Metformin and Omega-3 Fatty Acids in Woman With a History of Early Stage Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine whether it is feasible to give a combination of Metformin and omega-3 fatty acids for one year to women with a history of early stage breast cancer. We will also evaluate whether the metformin and omega-3 fatty acids combination causes changes in breast tissue, blood, and mammograms.

Detailed Description
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Metformin is a medication used to treat and prevent diabetes and omega-3 fatty acids has been shown to lower cholesterol and improve cardiovascular health. Research has shown that Metformin and omega-3 fatty acids may also be effective in preventing cancer. In this study, we want to find out what effects, good and/or bad, the Metformin and omega-3 fatty acids combination has on you and your risk of developing a new breast cancer.

Official Title
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Pilot Biomarker Modulation Study of Metformin and Omega-3 Fatty Acids in Woman With a History of Early Stage Breast Cancer

Conditions
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Stage 0 Breast Carcinoma, Breast Neoplasms, Stage I Breast Carcinoma, Stage II Breast Carcinoma, Stage III Breast Carcinoma

Intervention / Treatment
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* Drug: Metformin
* Drug: Omega-3 fatty acids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of histologically-confirmed stage 0, I, II, or III breast carcinoma without evidence of disease at trial entry. Participants with a resected local recurrence are eligible Minimum of 6 months since last chemotherapy, biologic therapy (i.e., trastuzumab), radiation therapy, and/or breast surgery and no evidence of recurrent disease Minimum of 6 months since completion of adjuvant tamoxifen (tamoxifen is known to lower mammographic density119-121). Current use of a third generation aromatase inhibitor [AI] (i.e., anastrozole, letrozole, exemestane) is permitted provided that the participant has been on a stable dose for the past 6 months Age 21 to 75 years. Both pre- and postmenopausal women will be included in this study. We will exclude perimenopausal women, defined as menstrual cycle irregularity (variable cycle length that differs from normal by more than 7 days) and an Follicle-Stimulating Hormone (FSH) greater than 20 mili international units Negative serum pregnancy testing Normal mammogram of the contralateral breast within the past 12 months, defined as no new suspicious calcifications or other abnormal findings warranting a breast biopsy Eastern Cooperative Oncology Group (ECOG) performance status less than 2 Participants must have normal organ and marrow function within 28 days prior to randomization Body mass index (BMI) greater than or equal to 25 kilograms per meter squared or baseline fasting glucose of less than 126 milligrams per deciliter Participants must have a baseline mammographic density greater than or equal to 25 percent based upon the Breast Imaging Reporting and Data System (BIRADS) density score of 2, 3, or 4. Women with a baseline mammographic density of less than 25 percent (BIRADS Score= 1) will not be eligible Willingness to abstain from all omega-3 fish oil supplements for 30 days prior to baseline evaluation and during the study intervention Willingness to comply with all study interventions and follow-up procedures Ability to understand and willingness to sign a written informed consent document Exclusion Criteria: History of histologically-confirmed bilateral breast cancer History of or plans for bilateral mastectomies Evidence of metastatic breast cancer Prior radiation therapy or implant in the contralateral breast Known diabetes (type 1 or 2) or baseline fasting glucose greater than 126 milligrams per deciliter Any condition associated with increased risk of metformin-associated lactic acidosis (e.g., congestive heart failure defined as New York Heart Association [NYHA] Class III or IV functional status, history of acidosis of any type, intake of 3 or more alcoholic beverages per day on average over the past 6 months) Currently taking metformin, sulfonylureas, thiazolidinediones, or insulin for any reason History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin or omega-3 fatty acids Receiving hormone replacement therapy, tamoxifen, or raloxifene within 6 months of trial entry Participants may not be receiving any other investigational agents for 30 days prior to baseline evaluation and during the study intervention Any omega-3 fatty acids should not be taken for 30 days prior to baseline evaluation and during the study intervention. If participants are consuming any of these items and would like to participate in this study, then a 30-day washout period will be required. - Uncontrolled or significant co-morbid illness patients receiving active chemotherapy or radiotherapy; or psychiatric illness/social situations that would limit compliance with study requirements

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Main Arm<br>Open Label- Metformin and Omega-3 fatty acids for 12 months post baseline data collection. | Drug: Metformin<br>* Metformin 850mg, oral, twice a day for 12 months<br>* Other names: N,N-dimethyl biguanide hydrochloride;Drug: Omega-3 fatty acids<br>* Omega-3 fatty acids 2 capsules (560 mg each) oral, twice a day for 12 months<br>* Other names: Docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants successfully completing the 1-year intervention | The primary objective is to assess the safety and feasibility of a one-year intervention of metformin and omega-3 fatty acids in early stage breast cancer patients who completed adjuvant treatment. | 12 months (approximately) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent in reduction of mammographic density | Determine the efficacy of these drug interventions in reducing mammographic density | baseline, 12 months | 
| Change in fasting serum insulin microunits per milliliter | Determine the efficacy of these drug interventions in modulating markers of insulin signaling. | baseline, month 3, 6, 9, and 12 | 
| Change in C-peptide nanograms per milliliter | Determine the efficacy of these drug interventions in modulating markers of insulin signaling. | baseline, month 3, 6, 9, and 12 | 
| Change in insulin-like growth factor 1 (IGF-1) nanograms per milliliter | Determine the efficacy of these drug interventions in modulating markers of insulin signaling. | baseline, month 3, 6, 9, and 12 | 
| Change in insulin-like growth factor binding protein 1 (IGFBP-1) nanograms per milliliter | Determine the efficacy of these drug interventions in modulating markers of insulin signaling. | baseline, month 3, 6, 9, and 12 | 
| Change in insulin-like growth factor binding protein 3 (IGFBP-3) milligrams per liter | Determine the efficacy of these drug interventions in modulating markers of insulin signaling. | baseline, month 3, 6, 9, and 12 | 
| Change in fasting serum glucose milligrams per deciliter | Determine the efficacy of these drug interventions in modulating metabolic profile markers. | baseline, month 3, 6, 9, and 12 | 
| Change in total cholesterol milligrams per deciliter | Determine the efficacy of these drug interventions in modulating metabolic profile markers. | baseline, month 3, 6, 9, and 12 | 
| Change in high-density lipoprotein (HDL) milligrams per deciliter | Determine the efficacy of these drug interventions in modulating metabolic profile markers. | baseline, month 3, 6, 9, and 12 | 
| Change in low-density lipoprotein (LDL) milligrams per deciliter | Determine the efficacy of these drug interventions in modulating metabolic profile markers. | baseline, month 3, 6, 9, and 12 | 
| Change in Leptin microunits per liter | Determine the efficacy of these drug interventions in modulating metabolic profile markers. | baseline, month 3, 6, 9, and 12 | 
| Change in adiponectin micrograms per milliliter | Determine the efficacy of these drug interventions in modulating metabolic profile markers. | baseline, month 3, 6, 9, and 12 | 
| Change in serum C-reactive protein milligrams per deciliter | Determine the efficacy of these drug interventions in modulating inflammatory markers. | baseline, month 3, 6, 9, and 12 | 
| Change in Interleukin-6 picograms per milliliter | Determine the efficacy of these drug interventions in modulating inflammatory markers. | baseline, month 3, 6, 9, and 12 | 
| Change in body mass index (BMI) | Determine the efficacy of these drug interventions in modulating anthropometric measures. | baseline, month 3, 6, 9, and 12 | 
| Change in systolic blood pressure | Determine the efficacy of these drug interventions in modulating anthropometric measures. | baseline, month 3, 6, 9, and 12 | 
| Change in diastolic blood pressure | Determine the efficacy of these drug interventions in modulating anthropometric measures. | baseline, month 3, 6, 9, and 12 | 
| Change in homeostatus model assessment (HOMA) score | Determine the efficacy of these drug interventions in modulating anthropometric measures. | baseline, month 3, 6, 9, and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Early Stage