Metformin + Fasting for Breast Cancer
Recruiting in Palo Alto (17 mi)
+2 other locations
Overseen byAndrea De Censi
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
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.
What data supports the idea that Metformin + Fasting for Breast Cancer is an effective treatment?
The available research shows that combining fasting with treatments for hormone-receptor-positive breast cancer can enhance their effectiveness. For example, fasting increases the activity of drugs like tamoxifen and fulvestrant, which are used to treat this type of breast cancer. It does this by lowering certain hormones and proteins in the blood, like insulin and IGF1, which are linked to cancer growth. Additionally, fasting helps prevent some side effects of these treatments. Another study found that intermittent fasting can make tumors more sensitive to metformin, a drug that reduces tumor growth. These findings suggest that fasting, when combined with certain breast cancer treatments, can improve their effectiveness and reduce side effects.
12345What safety data exists for Metformin and fasting in breast cancer treatment?
The research provided does not directly address the safety of Metformin combined with fasting for breast cancer treatment. However, it includes studies on time-restricted eating (TRE) and Metformin in the context of type 2 diabetes. These studies suggest that TRE is generally safe for people with type 2 diabetes when medication is monitored and adjusted. Metformin is commonly used in these contexts, indicating it is generally considered safe with fasting in diabetes management. More specific studies are needed to determine the safety of this combination for breast cancer treatment.
678910Is Metformin Hydrochloride Extended Release with Nightly Fasting a promising treatment for breast cancer?
Yes, combining Metformin with nightly fasting shows promise for breast cancer treatment. Research suggests that fasting can enhance the effectiveness of cancer drugs like Metformin by making cancer cells more sensitive to treatment and reducing tumor growth.
123511Eligibility Criteria
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
I am 18 years old or older.
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.
+10 more
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.
+17 more
Trial Timeline
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)
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm I (fasting, glucose monitoring, counseling, metformin)Experimental Treatment5 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 Control2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Enhancing endocrine therapy activity via fasting cycles: biological rationale and clinical feasibility. [2021]We found that periodic fasting increases the anti-cancer activity of endocrine agents used to treat hormone receptor-positive breast cancer and delays acquired resistance to them by reducing blood leptin, insulin and insulin-like growth factor 1 (IGF1). Our work supports further clinical studies of fasting as an adjuvant to endocrine agents in breast cancer patients.
Fasting-mimicking diet and hormone therapy induce breast cancer regression. [2022]Approximately 75% of all breast cancers express the oestrogen and/or progesterone receptors. Endocrine therapy is usually effective in these hormone-receptor-positive tumours, but primary and acquired resistance limits its long-term benefit1,2. Here we show that in mouse models of hormone-receptor-positive breast cancer, periodic fasting or a fasting-mimicking diet3-5 enhances the activity of the endocrine therapeutics tamoxifen and fulvestrant by lowering circulating IGF1, insulin and leptin and by inhibiting AKT-mTOR signalling via upregulation of EGR1 and PTEN. When fulvestrant is combined with palbociclib (a cyclin-dependent kinase 4/6 inhibitor), adding periodic cycles of a fasting-mimicking diet promotes long-lasting tumour regression and reverts acquired resistance to drug treatment. Moreover, both fasting and a fasting-mimicking diet prevent tamoxifen-induced endometrial hyperplasia. In patients with hormone-receptor-positive breast cancer receiving oestrogen therapy, cycles of a fasting-mimicking diet cause metabolic changes analogous to those observed in mice, including reduced levels of insulin, leptin and IGF1, with the last two remaining low for extended periods. In mice, these long-lasting effects are associated with long-term anti-cancer activity. These results support further clinical studies of a fasting-mimicking diet as an adjuvant to oestrogen therapy in hormone-receptor-positive breast cancer.
Teaching an Old Drug New Tricks. [2020]In this issue of Cancer Cell, Elgendy et al. describe the use of intermittent fasting as a strategy to reduce tumor glucose levels and sensitize otherwise resistant tumor cells to metformin. The authors demonstrate that intermittent fasting before metformin treatment sensitized tumors to metformin and significantly reduced tumor growth.
Fasting May Complement Endocrine Therapy. [2021]Preliminary findings from a recent study suggest that combining intermittent fasting or a fasting-mimicking diet with endocrine therapy for hormone receptor-positive breast cancer may improve treatment efficacy and reduce side effects.
The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study. [2021]Preclinical evidence shows that short-term fasting (STF) protects healthy cells against side effects of chemotherapy and makes cancer cells more vulnerable to it. This pilot study examines the feasibility of STF and its effects on tolerance of chemotherapy in a homogeneous patient group with early breast cancer (BC).
Efficacy and safety of liraglutide compared to sulphonylurea during Ramadan in patients with type 2 diabetes (LIRA-Ramadan): a randomized trial. [2022]Compare effects of liraglutide 1.8 mg and sulphonylurea, both combined with metformin, on glycaemic control in patients with type 2 diabetes (T2D) fasting during Ramadan.
Is Time-Restricted Eating Safe in the Treatment of Type 2 Diabetes?-A Review of Intervention Studies. [2022]Time-restricted eating (TRE) has been shown to improve body weight and glucose metabolism in people at high risk of type 2 diabetes. However, the safety of TRE in the treatment of type 2 diabetes is unclear. We investigated the safety of TRE interventions in people with type 2 diabetes by identifying published and ongoing studies. Moreover, we identified the commonly used antidiabetic drugs and discussed the safety of TRE in people with type 2 diabetes considering the use of these drugs. In addition, we addressed the research needed before TRE can be recommended in the treatment of type 2 diabetes. A literature search was conducted to identify published (MEDLINE PubMed) and ongoing studies (ClinicalTrials.gov) on TRE in people with type 2 diabetes. To assess the usage of antidiabetic drugs and to discuss pharmacodynamics and pharmacokinetics in a TRE context, the most used antidiabetic drugs were identified and analysed. Statistics regarding sale of pharmaceuticals were obtained from MEDSTAT.DK which are based on data from the national Register of Medicinal Product Statistics, and from published studies on medication use in different countries. Four published studies investigating TRE in people with type 2 diabetes were identified as well as 14 ongoing studies. The completed studies suggested that TRE is safe among people with type 2 diabetes. Common antidiabetic drugs between 2010 and 2019 were metformin, insulin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, sulfonylureas, and sodium-glucose cotransporter-2 inhibitors. Existing studies suggest that TRE is not associated with major safety issues in people with type 2 diabetes as long as medication is monitored and adjusted. However, because of low generalisability of the few studies available, more studies are needed to make concrete recommendations regarding efficacy and safety of TRE in people with type 2 diabetes.
Efficacy and safety of insulin glargine and glimepiride in subjects with Type 2 diabetes before, during and after the period of fasting in Ramadan. [2022]To determine the safety and efficacy of insulin glargine and glimepiride in patients with Type 2 diabetes before and after Ramadan and during fasting for Ramadan.
Efficacy and Safety of Empagliflozin in Patients with Type 2 Diabetes Mellitus Fasting During Ramadan: A Real-World Study from Bangladesh. [2023]In Bangladesh, there is a large population of Muslims with type 2 diabetes mellitus (T2DM) who fast during Ramadan. Changes in the pattern of meal and fluid intake during this long-fasting hours may increase the risk of hypoglycaemia, hyperglycaemia, and dehydration. Our key point of focus was to evaluate the efficacy and safety of Empagliflozin, a sodium-glucose co transporter 2 inhibitor (SGLT2i), in patients with T2DM while fasting during Ramadan.
Effect of Vildagliptin Versus Sulfonylurea in Muslim Patients with Type 2 Diabetes Fasting During Ramadan in Egypt: Results from VIRTUE Study. [2020]Fasting in patients with type 2 diabetes mellitus (T2DM) is associated with high risk of hypoglycemia. The aim of this study was to compare the effectiveness and safety of vildagliptin in T2DM patients fasting during Ramadan in a real-life setting in Egypt.
Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients. [2011]The dietary recommendation for cancer patients receiving chemotherapy, as described by the American Cancer Society, is to increase calorie and protein intake. Yet, in simple organisms, mice, and humans, fasting--no calorie intake--induces a wide range of changes associated with cellular protection, which would be difficult to achieve even with a cocktail of potent drugs. In mammals, the protective effect of fasting is mediated, in part, by an over 50% reduction in glucose and insulin-like growth factor 1 (IGF-I) levels. Because proto-oncogenes function as key negative regulators of the protective changes induced by fasting, cells expressing oncogenes, and therefore the great majority of cancer cells, should not respond to the protective signals generated by fasting, promoting the differential protection (differential stress resistance) of normal and cancer cells. Preliminary reports indicate that fasting for up to 5 days followed by a normal diet, may also protect patients against chemotherapy without causing chronic weight loss. By contrast, the long-term 20 to 40% restriction in calorie intake (dietary restriction, DR), whose effects on cancer progression have been studied extensively for decades, requires weeks-months to be effective, causes much more modest changes in glucose and/or IGF-I levels, and promotes chronic weight loss in both rodents and humans. In this study, we review the basic as well as clinical studies on fasting, cellular protection and chemotherapy resistance, and compare them to those on DR and cancer treatment. Although additional pre-clinical and clinical studies are necessary, fasting has the potential to be translated into effective clinical interventions for the protection of patients and the improvement of therapeutic index.