Clinical trial NCT04170465: Role of Adding Metformin to Neoadjuvant Chemotherapy in Patients With Breast Cancer (METNEO)
Official title: Investigation of the Potential Beneficial Effect of Adding Metformin to Neoadjuvant Chemotherapy in Patients With Breast Cancer (METNEO)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer Female
Keywords: Metformin
locally advanced breast cancer
neoadjuvant
Lead sponsor: Damanhour University
Sponsor class: OTHER
Collaborators: name: Alexandria University
First posted: 2019-11-20
Enrollment: 70
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Controlled Trial
Primary purpose: TREATMENT

Brief summary: Metformin, the widely prescribed oral hypoglycemic drug, is well known for its established efficacy, favorable safety profile, and low cost. Metformin has recently received increasing attention because of its potential antitumorigenic effects that are thought to be independent of its hypoglycemic effects. It has been extensively studied in preclinical models, which have implicated several molecular pathways in its antitumor activity.

Metformin was proved to have anti-proliferative and apoptotic effects on tumor cells.Moreover, metformin enhances the T-cell mediated immune response to tumor tissue and fights metastases. Also, epidemiological studies have shown that metformin, but not other antidiabetic drugs, reduces cancer incidence and improves survivability in diabetic cancer patients.

The proposed research in this application will investigate two prime questions with regards to the combined use of metformin together with traditional neoadjuvant chemotherapy in breast cancer patients. First, the hypothesis that the simultaneous use of metformin along with doxorubicin/cyclophosphamide/paclitaxel neoadjuvant protocol produces better antitumor outcomes will be tested. Second, the study will examine if the improved apoptotic effect of such regimen is paralleled by exaggerated stimulatory influences on apoptosis biomarkers.

Detailed description: 1. Ethical committee approval will be obtained from Ethics committee of Faculty of Pharmacy, Damanhour University.
2. All participants should agree to take part in this clinical study and will provide informed consent.
3. Sixty female breast cancer patients, who are candidates for neoadjuvant chemotherapy, will be recruited from the Medical Research Institute, Oncology department, Alexandria University, Alexandria.
4. The 60 participants will be randomly assigned into 2 arms:

   * Control arm (n=30): will be treated with AC-Taxol regimen (AC: Doxorubicin 60 mg/m2 IV + cyclophosphamide 600 mg/m2 IV) for 4 cycles every 3 weeks. Subsequent Taxol cycles (Paclitaxel 80mg/m2 IV) once weekly for 12 weeks.
   * Metformin arm (n=30): will be treated with the AC-Taxol regimen mentioned above together with Metformin 850 mg tablets orally twice per day (1700 mg/day).
5. All patients will be submitted to:

   * Full patient history and clinical examination.
   * Routine follow up before each chemotherapy cycle (complete blood picture, liver function tests, renal function tests).
   * Routine Echocardiography before each chemotherapy cycle.
6. All patients will be monitored for the incidence of chemotherapy toxicities during neoadjuvant therapy.
7. After completion of the neoadjuvant therapy, participants will undergo surgical tumor removal. The excised tumor will be collected, and the expression of apoptosis biomarkers and the pathologic complete response (pCR) will be assessed.
8. Patients demographic data will be recorded with respect to age, weight and disease history.
9. Statistical tests appropriate to the study design will be conducted to evaluate the significance of the results.
10. Results, conclusion, discussion and recommendations will be given.

Eligibility criteria: Inclusion Criteria:

1. Females ≥ 18 years of age and \< 65 years.
2. Unilateral or bilateral primary carcinoma of the breast confirmed.
3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2.
4. Clinically measurable tumor size who are candidates for neoadjuvant therapy.
5. No evidence of distant metastasis.
6. Normal renal and liver functions.
7. Non-diabetics.

Exclusion Criteria:

1. Pregnant or breastfeeding women.
2. Prior cancer chemotherapy.
3. Heart disease or reduced cardiac output with left ventricular ejection fraction \< 50%.
4. Metastatic breast cancer patients.
5. Patients with hepatic impairment.
6. Patients with renal impairment.
7. Diabetics.

Primary outcomes:
measure: Evaluation of the effect on tumor apoptosis
timeFrame: 6 months
measure: Chemotherapy toxicities
timeFrame: 6 months
Secondary outcomes:
measure: Pathologic complete response rate (pCR)
timeFrame: 6 months
Other outcomes:
Locations:
city: Beheira
country: Egypt
facility: Damanhour University
Study officials:
affiliation: Professor in Pharmacology, Faculty of Pharmacy, Alexandria University
name: Mahmoud M El-Mas, PhD
role: STUDY_DIRECTOR
affiliation: Professor in Clinical Oncology, Medical Research Institute,Alexandria University
name: Yasser M El-Kerm, PhD
role: STUDY_DIRECTOR
affiliation: Professor in Pharmacology, Faculty of pharmacy, Damanhour University
name: Maged W Helmy, PhD
role: STUDY_CHAIR
affiliation: Lecturer in Clinical Pharmacy, Faculty of Pharmacy, Damanhour University
name: Amira B Kassem, PhD
role: STUDY_CHAIR
affiliation: Lecturer in Clinical Pharmacy, Faculty of Pharmacy, Damanhour University
name: Noha A El-Bassiouny, PhD
role: STUDY_CHAIR
affiliation: Teaching assistant in Pharmacology, Faculty of Pharmacy, Alexandria University
name: Manar A Serageldin, Bachelor
role: PRINCIPAL_INVESTIGATOR
References: