cardiotoxicity in Breast Cancer Patients
Official title: Evaluation of the Impact of Alpha Lipoic Acid Administration on the Prevention of Doxorubicin-induced Cardiotoxicity in Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Cancer Female
Keywords: Alpha lipoic acid, Anthracyclines induced Cardiotoxicity
Lead sponsor: British University In Egypt
Sponsor class: OTHER
Collaborators: name: Ain Shams University
First posted: 2024-11-25
Enrollment: 80
Sex: FEMALE
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: According to the European Society of Cardiology 2022, the primary prevention of cancer therapyrelated cardiovascular toxicity during anthracycline chemotherapy include renin-angiotensin- aldosterone system blockers, beta-blockers, and mineralocorticoid receptor antagonists that have shown a significant benefit in preventing left ventricular ejection fraction (LVEF) reduction, but with no statistical differences in the incidence on the various other clinical outcomes as overt congestive heart failure (CHF). Also, other strategies have been investigated including; adjusting the infusion time and dose intensity of anthracyclines. Dexrazoxane and liposomal anthracyclines are currently approved in patients with high and very high chemotherapy-related cardiovascular disease (CTRCD) risk or who have already received high cumulative anthracyclines doses (Lyon, 2022). The incidence is about 4% when the dose of doxorubicin is 500-550 mg/m2, 18% when the dose is 551-600 mg/m2 and 36% when the dose exceeds 600 mg/m2 (Lefrak, 1973). Alpha-lipoic acid (ALA) was reported to have a cardioprotective role against doxorubicin-induced cardiotoxicity through attenuation of oxidative stress via scavenging reactive oxygen species (ROS), regenerating endogenous antioxidants including glutathione, vitamin E, and C, its metal chelation activity and its ability to repair oxidative damage. (Werida et al, 2022)

Detailed description: ALA effectively inhibits nuclear factor-kappa B with subsequent decreasing pro- inflammatory cytokines production (TNF-α, IL-6) and increasing the release of anti- inflammatory cytokines such as interleukin-10 (FahimehHaghighatdoostabMitraHariri, 2019).

Relying on the antioxidant and anti-inflammatory effect of Alpha lipoic acid confirmed by a variety of studies in vitro and in vivo, ALA is selected to be studied in Egyptian breast cancer patients who will be treated with doxorubicin including regimens.

Aim of the study:

The aim of the current study is to evaluate the efficacy and tolerability of ALA administration and its impact on the occurrence of doxorubicin-induced cardiotoxicity in Egyptian women with breast cancer by evaluation of the following:

1. Evaluation of the occurrence of chemotherapy induced cardiotoxicity by;

   1. Changes in echocardiographic findings and serum levels of pro brain natriuretic peptide (pro-BNP) and cardiac troponins.
   2. Severity of DIC will be evaluated by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 For Heart Failure.
   3. Estimation of oxidative stress burden by measurement of MDA.
2. Evaluation of ALA safety by:

ALA safety will be monitored and assessed through patient face to face interviews (at the end of each cycle) and phone calls weekly about the occurrence of any of the following side effects: (Ex; insomnia, fatigue, diarrhea, and skin rash).

Patients will be followed up by monitoring of the side effect reporting card (intervention arm)

Eligibility criteria: Inclusion Criteria:

1. Women aged more than 18 years
2. Breast cancer diagnosis
3. Entering first cycle of chemotherapy containing ATC
4. Subject must be willing and able to sign an informed consent

Exclusion Criteria:

1. History of renal (serum creatinine greater than 2.0 mg/ml) or hepatic insufficiency (bilirubin\> 3.0 mg/dl or serum albumin \< 3.5 g/dl or prothrombin time \< 60% in the absence of orally administered anticoagulant therapy or ultrasound signs of chronic liver damage
2. History of heart failure
3. Baseline LVEF \< 50% determined by transthoracic echocardiogram
4. Current participation in any other clinical investigation
5. History of severe adverse reaction to Alpha lipoic acid
6. Concomitant use of Trastuzumab (HER2 positive patients)
7. Previous intake of alpha lipoic acid in the previous 3 months
8. Women with prior exposure to anthracyclines and neurotoxic agents (Cis-platin, vincristine, paclitaxel, docetaxel, foscarnet, isonicotinic acid hydrazide "INH,", etc.) in the last 6 months.
9. Presence of clinical evidence for severe cardiac illness (i.e., angina pectoris and arrhythmias)
10. Any condition that contraindicates chemotherapy (i.e., pregnancy, lactation)

Primary outcomes:
measure: Changes in echocardiographic findings
timeFrame: Approximately few days ( less than a week ) before Cycle 1 "baseline" and after Cycle 4 "End Cycle" of Doxorubicin. Each cycle is 21 days.
measure: Changes in serum levels of pro brain natriuretic peptide (pro-BNP) and cardiac troponins
timeFrame: Just before Cycle 1 "baseline" and 1 hour after Cycle 4 "End Cycle" of Doxorubicin. Each cycle is 21 days.
Secondary outcomes:
measure: Changes in the oxidative stress marker malondialdehyde (MDA)
timeFrame: ust before Cycle 1 "baseline" and 1 hour after Cycle 4 "End Cycle" of Doxorubicin. Each cycle is 21 days.
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: The British University in Egypt
state: El-Sherouk City
Study officials:
References: