Metformin and Nightly Fasting in Women With Early Breast Cancer

NCT05023967 | Active Not Recruiting Phase 2 DMC FDA Drug

• 8 other identifiers: 2021-0901NCI-2021-08921B115UCS20192021-000134-342021-09-01Pending3MDA20-02-01UG1CA242609
• Study Type: interventional
• Target: 120
• Locations: 2 countries
• Sites: 3

Brief Summary

This phase IIb trial studies the combined effect of prolonged nightly fasting and metformin hydrochloride extended release in decreasing breast tumor cell proliferation and other biomarkers of breast cancer. Preventing invasive breast cancer or DCIS. Metformin is widely used to treat type II diabetes and is associated with a decreased risk of cancer and death in diabetic individuals. Intermittent fasting may protect cancer patients from the toxic effects of chemotherapy agents without causing chronic weight loss. The combination of intermittent fasting and metformin may reduce breast cancer growth and may be used in women at risk for breast cancer or other cancers associated with being overweight.

Conditions

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Breast Ductal Carcinoma In Situ; Invasive Breast Carcinoma

Outcome Measures

Primary Outcomes (3)

• Frequency of occurrence of dose limiting toxicity

  Defined as a hypoglycemic event requiring permanent discontinuation of study treatment or any grade 3 or greater adverse event possibly, probably, or definitely related to the study drug.

  Up to 4-6 weeks

• Change in pre-post treatment Ki67 labeling index in invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) (in the absence of IBC)

  Generalized linear models will be used to assess differences between treatment arms for Ki67. Log transformation will be considered to obtain normal distribution of residuals. Will also evaluate the need to adjust for baseline characteristics and significant confounders (such as body mass index \[BMI\] and HER2 status).

  Baseline up to 4-6 weeks

• Difference in post-treatment adjacent DCIS (in the presence of IBC), if present, or intraepithelial neoplasia Ki67 between arms

  Generalized linear models will be used to assess differences between treatment arms for Ki67. Log transformation will be considered to obtain normal distribution of residuals. Will also evaluate the need to adjust for baseline characteristics and significant confounders (such as BMI and HER2 status).

  Post-treatment (4-6 weeks)

Secondary Outcomes (11)

• Change in circulating biomarkers

  Baseline up to 4-6 weeks

• Change of CIP2A-PP2A-GSK3beta-MCL-1 axis in cancer tissue

  Baseline up to 4-6 weeks

• Change of Ki67 in cancer tissue

  Baseline up to 4-6 weeks

• Difference of M30

  Post-treatment

• Difference of phosphorylated S6

  Post-treatment

Study Arms (2)

Arm I (fasting, glucose monitoring, counseling, metformin)

EXPERIMENTAL

Patients fast for \>= 16 hours every night and use the continuous glucose monitoring system for 4-6 weeks. Patients also receive nutritional counseling sessions on days 0 and 10. Beginning week 2, patients also receive metformin hydrochloride extended release PO QD until the day of surgery. Treatment continues for 4-6 weeks (until surgery) in the absence of disease progression or unacceptable toxicity. Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43).

Procedure: Biospecimen Collection; Drug: Extended Release Metformin Hydrochloride; Other: Monitoring; Other: Nutritional Assessment; Other: Short-Term Fasting

Arm II (glucose monitoring)

ACTIVE COMPARATOR

Patients continue their usual dietary pattern and use the continuous glucose monitoring system for 4-6 weeks (until surgery). Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43).

Procedure: Biospecimen Collection; Other: Monitoring

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood and tissue samples

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

Arm I (fasting, glucose monitoring, counseling, metformin); Arm II (glucose monitoring)

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 (fasting, glucose monitoring, counseling, metformin)

Monitoring OTHER

Use continuous glucose monitoring system

Also known as: monitor

Arm I (fasting, glucose monitoring, counseling, metformin); Arm II (glucose monitoring)

Nutritional Assessment OTHER

Receive nutritional counseling

Also known as: Dietary Assessment, dietary counseling, nutritional counseling

Arm I (fasting, glucose monitoring, counseling, metformin)

Short-Term Fasting OTHER

Perform intermittent fasting

Also known as: Intermittent Fasting, Short-term Intermittent Fasting

Arm I (fasting, glucose monitoring, counseling, metformin)

Eligibility Criteria

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

You may qualify if:

• Women with histologically confirmed luminal (ER+ve and/or progesterone \[PgR\]+ve \>= 1%) operable IBC (cT1-2, cN0-1, Mx) candidate to elective surgery and not to neo-adjuvant treatment. Women with larger tumors who refuse neo-adjuvant chemotherapy before surgery can also be eligible. Luminal HER2+ve (cT1, cN0) IBC and DCIS are also eligible
• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Leukocytes \>= 3,000/microliter
• Absolute neutrophil count \>= 1,500/microliter
• Platelets \>= 100,000/microliter
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x institutional upper limit of normal
• Creatinine within normal institutional limits
• Creatinine clearance estimated with Cockcroft-Gault formula \> 45 mL/min
• Female participants of child-bearing potential must agree to use contraception such as barrier method of birth control or abstinence, prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she has to inform her study physician immediately. The effects of metformin hydrochloride extended release on the developing human fetus at the recommended therapeutic dose are unknown
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Body mass index (BMI) \< 18.5 Kg/m\^2
• Previous treatment for breast cancer including chemotherapy and endocrine therapy within the last 12 months
• Women who are planned to receive neoadjuvant therapy
• Triple negative breast cancer (BC)
• Patients with a history of cancer within the last year. NOTE: Non melanoma skin cancer is allowed.
• Documented history of symptomatic hypoglycemia
• Diabetic patients or participants with fasting glucose level \>= 126 mg/dL
• Known hypersensitivity or intolerance to metformin hydrochloride extended release
• Participants should not be receiving any other investigational agents
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• History of lactic acidosis
• Liver dysfunction including chronic active hepatitis and cirrhosis not compensated
• History of vitamin B12 deficiency or megaloblastic anemia
• Chronic use of large doses of diuretics (e.g., \> 80 mg furosemide)
• Current use of oral hormonal contraceptives or female hormones in the last four weeks or 5 half-lives, excluding vaginal creams and intrauterine devices (IUDs)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Galliera Hospital

Genoa, 16128, Italy

Location

European Institute of Oncology

Milan, 20141, Italy

Location

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating

Interventions

Specimen Handling; Metformin; Nutrition Assessment

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Biguanides; Guanidines; Amidines; Organic Chemicals; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Epidemiologic Measurements; Public Health; Environment and Public Health

Study Officials

• Parijatham Thomas, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2021
• First Posted: August 27, 2021
• Study Start: April 4, 2023
• Primary Completion: December 9, 2025
• Study Completion (Estimated): December 16, 2026
• Last Updated: January 5, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1); IT (2)