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

NCT01793948 | Completed Early Phase 1 DMC FDA Drug

• 3 other identifiers: IUCRO-0365NCI-2013-004221301010355
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Conditions

Breast Cancer; Obesity

Outcome Measures

Primary Outcomes (1)

• Changes in the phosphorylation of proteins after metformin exposure

  Reverse phase proteomic assays (RPPA) will be performed to measure changes in the phosphorylation of proteins after metformin exposure. Changes in the phosphorylation of proteins after metformin exposure will be calculated and compared using two-sample t-tests. As a supplemental analysis, analysis of covariance (ANCOVA) will be used to model the 12 month levels adjusted for baseline. Assumptions for analysis will be checked and non-parametric methods used if needed; however it is expected that the data will be normally distributed on the log scale.

  Baseline and 12 months

Secondary Outcomes (2)

• Changes in ordinal level of breast density

  Baseline and 12 months

• Proportion of patients experiencing adverse events assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  Up to 30 days

Study Arms (2)

Arm I (metformin hydrochloride)

EXPERIMENTAL

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.

Drug: metformin hydrochloride; Other: laboratory biomarker analysis

Arm II (placebo)

PLACEBO COMPARATOR

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.

Other: placebo; Other: laboratory biomarker analysis

Interventions

metformin hydrochloride DRUG

Given PO

Also known as: Glucophage

Arm I (metformin hydrochloride)

placebo OTHER

Given PO

Also known as: PLCB

Arm II (placebo)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (metformin hydrochloride); Arm II (placebo)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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:
• is considered normal;
• is considered overweight;
• + 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Anna Maria Storniolo: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Obesity

Interventions

Metformin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Anna Maria Storniolo, MD

  Indiana University Melvin and Bren Simon Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Clinical Medicine

Study Record Dates

• First Submitted: February 14, 2013
• First Posted: February 18, 2013
• Study Start: April 16, 2013
• Primary Completion: January 9, 2018
• Study Completion: January 9, 2018
• Last Updated: March 30, 2018

Record last verified: 2018-03

Locations

US (1)