Anatomic Stage I Breast Cancer AJCC v8Phase 3NCT06763328
Metformin for the Treatment of Insulin Resistance in Women With Stage I-III Breast Cancer Completing Chemotherapy
A Phase 3 study testing Biospecimen Collection, Educational Intervention and Extended Release Metformin Hydrochloride in people with Anatomic Stage I Breast Cancer AJCC v8 and Anatomic Stage II Breast Cancer AJCC v8, run by City of Hope Medical Center at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8
- What is being tested?
- Biospecimen Collection, Educational Intervention and Extended Release Metformin Hydrochloride
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 3 sitesUnited States
- Study dates
- 13 Jan 2025to 16 Jun 2031
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented informed consent of the participant and/or legally authorized representative
- Agreement to allow lab draw of approximately 26 mL of blood (less than 2 tablespoons)
- To check blood counts, organ function and disease at baseline and 12 months
- Review of clinical charts at pre-registration* (refer to Study Calendar), baseline, 3 months, 6 months,12 months, and 24 months
- Research labs at baseline, 6 months,12 months, and 24 months
- Age: ≥ 18 years
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- Female sex assigned at birth
- Ability to read and understand English or Spanish for questionnaires
- Diagnosis of invasive breast cancer stages I-III
- Completed adjuvant treatment for Stage 1-3 breast cancer within 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.
Who cannot join
- 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] < 60 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
- Bilirubin of >2.5 mg/dL (normal range 0.1-1.2 mg/dL).
- Previously diagnosed type 1 or type 2 diabetes
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- Patients pregnant or within 1 year of pregnancy and completion of lactation (to be determined at randomization).
- 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)
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
City of Hope Medical Center
Duarte, California, 91010
Victoria L. Seewaldt, 626-218-6321, vseewaldt@coh.org
Victoria L. Seewaldt
- Not yet recruiting
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Shankar Subramaniam, 858-822-0986, shsubramaniam@ucsd.edu
Shankar Subramaniam
- Not yet recruiting
University of California-Riverside
Riverside, California, 92521
Kendrick A. Davis, 951-827-2031, kdavis@ucr.edu
Kendrick A. Davis
About this study
Official title: Metformin (Dimethylbiguanide) and Insulin Resistance in Women Completing Neoadjuvant and/or Adjuvant Cytotoxic Treatment of Stage I-III Breast Cancer
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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
- Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Invasive Breast Carcinoma
- Being tested
- Biospecimen Collection, Educational Intervention, Extended Release Metformin Hydrochloride, Questionnaire Administration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
Educational InterventionOther
Also called Education for Intervention, Intervention by Education, Intervention through Education, Intervention, Educational
Receive standard of care healthy diet and exercise handouts
Extended Release Metformin HydrochlorideDrug
Also called ER Metformin Hydrochloride, Extended-release Metformin Hydrochloride, Glucophage XR, Glumetza
Given PO
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Biospecimen Collection; Other: Educational Intervention; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 12 months
Secondary outcomes (1)
HgbA1c normalization
Will compare HgbA1c normalization as well as pairwise t-tests across treatment groups to examine the magnitude of change in HgbA1c.
Measured: At 3, 6, 12 and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2025
- Study start13 Jan 2025
- Primary completion16 Jun 2031 (estimated)
- Study completion16 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anatomic Stage I Breast Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Victoria L Seewaldt, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06763328
- Sponsor's protocol ID
- 24363
- Other IDs
- NCI-2024-10402, 24363, P30CA033572, U54CA285116
- Status last verified
- Oct 2026
- First submitted
- 2 Jan 2025
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No