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

NCT ID: NCT06763328

Last Updated: 2026-01-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-16

Study Completion Date

2029-06-16

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVE:

I. To determine if extended release metformin hydrochloride (metformin) can normalize glycosylated hemoglobin (HgbA1c) (\< 5.7%) for women breast cancer survivors with HgbA1c between 5.7-6.4%.

EXPLORATORY OBJECTIVES:

I. To investigate whether metformin treatment of insulin resistance (versus standard of care alone) alters epigenetic changes (chromatin acetylation, chromatin opening, and methylation) and the level of inflammatory cytokines. (Pilot) II. To investigate whether normalization of HgbA1c alters epigenetic changes (chromatin acetylation, chromatin opening, and methylation) and the level of inflammatory cytokines. (Pilot)

OUTLINE: Patients are randomized to 1 of 2 arms.

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

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

After completion of study treatment, patients are followed up at 30 days and in 12 months.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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Arm I (standard of care, metformin)

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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Educational Intervention

Intervention Type OTHER

Receive standard of care healthy diet and exercise handouts

Extended Release Metformin Hydrochloride

Intervention Type DRUG

Given PO

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Arm II (standard of care)

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

Group Type ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Educational Intervention

Intervention Type OTHER

Receive standard of care healthy diet and exercise handouts

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Interventions

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Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Educational Intervention

Receive standard of care healthy diet and exercise handouts

Intervention Type OTHER

Extended Release Metformin Hydrochloride

Given PO

Intervention Type DRUG

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection Education for Intervention Intervention by Education Intervention through Education Intervention, Educational ER Metformin Hydrochloride Extended-release Metformin Hydrochloride Glucophage XR Glumetza Metformin Hydrochloride Extended Release

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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)
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

City of Hope Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Victoria L Seewaldt

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

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City of Hope Medical Center

Duarte, California, United States

Site Status RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status NOT_YET_RECRUITING

University of California-Riverside

Riverside, California, United States

Site Status NOT_YET_RECRUITING

Countries

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United States

Facility Contacts

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Victoria L. Seewaldt

Role: primary

626-218-6321

Shankar Subramaniam

Role: primary

858-822-0986

Kendrick A. Davis

Role: primary

951-827-2031

Other Identifiers

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24363

Identifier Type: -

Identifier Source: org_study_id

NCI-2024-10402

Identifier Type: REGISTRY

Identifier Source: secondary_id

24363

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U54CA285116

Identifier Type: NIH

Identifier Source: secondary_id

View Link

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