Metformin Plus Neoadjuvant Chemotherapy in Breast Cancer

Study Overview
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Brief Summary
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Background Obesity and overweight are well known risk factors for breast cancer and also are associated with higher recurrence and mortality rates. Main goal of this study is to evaluate the efficacy of metformin plus chemotherapy in terms of pathologic complete response in comparison with placebo plus the same chemotherapy regimen Design: Randomized, double blind, clinical trial. This study will be performed at National Cancer Institute of Mexico City, at breast cancer unit. Patients with ER+ or PR+, HER2 negative, breast cancer are candidates to participate. After completion of chemotherapy all patients will have a breast surgery to assess pathologic response. Complete pathologic response is defined as the abscence of malignant cells in breast tissue and lymph nodes. The presence of DCIS is considered as pCR

Detailed Description
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Definitions Luminal A: tumors ER + PR + HER2 Negative and Ki67 <14% Luminal B: tumors ER +/-, PR +/-, HER2 negative and Ki67 >15% Complete pathologic response is defined as the abscence of malignant cells in breast tissue and lymph nodes. The presence of DCIS is considered as pCR

Official Title
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Clinical Phase II, Randomized, Double Blind Trial, to Evaluate the Efficacy of Metformin and Chemotherapy Versus Placebo Nad Chemotherapy in Neoadjuvant Setting for Locally Advanced Breast Cancer

Conditions
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Locally Advanced Malignant Neoplasm

Intervention / Treatment
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* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women older than 18 years old and younger than 70 years old Invasive breast cancer confirmed by core biopsy, any histology Tumor ≥2 cm and/or lymph node positive (proven by FNA)(T2-4b, N0-3, M0) Must have ER/PR positive and HER2 negative Must have full staging and extent disease and clinically and radiographically tumor measure Without previous treatment for breast cancer (including surgery, hormonotherapy or chemotherapy) Normal liver, kidney and blood tests Performance Status ECOG 0-2 o Karnofsky ≥70% Fasten glucose levels <125 mg/dl Signed consent Exclusion Criteria: Previous use of metformin for any indication Presence of Diabetes Mellitus

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>Patients will be receive 12 weeks of paclitaxel followed by 4 cycles of FAC combined with 500 mg/day of metformin p.o. | Drug: Metformin<br>* metformin 500 mg/day po for 24 weeks.<br>* Other names: Dabex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathologic complete response | to assess the efficacy in terms of pahtologic complete response in patients with locally advanced breast cancer, treated with neoadjuvant chemotherapy based on Paclitaxel followed by FAC, combined with metformin or placebo | pCR will be assesed after 24 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety analysis | For safety analysis we are going to use NCTC criteria version 3.0 | after 24 treatment weeks' | 
| Assess clinical response at the end of paclitaxel and at the end of neoadjuvant chemotherapy | tumor measurements by caliper every cycle and by ultrasound at the end of chemotherapy | after 24 treatment weeks' | 
| To correlate serum levels of insulin, protein C and HbA1 (after treatment) with clinical and pathologic response | correlation between serum levels of insuline levels, HbA1 and PCR and PCR | safter 24 treatment weeks' | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally advanced breast cancer, Neoadjuvant chemotherapy, Metformin, Pathologic Complete Response