Clinical trial NCT03908528: Alpha-Lipoic Acid in Breast Cancer Patients
Official title: Role of Alpha-Lipoic Acid Against Chemotherapy Induced Toxicities in Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Chemotherapeutic Toxicity
Keywords: alpha-lipoic acid
taxol
Adriamycin
cyclophosphamide
breast cancer
Brain Natriuretic Peptide (BNP).
Neurotensin
TNF-alpha
Lead sponsor: Damanhour University
Sponsor class: OTHER
First posted: 2019-04-09
Enrollment: 64
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: Double-blind study, Patients will be classified as follow:

* Group one: 32 patients will receive four cycles of AC followed by weekly taxol for 12 weeks plus placebo.
* Group two: 32 patients will receive four cycles of AC followed by weekly taxol for 12 weeks plus oral 600 mg alpha lipoic acid (ALA) once daily.
Primary purpose: TREATMENT

Brief summary: • Investigate the ability of alpha lipoic acid to counter act anthracycline associated cardiotoxicity and cumulative taxens-related PN in patients with breast cancer.

Detailed description: Fifty breast cancer patients with stage from stage I to stage III will be involved in this study. Staging is done according to the American joint committee on cancer: TNM staging of breast cancer.

* All participants will be recruited from Tanta Oncology Center. The study will be approved by Research Ethics Committee of Damanhour University. All participants will give their consent.
* All 64 patients will be scheduled to receive 4 cycles of AC: cycled every 21 days followed by weekly cycle of taxol for 12 weeks.

Patients will be classified as follow:

* Group one: 32 patients will receive four cycles of AC followed by weekly taxol for 12 weeks plus placebo.
* Group two: 32 patients will receive the same regimen as group 1 in addition to oral 600 mg alpha lipoic acid (ALA) once daily.

All patients will be submitted to:

1. Full patient history and clinical examination.
2. Venous blood will be collected before the first cycle of chemotherapy and after the last cycle of chemotherapy.

1- Cardio-toxcity assessment: i. Echo-cardiogram. ii. Troponin I. iii. The Brain Natriuretic Peptide (BNP). 2- Neurotoxicity assessment: i. National Cancer Institute common Terminology criteria for Adverse Effect grading: NCI-CTCAE version 4.0.

ii. Neurotoxicity questionnaire from the validated Functional Assessment of cancer therapy/gynecologic oncology group taxane specific neurotoxicity questionnaire: FACT-Taxane.

iii. Neurotensin 3- Oxidative stress and inflammatory markers: i. Malondialdehyde (MDA). ii. TNF-alpha

Eligibility criteria: Inclusion Criteria:

1. All patients age ≥ 18 and \< 70 years old with confirmed stage from stage I to stage III.
2. No evidence of metastases at initial assessment.
3. Patients has to have a good performance status (ECOG 0-2) according to Eastern Cooperative Oncology Group (ECOG) score.
4. Adequate baseline hematologic values (absolute neutrophilic count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin level ≥ 10g/dL).
5. Patients with adequate liver function (serum creatinine \< 1.5 mg/dL) and adequate renal function (serum creatinine \< 1.5 mg/dL, creatinine clearance (CrCl) \> 45 ml/min).
6. Either pre operative or post operative chemotherapy are allowed.

Exclusion Criteria:

1. Evidence of metastases at initial assessment.
2. Pregnancy or breast-feeding patients.
3. Prior exposure to neurotoxic chemotherapy was not allowed (no carboplatin, vincristine, vinblastine, paclitaxel, or docetaxol ) for 6 months prior study treatment.
4. Clinical evidence of serious cardiac illness (myocardial dysfunctional, angina pectoris requiring anti-angina medication, poorly controlled hypertension, and uncontrolled arrhythmias).
5. Patients with a reduced cardiac output with a left ventricular ejection fraction (LVEF) ejection fraction \< 50%.
6. Patients who had evidence of pre-existing peripheral neuropathy resulting from another reason (diabetes).
7. Patients with a history of allergy to alpha-lipoic acid.
8. Concomitant use of multivitamins (vitamin E), opioids, anticonvulsants, tricyclic antidepressants, other neuropathic pain medication modifying agents (e.g., gabapentin, lamotrigine, carbamazepine, phenytoin, or tricyclic antidepressants) are not allowed

Primary outcomes:
measure: Cardiotoxcity assessment
timeFrame: six months
measure: Neurotoxicity assessment
timeFrame: six months
measure: oxidative stress and inflammatory markers
timeFrame: six months
measure: MDA
timeFrame: six months
Secondary outcomes:
Other outcomes:
Locations:
city: Tanta
country: Egypt
facility: Tanta Oncology Center
state: Gharbia
Study officials:
affiliation: Damanhour University
name: Reham A Elshafiey, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kapoor S. The Anti-neoplastic Effects of Alpha-Lipoic Acid: Clinical Benefits in System Tumors besides Lung Carcinomas. Korean J Thorac Cardiovasc Surg. 2013 Apr;46(2):162-3. doi: 10.5090/kjtcs.2013.46.2.162. Epub 2013 Apr 9. No abstract available.
citation: Werida RH, Elshafiey RA, Ghoneim A, Elzawawy S, Mostafa TM. Role of alpha-lipoic acid in counteracting paclitaxel- and doxorubicin-induced toxicities: a randomized controlled trial in breast cancer patients. Support Care Cancer. 2022 Sep;30(9):7281-7292. doi: 10.1007/s00520-022-07124-0. Epub 2022 May 21.