Metformin for Prostate Cancer and Metabolic Syndrome

(PRIME Trial)

Recruiting at 15 trial locations

Overseen By Leanne Chiu, BA

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Canadian Urologic Oncology Group

Must be taking: LHRH agonist/antagonist

Must not be taking: Metformin, diabetic medications

Disqualifiers: Diabetes, Liver disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

168 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking metformin or other diabetic medications, or have taken them within 28 days before joining the trial.

What data supports the effectiveness of the drug Metformin for prostate cancer?

Some studies suggest that Metformin might have beneficial effects on prostate cancer by potentially reducing the development of more aggressive forms of the disease. However, other research indicates that Metformin use does not significantly lower the risk of being diagnosed with prostate cancer. ^{1 2 3 4 5}

Is metformin safe for humans?

Metformin, a medication commonly used for type 2 diabetes, has been studied for its safety in humans and is generally considered safe. It has been used for many years and is well-tolerated by most people, though it can have side effects like stomach upset and diarrhea. ^{2 3 6 7 8}

How does the drug Metformin differ from other treatments for prostate cancer and metabolic syndrome?

Metformin is unique because it may help reduce prostate cancer risk by lowering high insulin levels and directly affecting cancer cells, which is different from traditional prostate cancer treatments that primarily focus on hormone levels or chemotherapy. ^{2 5 8 9 10}

What is the purpose of this trial?

This trial tests if metformin can help men with advanced prostate cancer on ADT by reducing the risk and severity of metabolic syndrome. Metformin helps control blood sugar by improving how the body uses insulin. Metformin is the most used drug for type 2 diabetes and has shown potential anti-cancer effects in various studies.

Research Team

Bernie Eigl, MD

Principal Investigator

British Columbia Cancer Agency

Nawaid Usmani, MD

Principal Investigator

University of Alberta

Eligibility Criteria

Inclusion Criteria

You have been receiving ongoing treatment for localized prostate cancer for at least 9 months, have metastatic disease, or have an increasing PSA level after previous surgery for prostate cancer.

Your PSA level is higher than 2ng/mL after receiving radiotherapy.

If you are receiving androgen deprivation therapy, you must have already decided if you will take it continuously or with breaks before joining the study.

Exclusion Criteria

You have not received hormone therapy for prostate cancer within the last year, unless you started it within the last 45 days before starting the study.

You have been diagnosed with diabetes according to the Canadian Diabetes Association criteria within 28 days before enrolling in the study.

You have a history of lactic acidosis or conditions that make you more likely to develop lactic acidosis, like kidney problems, liver disease, alcohol abuse, severe infection, or heart failure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metformin or placebo alongside androgen deprivation therapy for 18 months

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term follow-up

Participants are assessed for overall survival and other long-term outcomes

36 months

Treatment Details

Interventions

• Metformin
• Placebo Oral Tablet

Participant Groups

Group I: Metformin Experimental Treatment 1 Intervention

Metformin 850 mg PO OD X 30 days, then 850mg PO BID for a total of 18 months

Group II: Placebo Placebo Group 1 Intervention

Placebo Oral Tablet 1 tablet (850mg) PO OD X 30 days, then 850mg PO BID for a total of 18 months

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?

Canadian Urologic Oncology Group

Lead Sponsor

Trials

8

Recruited

920+

BC Cancer Foundation

Collaborator

Trials

20

Recruited

8,600+

British Columbia Cancer Agency

Collaborator

Trials

181

Recruited

95,900+

Prostate Cancer Canada

Collaborator

Trials

10

Recruited

7,500+

Findings from Research

In a study of 2901 prostate cancer patients, those using metformin showed significantly better clinical outcomes, including improved prostate cancer-specific mortality (PCSM) and reduced risk of developing castration-resistant prostate cancer (CRPC) compared to diabetic patients not using metformin.

Metformin use was associated with a nearly doubled rate of prostate-specific antigen-recurrence-free survival (PSA-RFS) and a more than threefold increase in distant metastases-free survival (DMFS), suggesting its potential as a beneficial treatment in localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin and prostate cancer: reduced development of castration-resistant disease and prostate cancer mortality. Spratt, DE., Zhang, C., Zumsteg, ZS., et al.[2022]

The novel biguanide derivative IM176 significantly reduced the viability of prostate cancer cell lines and patient-derived castration-resistant prostate cancer (CRPC) cells, showing lower IC50 values than metformin and phenformin, indicating it may be more effective in treating these cancers.

IM176 activates AMP-activated protein kinase, inhibits the mammalian target of rapamycin (mTOR), and induces apoptosis in prostate cancer cells, suggesting a strong mechanism of action that could make it a promising candidate for prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel biguanide derivative, IM176, induces prostate cancer cell death by modulating the AMPK-mTOR and androgen receptor signaling pathways. Kim, Y., Yoo, S., Lim, B., et al.[2023]

In a study of 6689 prostate cancer patients, those with preexisting type 2 diabetes mellitus (T2DM) had a higher overall mortality risk, but there was no significant difference in prostate cancer-specific survival between diabetic and non-diabetic patients.

Patients with T2DM who were not treated with metformin had a notably lower overall survival rate, while those on metformin showed a trend towards lower prostate cancer-specific mortality, suggesting potential benefits of metformin in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preexisting diabetes, metformin use and long-term survival in patients with prostate cancer. Linkeviciute-Ulinskiene, D., Patasius, A., Kincius, M., et al.[2022]

In a study of 25,695 male patients with type 2 diabetes, metformin users had a 20% lower risk of developing new-onset prostate cancer compared to those using sulfonylureas, indicating a potential protective effect of metformin.

Metformin was also associated with a 11% reduction in all-cause mortality compared to sulfonylurea users, suggesting that it may offer additional health benefits beyond blood sugar control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of New-Onset Prostate Cancer for Metformin Versus Sulfonylurea Use in Type 2 Diabetes Mellitus: A Propensity Score-Matched Study. Lee, YHA., Zhou, J., Hui, JMH., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Metformin and prostate cancer: reduced development of castration-resistant disease and prostate cancer mortality. [2022]

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

Metformin use and risk of prostate cancer: results from the REDUCE study. [2018]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

A novel biguanide derivative, IM176, induces prostate cancer cell death by modulating the AMPK-mTOR and androgen receptor signaling pathways. [2023]

4. Sweden pubmed.ncbi.nlm.nih.gov

Preexisting diabetes, metformin use and long-term survival in patients with prostate cancer. [2022]

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

Metformin use and prostate cancer risk. [2014]

6. Sweden pubmed.ncbi.nlm.nih.gov

Antidiabetic drug use and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer. [2017]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study. [2022]

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

Risk of New-Onset Prostate Cancer for Metformin Versus Sulfonylurea Use in Type 2 Diabetes Mellitus: A Propensity Score-Matched Study. [2022]

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

Impact of Addition of Metformin to Abiraterone in Metastatic Castration-Resistant Prostate Cancer Patients With Disease Progressing While Receiving Abiraterone Treatment (MetAb-Pro): Phase 2 Pilot Study. [2020]

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

Metabolic syndrome as a peculiar target for management of prostate cancer patients. [2022]