Metformin and Nightly Fasting in Women With Early Breast Cancer

• Status: Not yet recruiting
• Trial end date: 2024-11-30
• Target enrollment: 0
• Participant gender: Female

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 breaset 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Metformin

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• Body mass index (BMI) < 18.5 Kg/m^2

• Previous treatment for breast cancer including chemotherapy and endocrine therapy

• Women who are planned to receive neoadjuvant therapy (HER2+ve T2 or N+ve IBC or women < 50 years with luminal B IBC)

• Triple negative breast cancer (BC)

• 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)

• Concomitant use of topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide)

• Pregnant women are excluded from this study because even though published data from post-marketing studies have not reported a clear association between metformin hydrochloride extended release and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin hydrochloride extended release was used during pregnancy, these studies cannot definitely establish the absence of any metformin hydrochloride extended release associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with metformin hydrochloride extended release, breastfeeding should be discontinued if the mother is treated with metformin hydrochloride extended release. Moreover, prolonged fasting is not recommended in pregnant woman

• Women who practice any type of intermittent fasting program

• Women who will not have anyone available to assist them in case of need