Metformin for Prostate Cancer and Metabolic Syndrome

(PRIME Trial)

No longer recruiting at 16 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether metformin, a common diabetes medication, can help treat advanced prostate cancer when combined with standard hormone therapy (androgen deprivation therapy or ADT). The goal is to determine if metformin improves treatment outcomes compared to a placebo (a non-active pill). The study seeks men with advanced prostate cancer who are starting or have just started hormone therapy. Participants should not have diabetes or be taking metformin already. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that metformin is generally safe for most people. Often used to treat diabetes, it has also been studied for its effects on prostate cancer. Studies suggest that metformin might help patients with prostate cancer live longer and reduce some treatment-related issues.

While metformin is usually safe, some people might experience mild side effects like an upset stomach or diarrhea. These side effects are typically temporary and manageable. Since this trial is in a late stage, metformin's safety has been thoroughly studied, providing confidence in its safety for this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Metformin is unique because it is primarily known as a diabetes medication, but researchers are exploring its potential to combat prostate cancer and metabolic syndrome. Unlike traditional prostate cancer treatments like hormone therapy or chemotherapy, Metformin works by targeting metabolic pathways, potentially slowing cancer growth. Its dual action of managing blood sugar levels and possibly inhibiting cancer cell proliferation makes it an exciting candidate for providing a more comprehensive treatment approach.

What evidence suggests that metformin might be an effective treatment for prostate cancer?

This trial will compare Metformin with a placebo to evaluate its effects on prostate cancer and metabolic syndrome. Research has shown that Metformin might benefit prostate cancer patients. Studies suggest it can improve outcomes such as PSA-RFS, which measures cancer recurrence, DMFS, which tracks time without cancer spreading, and overall survival. Metformin may also delay progression to a more resistant form of prostate cancer called CRPC. However, some studies found no additional anti-tumor effects when Metformin was added to standard treatments. Despite this, Metformin appears to offer metabolic benefits, helping with issues caused by androgen deprivation therapy, a common prostate cancer treatment. ^{1 4 6 7 8}

Who Is on the Research Team?

Bernie Eigl, MD

Principal Investigator

British Columbia Cancer Agency

Nawaid Usmani, MD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Metformin
• Placebo Oral Tablet

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4034673/

Metformin and Prostate Cancer: Benefit for Development of ...

To our knowledge, our results are the first clinical data to indicate that metformin use may improve PSA-RFS, DMFS, PCSM, OS, and reduce the development of CRPC ...

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0093775424000538

Efficacy of metformin drug in preventing metabolic ...

The efficacy of metformin in metabolic syndrome that resulted from using androgen deprivation therapy for prostate cancer patients was evaluated by the changes ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04925063

The Effect of Metformin in Patients With Newly Diagnosed ...

A prospective randomized study reported that metformin potentially lengthen time to CRPC in advanced prostate cancer patients when combined with ADT especially ...

4.

asco.org

asco.org/abstracts-presentations/ABSTRACT193754

Metformin to treat prostate cancer (PCa) and prevent ...

... metformin cohort. Conclusions: This study detected no impact of MET addition to ADT on the risk of metabolic syndrome and no additional anti-tumor effects.

5.

targetedonc.com

targetedonc.com/view/metformin-fails-to-improve-survival-in-metastatic-hormone-sensitive-prostate-cancer

Metformin Fails to Improve Survival in Metastatic Hormone ...

A recent trial reveals metformin does not enhance survival in metastatic prostate cancer but offers significant metabolic benefits during ...

6.

thelancet.com

thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00231-1/fulltext

Metformin for patients with metastatic prostate cancer ...

We hypothesised that metformin might improve survival in patients with metastatic hormone-sensitive prostate cancer and reduce metabolic ...

7.

auajournals.org

auajournals.org/doi/10.1097/JU.0000000000004695

A Randomized Phase 3 Trial of Metformin in Patients ...

We investigated whether metformin decreases metabolic syndrome (MS) risk in patients with prostate cancer (PCa) receiving androgen deprivation therapy (ADT) ...

8.

dmsjournal.biomedcentral.com

dmsjournal.biomedcentral.com/articles/10.1186/s13098-024-01397-7

Does metformin really reduce prostate cancer risk

In this study, we confirmed that no protective effect of metformin use on PCa risk. The association between metformin use and PCa risk reduction ...