Metformin for the Treatment of Insulin Resistance in Women With Stage I-III Breast Cancer Completing Chemotherapy

NCT06763328 | Recruiting Phase 3 DMC

• 4 other identifiers: 24363NCI-2024-10402P30CA033572U54CA285116
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 3

Brief Summary

This phase III trial evaluates how often women develop insulin resistance and type-2 diabetes and compares metformin with usual care to usual care alone in treating insulin resistance in women with stage I-III breast cancer after chemotherapy. Insulin resistance occurs when cells stop responding to insulin and is a risk factor for developing diabetes and heart disease. Higher levels of insulin have been shown to be associated with aggressive breast cancer. Metformin hydrochloride decreases the amount of glucose (a type of sugar) released into the bloodstream from the liver and increases the body's use of the glucose. Metformin as well as standard of care diet and exercise education is known to lower blood sugar. However, chemotherapy may accelerate metabolic disorders, such as high blood sugar, and the impact of metformin in these breast cancer survivors is not known. Giving metformin with usual care may be more effective than usual care alone in preventing or reversing insulin resistance in women with stage I-III breast cancer after chemotherapy.

Conditions

Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Invasive Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Hemoglobin A1c (Hgb A1c) normalization

  Will be defined as Hgb A1c \< 5.7%. Will be compared across groups (metformin + standard of care/usual medical care versus standard of care/usual medical care alone) using chi-square statistics. Data will be summarized using counts and percentages.

  Up to 12 months

Secondary Outcomes (1)

• HgbA1c normalization

  At 3, 6, 12 and 24 months

Study Arms (2)

Arm I (standard of care, metformin)

EXPERIMENTAL

Patients receive standard of care healthy diet and exercise handouts and extended release metformin PO QD for 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the study.

Procedure: Biospecimen Collection; Other: Educational Intervention; Drug: Extended Release Metformin Hydrochloride; Other: Questionnaire Administration

Arm II (standard of care)

ACTIVE COMPARATOR

Patients receive standard of care healthy diet and exercise handouts on study. Additionally, patients undergo blood sample collection throughout the study.

Procedure: Biospecimen Collection; Other: Educational Intervention; Other: Questionnaire Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (standard of care, metformin); Arm II (standard of care)

Educational Intervention OTHER

Receive standard of care healthy diet and exercise handouts

Also known as: Education for Intervention, Intervention by Education, Intervention through Education, Intervention, Educational

Arm I (standard of care, metformin); Arm II (standard of care)

Extended Release Metformin Hydrochloride DRUG

Given PO

Also known as: ER Metformin Hydrochloride, Extended-release Metformin Hydrochloride, Glucophage XR, Glumetza, Metformin Hydrochloride Extended Release

Arm I (standard of care, metformin)

Questionnaire Administration OTHER

Ancillary studies

Arm I (standard of care, metformin); Arm II (standard of care)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Agreement to allow lab draw of approximately 26 mL of blood (less than 3 tablespoons)
• To check blood counts, organ function and disease at baseline and 12 months
• Clinical labs at baseline, 3 months, 6 months,12 months, and 24 months
• Research labs at baseline, 6 months,12 months, and 24 months
• Age: ≥ 18 years
• Female sex assigned at birth
• Ability to read and understand English or Spanish for questionnaires
• Diagnosis of estrogen receptor (ER)-negative /HER2-wild type or -amplified invasive mammary carcinoma stages I-III
• Receive systemic treatment for breast cancer treatment
• Completed treatment for stage 1-3 breast cancer within 90 days to 5 years and are disease free
• Women who receive drugs for weight loss - e.g. semaglutide - prior to diagnosis are eligible for this protocol and can continue the drug during the intervention

You may not qualify if:

• Currently taking metformin or any other oral antidiabetic medications. Weight loss medications are permitted - e.g. semaglutide
• Taking tamoxifen or aromatase inhibitor
• Contraindication to metformin prevention such as acute hypersensitivity or allergic reaction to metformin
• Participants with acute or chronic renal insufficiency (a glomerular filtration rate \[GFR\] \< 30 mL/min/1.73m\^2) or those with acute renal insufficiency of any severity due to hepato-renal syndrome or in the peri-operative liver transplantation period
• Previously diagnosed type 1 or type 2 diabetes
• Patients pregnant or within 1 year of pregnancy and completion of lactation (pregnancy tests are standard of care \[SOC\] for initiation of chemotherapy)
• Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• An employee who is under the direct/indirect supervision of the principal investigator (PI)/a co-investigator/the study manager and/or a direct study team member
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

NOT YET RECRUITING

University of California-Riverside

Riverside, California, 92521, United States

NOT YET RECRUITING

MeSH Terms

Interventions

Specimen Handling; Early Intervention, Educational; Educational Status; Methods; Metformin

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Child Health Services; Community Health Services; Health Services; Health Care Facilities Workforce and Services; Preventive Health Services; Socioeconomic Factors; Population Characteristics; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Victoria L Seewaldt

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2025
• First Posted: January 8, 2025
• Study Start: December 16, 2024
• Primary Completion (Estimated): June 16, 2029
• Study Completion (Estimated): June 16, 2029
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

US (3)