Metformin Hydrochloride vs. Placebo in Overweight or Obese Patients at Elevated Risk for Breast Cancer

NCT ID: NCT01793948

Last Updated: 2018-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-16
• Study Completion Date: 2018-01-09

Brief Summary

This randomized clinical trial studies metformin hydrochloride in overweight or obese patients at elevated risk for breast cancer. Metformin hydrochloride may decrease the expression of early tumor makers in breast tissue of patients at increased risk for breast cancer

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the changes in the signal pathway profiling of breast tissue using reverse phase proteomics in tissue biopsy of overweight or obese women at elevated risk for breast cancer treated with metformin (metformin hydrochloride) (850mg orally twice a day) for 12 cycles.

SECONDARY OBJECTIVES:

I. To determine the effect of metformin on breast tissue density of overweight or obese women at elevated risk for breast cancer using qualitative mammographic fat density criteria.

II. To determine the effect of metformin on the insulin axis in serum of overweight or obese women at elevated risk for breast cancer treated with metformin (850mg orally twice a day) for 12 cycles.

III. To determine the toxicities associated with metformin.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive metformin hydrochloride by mouth once daily on days 1-30 in course 1 and twice daily on days 1-30 thereafter. Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo by mouth once daily on days 1-30 in course 1 and twice daily on days 1-30 thereafter. Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for up to 5 years.

Conditions

Breast Cancer; Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Arm I (metformin hydrochloride)

Patients receive metformin hydrochloride by mouth once daily on days 1-30 in course 1 and twice daily on days 1-30 thereafter. Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

metformin hydrochloride

Intervention Type: DRUG

Given PO

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Arm II (placebo)

Patients receive placebo by mouth once daily on days 1-30 in course 1 and twice daily on days 1-30 thereafter. Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Given PO

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

metformin hydrochloride

Given PO

Intervention Type: DRUG

placebo

Given PO

Intervention Type: OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Glucophage; PLCB

Eligibility Criteria

Inclusion Criteria

• Patients must be post-menopausal women; post-menopausal women are defined as: (1) those >= 50 years of age who had not menstruated during the preceding 12 months or who had castrate follicle-stimulating hormone levels (> 40 IU/L), (2) those who had undergone a bilateral oophorectomy
• Patients must be at elevated risk for breast cancer based on strong family history or a history of breast biopsy documenting atypical hyperplasia anytime in the past; for this study strong family history is defined as having:

• 1 first-degree (parent, offspring, sibling) relative =< 50 years old when diagnosed with breast cancer, or
• >= 2 first-degree relatives of any age when diagnosed with breast cancer, or
• >= 2 second-degree (aunts, uncles, grandparents, grandchildren, nieces, nephews, or half-siblings) maternal or paternal relatives diagnosed with breast cancer and at least 1 diagnosed at =< 50 years of age
• Patients must have a body mass index (BMI) >= 25.0 as calculated by the formula: weight in pounds / height squared x 703 = BMI; a BMI of:

• 18.5-24.9 is considered normal;
• 25.0-29.9 is considered overweight;
• 30.0+ is regarded as obese
• Patients must be willing to complete a bilateral mammogram at baseline with repeat exam after 12 cycles of protocol therapy; patients who have had a mammogram within 1 month prior to registration to protocol therapy will not need to repeat the exam
• Patients must be willing to provide a core tissue biopsy at baseline and with repeat tissue collection after 12 cycles of protocol therapy
• White blood cell (WBC) >= 3.0 x 109/L
• Granulocytes (polymorphs + bands) >= 1.5 x 109/L
• Platelets >= 100 x 109/L
• Hemoglobin >= 110 g/L
• Aspartate aminotransferase (AST) =< 1.8 X upper limit of normal (ULN)
• Alanine aminotransferase (ALT) =< 1.8 X ULN
• Alkaline phosphatase =< 2 X ULN
• Serum creatinine =< 115 umol/L (1.3mg/dL)
• Serum bilirubin =< institution ULN (except for subjects with Gilbert's Disease who are eligible despite elevated serum bilirubin level)
• 12 hour fasting glucose level < 7.0 mmol/L
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1 within 28 days of registration
• Life expectancy of >= 5 years
• Subjects must be accessible for treatment, adverse event tracking and follow-up as determined by the treating physician
• Subject consent and authorization for the release of health information must be obtained according to local institutional guidelines

Exclusion Criteria

• No history of any malignancy except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for >= 5 years
• No known diabetes (type 1 or 2) or baseline fasting glucose >= 7.0 mmol/L
• No known hypersensitivity or intolerance to metformin
• No 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; habitual intake of 3 or more alcoholic beverages per day)
• No current treatment with metformin, sulfonylureas, thiazolidinediones or insulin for any reason
• No breastfeeding
• No concurrent or planned participation in randomized trials of weight loss or exercise interventions or trials targeting insulin, insulin-like growth factor 1 (IGF-1) or their receptors

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Anna Maria Storniolo

OTHER

Sponsor Role: lead

Responsible Party

Anna Maria Storniolo

Professor of Clinical Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Anna Maria Storniolo, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University Melvin and Bren Simon Cancer Center

Locations

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Countries

United States

Other Identifiers

NCI-2013-00422

Identifier Type: REGISTRY

Identifier Source: secondary_id

1301010355

Identifier Type: OTHER

Identifier Source: secondary_id

IUCRO-0365

Identifier Type: -

Identifier Source: org_study_id