Role of Adding Metformin to Neoadjuvant Chemotherapy in Patients With Breast Cancer (METNEO)
Condition: Breast Cancer Female
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Metformin Hydrochloride 850 mg Tablets; AC-T chemotherapy regimen
Intervention type(s): Drug; Drug
Intervention description(s): Oral administration of Metformin hydrochloride 850 mg tablets (1700 mg/day) daily until the completion of neoadjuvant chemotherapy cycles; AC: (Doxorubicin 60 mg/m2 IV + cyclophosphamide 600 mg/m2 IV) for 4 cycles every 3 weeks followed by Taxol cycles (Paclitaxel 80 mg/m2 IV) once weekly for 12 weeks.
Other intervention name(s): Cidophage 850 mg; AC (doxorubicin [Adriamycin] + cyclophosphamide) followed by paclitaxel (Taxol)
Intervention MeSH terms: Metformin; Paclitaxel; Cyclophosphamide; Doxorubicin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized Controlled Trial
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Metformin; locally advanced breast cancer; neoadjuvant