Metformin Use to Reduce Disparities in Newly Diagnosed Breast Cancer

NCT04741204 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: RP-20-013
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Breast cancer is one of the most common malignancies in women globally, with \~1.4 million new cases diagnosed annually Breast cancer is one of the leading causes of cancer-related morbidity and mortality among women worldwide. While diabetes/insulin-resistance and breast cancer are distinct diseases, insulin-signaling plays a central role in both illnesses. Insulin activates key cancer processes including epithelial-mesenchymal transition (EMT), tissue inflammation, motility, and angiogenesis. There are key opportunities to impact and prevent hyperinsulinemia during breast cancer prevention, surgical assessment, and chemotherapy. Given the high prevalence of undiagnosed pre-diabetes and diabetes in the United States and worldwide, preoperative screening to identify such patients prior to surgical intervention is warranted. While it is not standard of care to test for insulin-resistance during the course of breast cancer screening and treatment, it is standard of care to screen and test high risk women for insulin-resistance as part of whole woman care. Given the important role insulin signaling plays in driving signaling pathways that promote aggressive cancer biology, more attention should be paid by cancer physicians to screening and treating insulin resistance. Several studies have reinforced a link between breast cancer risk and diabetes. Moreover, metformin significantly reduces breast cancer risk, compared to patients who are not using metformin and is independent of diabetes status. As metformin has an association with decreased breast cancer recurrence, as well as potentially improved survival, disparities in insulin resistance between black and white women with breast cancer is important to investigate. It is hypothesized that metformin decreases the development of resistance in breast cancer cells, thereby allowing current chemotherapy agents to work synergistically with metformin. Our objective is to elucidate whether or not metformin is efficacious in improving insulin resistance in black and white women with breast cancer and if racial disparities in breast cancer prognosis can be partially explained by differences in pre-diagnosis insulin resistance which are improved with metformin therapy.

Conditions

Breast Cancer Stage; Insulin Resistance; Racial Bias

Keywords

metformin; breast cancer; racial disparity; tumor regression

Outcome Measures

Primary Outcomes (1)

• Tumor progression

  breast cancer response rate to metformin treatment prior to surgery pathologic response to treatment at surgery will be defined by the following categories: 0-no response; 1-partial response; and 2-complete response with metformin therapy

  6 to 12 months

Secondary Outcomes (6)

• Fasting glucose levels

  6 to 12 months

• Mean glucose stimulated levels after an OGTT

  6 to 12 months

• Homeostatic Model Assessment of Insulin Resistance Index (HOMA-IR)

  6 to 12 months

• Matsuda's insulin sensitivity index (SIOGTT)

  6 to 12 months

• Early pancreatic β-cell response

  6 to 12 months

Other Outcomes (1)

• Recurrence rate of breast cancer

  3 years

Study Arms (2)

White women

EXPERIMENTAL

White women on metformin Extended release 750 mg BID

Drug: Metformin Extended Release Oral Tablet

Black women

EXPERIMENTAL

Black women on metformin Extended release 750 mg BID

Drug: Metformin Extended Release Oral Tablet

Interventions

Metformin Extended Release Oral Tablet DRUG

initial dose of metformin of 750 mg Q.D. (with dinner) for 3-4 weeks. They then will be increased to the final dose of 750 mg BID (breakfast and dinner) until the end of the study.

Also known as: metformin XR, metformin ER

Black women; White women

Eligibility Criteria

• Age: 18 Years - 80 Years
• Gender Eligibility Details: genetic XX
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-Hispanic white or black females
• Age \> = 18 years
• English speaking
• Newly diagnosed breast cancer
• BMI \> = 25 (must be overweight)
• Insulin-resistant (as determined by 2 hour 75 gm oral glucose tolerance test (OGTT)). Concentrations and trajectories of insulin and glucose at 0, 30, 60, and 120 min during an oral glucose tolerance test will undergo mathematical modeling. The numbers for defining insulin resistance have been established in the Woman's Laboratory and are interpreted by the pathologists.

You may not qualify if:

• Metastatic Disease
• Current diagnosis of Diabetes or diagnosed with diabetes (as determined by HbA1C\> 6.5)
• Having surgery prior to chemotherapy
• Medical conditions for which metformin is contraindicated (gastrointestinal and renal failure),
• Abnormal CBC (defined by a baseline platelet count of less than 130 and a baseline absolute neutrophil count of less than 1000). In addition, baseline hemoglobin of less than 10, if there is no evidence of a concurrent nutritional deficiency (like iron). \[Patients simply needing something like iron to correct the anemia will not be excluded\].

Sponsors & Collaborators

• Woman's: lead
• Our Lady of the Lake Hospital: collaborator
• American Cancer Society, Inc.: collaborator
• Pfizer: collaborator

Study Sites (1)

Woman's Hospital

Baton Rouge, Louisiana, 70815, United States

Location

MeSH Terms

Conditions

Insulin Resistance; Racism; Breast Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Prejudice; Social Behavior; Behavior; Social Discrimination; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Ericka Seidemann, MA

  Woman's Hospital, Louisiana

  STUDY CHAIR

• Cynthia Harper-Weinstein

  Mary Bird Perkins Cancer center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Breast cancer tumor response rate to metformin treatment prior to surgery in black vs. white women.

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: February 5, 2021
• Study Start: September 1, 2022
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: July 6, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)