Metformin and Remote Monitoring for Brain Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Metformin, Resveratrol, CoQ10, others

Disqualifiers: Pregnancy, Nursing, Imprisonment, 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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: 12 months

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial evaluates whether patient care can be done remotely for patients having cranial (skull) radiation or who have previously had cranial radiation. In addition, this trial compares study outcomes between patients who get metformin and those who do not. Cranial radiation, an essential component of brain tumor treatment, can result in significant negative effects on cognitive (the ability to clearly think, learn, and remember) function. Wearable devices have been used in the field of neurology for seizure detection and assessment of patients with movement disorders. Wearable device technology has also been implemented for remote monitoring of cancer patients and for cancer clinical trials. Metformin is the active ingredient in a drug used to treat type 2 diabetes mellitus (a condition in which the body cannot control the level of sugar in the blood). It is also being studied in the treatment of cancer. Use of metformin may reduce risk of cognitive decline following radiation therapy within the skull (intracranial). These effects may be further strengthen by addition of device-based physical activity promotion. Mayo Test Drive is a web-based platform for remote self-administered cognitive assessment. Using Mayo Test Drive may help determine whether patient care can be done remotely, while simultaneously evaluating benefits of health promotion through use of a wearable watch device and metformin in preventing radiation-related cognitive decline.

Will I have to stop taking my current medications?

The trial requires you to stop taking resveratrol, CoQ10, coconut oil, and curcumin supplements before joining and remain off them during the study. If you are currently taking metformin, you must be able to safely stop if assigned to the control group.

What data supports the effectiveness of the drug metformin for brain cancer?

Some studies suggest that metformin, a drug commonly used to treat diabetes, might help reduce cancer progression, but its effectiveness in improving survival for brain cancer patients, specifically glioblastoma, is not clearly proven. More research is needed to understand if metformin can benefit certain patients with specific tumor characteristics. ^{1 2 3 4 5}

Is metformin safe for use in brain cancer treatment?

Metformin, commonly used for diabetes, has been tested in brain cancer patients and is generally well tolerated. In a study, doses up to 2250 mg/day were used without serious side effects, with common issues like appetite loss, nausea, and diarrhea being manageable. ^{1 2 4 5 6}

How does the drug metformin differ from other treatments for brain cancer?

Metformin, commonly used for diabetes, is being explored for brain cancer due to its potential to limit energy supply to tumor cells, which might slow cancer progression. Unlike standard treatments, metformin's unique approach targets the metabolism of cancer cells, although its effectiveness in improving survival for glioblastoma patients is still under investigation. ^{1 2 5 7 8}

Research Team

Ugur T. Sener, MD

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for patients who have had cranial radiation therapy due to brain cancer or tumors. It's designed to see if care can be managed remotely using a web platform and wearable devices, and whether metformin helps prevent cognitive decline post-radiation.

Inclusion Criteria

Ability to complete cognitive assessments and questionnaires by themselves or with assistance

I am mostly active and can care for myself, with a KPS score of 70 or more.

Expected survival ≥ 6 months in the opinion of treatment team

Exclusion Criteria

I do not have any health issues that would make it unsafe for me to join the study.

I am not pregnant, nursing, imprisoned, or unable to understand my condition.

Known hypersensitivity or allergy to metformin

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metformin or standard of care treatment for 12 months, with wearable device monitoring and neurocognitive tests

12 months

Monthly remote assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Follow-up at 30 days, then every 3 months

Treatment Details

Interventions

• Metformin

Trial Overview The study tests remote patient care via the Mayo Test Drive platform and monitors physical activity with wearable devices. It also examines if metformin reduces cognitive issues after skull radiation compared to those not taking it.

Participant Groups

Group I: Group A (metformin) Experimental Treatment 4 Interventions

Patients receive metformin PO BID for 12 months. Treatment repeats every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also wear a wearable device to monitor health and undergo neurocognitive test throughout the study.

Group II: Group B (usual care) Active Control 4 Interventions

Patients receive SOC treatment for 12 months. Patients also wear a wearable device to monitor health and undergo neurocognitive test throughout the study.

Metformin 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

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

In a pooled analysis of 1,731 glioblastoma patients from three clinical trials, metformin use was not significantly associated with improved overall survival (OS) or progression-free survival (PFS) during or after treatment with radiochemotherapy.

While there was a nonsignificant trend suggesting potential benefits of metformin monotherapy at baseline, this effect was not observed during concurrent treatment with temozolomide and radiotherapy, indicating that metformin does not prolong survival in newly diagnosed glioblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of metformin and outcome of patients with newly diagnosed glioblastoma: Pooled analysis. Seliger, C., Genbrugge, E., Gorlia, T., et al.[2020]

In a study of 276 glioblastoma patients, persistent high blood sugar levels and corticosteroid therapy were linked to lower survival rates, highlighting their negative impact on patient outcomes.

Diabetic patients treated with metformin showed longer progression-free survival, suggesting that metformin may have a beneficial effect in managing glioblastoma, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin influences progression in diabetic glioblastoma patients. Adeberg, S., Bernhardt, D., Ben Harrabi, S., et al.[2022]

Current evidence suggests that metformin, an oral antidiabetic drug, may have beneficial effects when used alongside chemotherapy for brain cancer treatment, particularly gliomas.

Further research is necessary to fully understand the relationship between diabetes, metabolism, and cancer, as brain tumors have a high mortality rate despite existing treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic pharmacology: a link between metabolic syndrome and neuro-oncology? Aldea, M., Tomuleasa, C., Petrushev, B., et al.[2017]

In a phase II clinical trial involving 81 patients with recurrent or refractory glioblastoma, the combination of metformin and low-dose temozolomide was well tolerated but did not show a significant clinical benefit in terms of progression-free survival or overall survival compared to the control group receiving placebo and temozolomide.

The median overall survival was 17.22 months for the metformin group versus 7.69 months for the control group, but this difference was not statistically significant, indicating that metformin may not improve outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study). Yoon, WS., Chang, JH., Kim, JH., et al.[2023]

Metformin (MET) significantly reduces the viability and proliferation of glioblastoma endothelial cells, promoting apoptosis through increased activity of caspases 3/7, indicating its potential as a therapeutic agent against this aggressive brain cancer.

MET also decreases angiogenesis and invasiveness in glioblastoma cells by altering sphingolipid metabolism, suggesting it could be safely repurposed as an add-on therapy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Metformin as Add-On Therapy against Glioblastoma: An Old Medicine for Novel Oncology Therapeutics. Guarnaccia, L., Navone, SE., Masseroli, MM., et al.[2022]

In a phase I/II study involving patients with newly diagnosed glioblastoma, metformin (MF) was well tolerated at doses up to 2250 mg/day when combined with maintenance temozolomide (TMZ), with no dose-limiting toxicities observed.

The study showed that while some patients experienced tumor progression, five out of eight patients remained stable, suggesting potential benefits of MF in managing glioblastoma after standard therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin with Temozolomide for Newly Diagnosed Glioblastoma: Results of Phase I Study and a Brief Review of Relevant Studies. Ohno, M., Kitanaka, C., Miyakita, Y., et al.[2022]

Metformin, an anti-diabetic drug, was found to decrease cell survival in glioblastoma multiforme (GBM) cells and reduce the expression of certain microRNAs associated with tumor aggressiveness, suggesting its potential as a therapeutic agent against GBM.

The study showed that metformin increased the expression of proteins involved in exosome biogenesis and secretion, indicating that it may enhance the release of exosomes from GBM cells, which could influence tumor behavior and treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin Increases Exosome Biogenesis and Secretion in U87 MG Human Glioblastoma Cells: A Possible Mechanism of Therapeutic Resistance. Soraya, H., Sani, NA., Jabbari, N., et al.[2021]

In a study of 241 glioblastoma patients, metformin use was linked to longer overall survival, particularly in those with tumors that had a methylated MGMT promoter, showing a survival time of 484 days compared to 394 days for non-users.

Cox regression analysis indicated that metformin significantly reduced the risk of death at 2 years for patients with methylated MGMT promoters, suggesting it may be an effective adjunct treatment for this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin use is associated with longer survival in glioblastoma patients with MGMT gene silencing. Mohammad, AH., Jatana, S., Ruiz-Barerra, MA., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Use of metformin and outcome of patients with newly diagnosed glioblastoma: Pooled analysis. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

Metformin influences progression in diabetic glioblastoma patients. [2022]

3. Cyprus pubmed.ncbi.nlm.nih.gov

Antidiabetic pharmacology: a link between metabolic syndrome and neuro-oncology? [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study). [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Metformin as Add-On Therapy against Glioblastoma: An Old Medicine for Novel Oncology Therapeutics. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Metformin with Temozolomide for Newly Diagnosed Glioblastoma: Results of Phase I Study and a Brief Review of Relevant Studies. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Metformin Increases Exosome Biogenesis and Secretion in U87 MG Human Glioblastoma Cells: A Possible Mechanism of Therapeutic Resistance. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Metformin use is associated with longer survival in glioblastoma patients with MGMT gene silencing. [2023]