Metformin + Fasting for Breast Cancer

Not currently recruiting at 3 trial locations

Overseen By Parijatham Thomas, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Metformin

Must not be taking: Diuretics, Carbonic anhydrase inhibitors

Disqualifiers: Diabetes, Hypoglycemia, Liver dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 4-6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether nightly fasting combined with the diabetes drug metformin can slow breast cancer growth. Researchers aim to determine if this combination can prevent invasive breast cancer or ductal carcinoma in situ, a non-invasive type of cancer. Women diagnosed with certain types of operable breast cancer who are not receiving chemotherapy before surgery may qualify for this study. Participants will fast for at least 16 hours each night and use a device to monitor blood sugar levels. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking findings.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are using oral hormonal contraceptives, female hormones, topiramate, or other carbonic anhydrase inhibitors. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that metformin, a common medication for type II diabetes, may also protect against cancer. People with diabetes who take metformin tend to have a lower risk of developing cancer and a better chance of surviving it. In women with breast cancer, metformin has been linked to fewer cancer cells and improved outcomes.

Regarding nightly fasting, studies suggest it might lower cancer risk and improve treatment results. Some research indicates that women who fast longer at night have a reduced risk of breast cancer recurrence. Fasting may also enhance chemotherapy's effectiveness and reduce its side effects.

Overall, both metformin and nightly fasting have demonstrated benefits in past research. They are generally well-tolerated, but discussing any potential side effects or risks with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it combines metformin, a medication traditionally used to manage diabetes, with nightly fasting, offering a novel approach to breast cancer treatment. Unlike standard therapies like chemotherapy or hormone treatments, this method aims to harness the metabolic effects of fasting and metformin to potentially slow cancer growth. By incorporating continuous glucose monitoring, the trial provides valuable insights into how these interventions might influence cancer metabolism. This innovative approach could open new doors for managing breast cancer by targeting the disease through metabolic pathways, rather than the more conventional methods that focus on directly attacking cancer cells.

What evidence suggests that the combination of metformin and nightly fasting might be an effective treatment for breast cancer?

Research shows that metformin, which participants in this trial may receive, might help slow the growth of cancer cells. Studies have found that people with diabetes who take metformin have a lower risk of developing certain cancers, such as breast cancer. Specifically, one study found that people using metformin had a 90.4% chance of remaining cancer-free for five years, compared to 85.4% for those not using it.

Research also suggests that fasting overnight, another component of this trial, could reduce cancer risk and improve outcomes. Women who fasted for less than 13 hours each night had a higher chance of breast cancer returning compared to those who fasted longer. Fasting may also lower inflammation, which is linked to a reduced risk of breast cancer. Together, metformin and fasting, as studied in this trial, show promise in slowing breast cancer growth. ^{1 2 4 5 6}

Who Is on the Research Team?

Parijatham Thomas, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for women over 18 with early-stage breast cancer (ER+ve and/or PgR+ve) who are fit for surgery but not receiving neoadjuvant therapy. They must have normal organ function, no prior breast cancer treatment, and agree to use contraception. Excluded are those with serious illnesses, low BMI, diabetes or glucose intolerance, metformin allergies, current investigational drug use, recent hormone treatments excluding IUDs/vaginal creams, pregnant/breastfeeding women, intermittent fasters.

Inclusion Criteria

Your creatinine levels are within the normal range for the hospital or clinic where you are being treated.

My kidneys are functioning well enough to clear waste.

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Pregnant women should not go without eating for a long time.

I do not have someone to help me if needed.

My BMI is under 18.5.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants fast for >= 16 hours every night and use the continuous glucose monitoring system for 4-6 weeks. They receive nutritional counseling and metformin hydrochloride extended release until the day of surgery.

4-6 weeks

2 visits (in-person) for counseling, continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including the collection of blood and tissue samples.

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Metformin Hydrochloride Extended Release
• Nightly Fasting

Trial Overview The study examines the effects of extended nightly fasting combined with a diabetes medication called extended-release Metformin on reducing breast tumor growth in women at risk for or diagnosed with early-stage breast cancer. It aims to see if this combination can decrease cell proliferation without causing weight loss.

How Is the Trial Designed?

Group I: Arm I (fasting, glucose monitoring, counseling, metformin) Experimental Treatment 5 Interventions

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).

Group II: Arm II (glucose monitoring) Active Control 2 Interventions

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).

Metformin Hydrochloride Extended Release is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes mellitus

Approved in United States as Glucophage for:

• Type 2 diabetes mellitus

Approved in Canada as Glucophage for:

• Type 2 diabetes mellitus

Approved in Japan as Glucophage for:

• Type 2 diabetes mellitus

Approved in China as Glucophage for:

• Type 2 diabetes mellitus

Approved in Switzerland as Glucophage for:

• Type 2 diabetes mellitus

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study involving 349 patients with Type 2 diabetes, the combination of insulin glargine and glimepiride was found to be safe and effective for managing blood sugar levels during Ramadan fasting, with only one severe hypoglycaemic episode reported in each time period.

Mild hypoglycaemic episodes increased significantly during Ramadan, but the risk was higher in patients with lower body weight and waist circumference, suggesting that careful monitoring and adjustments in medication are necessary for safe fasting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of insulin glargine and glimepiride in subjects with Type 2 diabetes before, during and after the period of fasting in Ramadan. Salti, I.[2022]

Periodic fasting enhances the effectiveness of endocrine treatments for hormone receptor-positive breast cancer by increasing their anti-cancer activity.

Fasting may help delay the development of resistance to these treatments by lowering levels of blood leptin, insulin, and insulin-like growth factor 1 (IGF1), suggesting a potential new strategy for improving breast cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing endocrine therapy activity via fasting cycles: biological rationale and clinical feasibility. Caffa, I., Nencioni, A.[2021]

In a study of 254 patients with type 2 diabetes fasting during Ramadan, vildagliptin significantly reduced the risk of hypoglycemic events compared to sulfonylureas (1.7% vs. 19.2%), highlighting its safety profile during fasting.

Vildagliptin also demonstrated better glycemic control, with a mean HbA1c change of -0.1% compared to +0.3% for sulfonylureas, and resulted in a modest weight loss, making it a favorable option for managing diabetes in fasting patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Vildagliptin Versus Sulfonylurea in Muslim Patients with Type 2 Diabetes Fasting During Ramadan in Egypt: Results from VIRTUE Study. Khattab, M., Mahmoud, K., Shaltout, I.[2020]

Time-restricted eating (TRE) appears to be safe for individuals with type 2 diabetes, based on four completed studies and 14 ongoing studies, provided that their antidiabetic medications are monitored and adjusted accordingly.

Despite the promising safety profile of TRE, the limited number of studies and their low generalizability highlight the need for further research to establish clear recommendations for its efficacy and safety in managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Time-Restricted Eating Safe in the Treatment of Type 2 Diabetes?-A Review of Intervention Studies. Uldal, S., Clemmensen, KKB., Persson, F., et al.[2022]

Short-term fasting (STF) was well tolerated by patients undergoing chemotherapy for early breast cancer and resulted in significantly higher erythrocyte and thrombocyte counts post-treatment compared to those who did not fast.

STF may help reduce DNA damage in peripheral blood mononuclear cells after chemotherapy, suggesting a protective effect against some of the harmful side effects of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study. de Groot, S., Vreeswijk, MP., Welters, MJ., et al.[2021]

Preliminary findings indicate that combining intermittent fasting or a fasting-mimicking diet with endocrine therapy may enhance the effectiveness of treatment for hormone receptor-positive breast cancer.

This combination approach could also help in reducing side effects associated with the endocrine therapy, suggesting a potential strategy for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fasting May Complement Endocrine Therapy. [2021]

Periodic fasting or a fasting-mimicking diet enhances the effectiveness of endocrine therapies like tamoxifen and fulvestrant in hormone-receptor-positive breast cancer by lowering levels of IGF1, insulin, and leptin, and inhibiting cancer-related signaling pathways.

In mouse models, combining a fasting-mimicking diet with fulvestrant and palbociclib led to significant tumor regression and overcame drug resistance, while in patients, similar metabolic changes were observed, suggesting potential benefits for clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fasting-mimicking diet and hormone therapy induce breast cancer regression. Caffa, I., Spagnolo, V., Vernieri, C., et al.[2022]

In a 24-week study involving 493 participants, Empagliflozin significantly reduced HbA1c levels and body weight in patients with type 2 diabetes mellitus (T2DM) during Ramadan fasting, demonstrating its efficacy.

The use of Empagliflozin did not increase the risk of hypoglycemia or dehydration compared to the control group, indicating it is a safe option for managing T2DM during fasting periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Empagliflozin in Patients with Type 2 Diabetes Mellitus Fasting During Ramadan: A Real-World Study from Bangladesh. Pathan, MDF., Akter, N., Selim, S., et al.[2023]

In a study involving adults with type 2 diabetes fasting during Ramadan, liraglutide (1.8 mg) showed similar glycaemic control compared to sulphonylurea when combined with metformin, with no significant difference in fructosamine levels between the two groups.

Liraglutide treatment resulted in fewer hypoglycaemic episodes and a greater reduction in body weight compared to sulphonylurea, indicating it is a safe and effective option for managing diabetes during fasting periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of liraglutide compared to sulphonylurea during Ramadan in patients with type 2 diabetes (LIRA-Ramadan): a randomized trial. Azar, ST., Echtay, A., Wan Bebakar, WM., et al.[2022]

Fasting for up to 5 days may protect cancer patients undergoing chemotherapy by significantly reducing glucose and IGF-I levels, potentially enhancing the body's natural defenses without causing chronic weight loss.

In contrast to long-term calorie restriction, which requires weeks to show effects and can lead to weight loss, fasting offers a quicker and more effective way to improve treatment outcomes for cancer patients, suggesting it could be a valuable clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients. Lee, C., Longo, VD.[2011]

Intermittent fasting can lower glucose levels in tumors, making them more responsive to the cancer drug metformin.

The study shows that using intermittent fasting before metformin treatment not only sensitizes resistant tumor cells but also significantly reduces tumor growth, suggesting a potential new strategy for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teaching an Old Drug New Tricks. Momcilovic, M., Shackelford, DB.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4200668/

Metformin in cancer prevention and therapy - PMC The results of preclinical studies undoubtedly confirm the efficacy of metformin to inhibit cancer cell growth in vitro and to reduce tumor spread in animal ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06763328

Study Details | NCT06763328 | Metformin for the Treatment ... To determine if extended release metformin hydrochloride (metformin) can normalize glycosylated hemoglobin (HgbA1c) (< 5.7%) for women breast cancer survivors ...

3. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04263-8

Metformin and cancer hallmarks: shedding new lights on ... Epidemiological studies have revealed that metformin exerts protective effects on people with diabetes suffering from cancer [10,11,12].

4. sciencedirect.com sciencedirect.com/science/article/pii/S1043661824003128

Metformin: From diabetes to cancer to prolongation of life Metformin use has been shown to reduce the frequency of specific cancers, in particular breast cancer [141] and to be an effective radiosensitizer in the ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4303170/

The effect of metformin on breast cancer outcomes in ... Five-year RFS was 90.4% (95% CI, 84–97) in metformin users and 85.4% (95% CI, 78–94) in nonusers. In this cohort of patients with type 2 diabetes receiving ...

6. mdpi.com mdpi.com/1422-0067/25/7/4083

Metformin: A Dual-Role Player in Cancer Treatment and ... Diabetic patients on metformin not only exhibited a reduced incidence of cancer but also demonstrated lower all-cause mortality [147,148]. For instance, there ...