The Effect of Metformin on Breast Cancer Patients

Study Overview
=================
Brief Summary
-----------------
Several clinical trials have addressed the promising anticancer effect of metformin on the survival benefits, clinical response, and pathological response of breast cancer patients. Therefore, this study will assess the anticancer effect of metformin when added to the neoadjuvant chemotherapy protocol of non-diabetic breast cancer patients. In addition to, the impact of metformin addition to the neoadjuvant chemotherapy on the quality of life of breast cancer patients.

Detailed Description
-----------------
This study is conducted to assess the effect of metformin addition to the chemotherapy protocol of non-diabetic breast cancer patients compared to the control group (non-metformin users) in the neoadjuvant setting. Evaluation of the the clinical benefit rate and the rate of pathological complete response will be conducted. In addition, a correlation between the beneficial effect of metformin and the serum concentration of metformin. Also, a comparison in the quality of life between the metformin group and the control group will be evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) and (EORTC QLQ BR45) questionnaires will be done.

Official Title
-----------------
The Effect of Metformin on Breast Cancer Patients

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: Metformin
* Drug: Chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Non-diabetic breast cancer patients, receiving neoadjuvant chemotherapy treatment. Female Age between 18- 65 years. Written informed consent. Exclusion Criteria: Known hypersensitivity reaction to Metformin. Intolerable Metformin GI complaints. Patients at risk of lactic acidosis. Diabetic breast cancer patients. Body Mass Index < 18.5 (underweight breast cancer patients). Renal impairment, eGFR <45 mL/min/1.73 m².

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study is an open-labeled, parallel, randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: metformin arm<br>4 cycles (Doxorubicin+Cyclophosphamide) followed by 12 cycles Paclitaxel+ Metformin (1000 mg twice daily) followed by surgery. | Drug: Metformin<br>* first-line anti-diabetic drug<br>* Other names: Glucophage;Drug: Chemotherapy<br>* First line neoadjuvant chemotherapy protocol<br>* Other names: Paclitaxel;|
| Active Comparator: control arm<br>4 cycles (Doxorubicin+Cyclophosphamide) followed by 12 cycles Paclitaxel followed by surgery. | Drug: Chemotherapy<br>* First line neoadjuvant chemotherapy protocol<br>* Other names: Paclitaxel;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit rate (Tumor size) | Tumor size measured in calipers from baseline till the last cycle of neoadjuvant chemotherapy. | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response | The absence of residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy. | 8 months | 
| Number of participants with metformin-related adverse events | Safety and tolerability of conventional anti-diabetic dose of metformin use in breast cancer patients. | 8 months | 
| The effect of metformin on the quality of life of breast cancer patients | A comparison between the metformin arm and the control arm in the change of quality of life from baseline using the European Organization for Research and Treatment of Cancer (EORTC QLQ C30 tools. Scoring of the EORTC QLQ-C30 is performed according to the EORTC scoring manual. After the scoring procedures, all the responses to likert-scale items were linearly transformed to a 0-100 scale. Higher scores for functional scales and the global quality of life scale, indicate better quality of life, while for symptom scales and single items, a higher score indicates a higher severity of the symptoms and worse quality of life. | 8 months | 
| The effect of metformin on the quality of life of breast cancer patients | A comparison between the metformin arm and the control arm in the change of quality of life from baseline using the European Organization for Research and Treatment of Cancer (EORTC QLQ BR45).Scoring of the EORTC QLQ-Br45 is performed according to the EORTC scoring manual. After the scoring procedures, all the responses to likert-scale items were linearly transformed to a 0-100 scale. Higher scores for functional scales and the global quality of life scale, indicate better quality of life, while for symptom scales and single items, a higher score indicates a higher severity of the symptoms and worse quality of life | 8 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metformin, Breast cancer