Metformin Plus Neoadjuvant Chemotherapy in Breast Cancer

Instituto Nacional de Cancerologia de Mexico60 enrolled

Overview

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

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Locally Advanced Malignant Neoplasm

Interventions

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Time frame: pCR will be assesed after 24 weeks of treatment

Secondary Outcomes

Safety analysis

For safety analysis we are going to use NCTC criteria version 3.0

Time frame: 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

Time frame: 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

Time frame: safter 24 treatment weeks'