SGLT2 Inhibition for High-Risk Prostate Cancer

Recruiting at 1 trial location

Overseen By Melissa A Reimers, M.D.

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: SGLT2i, Thiazolidinedione, Systemic steroids, others

Disqualifiers: Stroke, Type 1 diabetes, Severe kidney disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called dapagliflozin to determine its safety and effectiveness for individuals with certain types of high-risk prostate cancer before surgery. The goal is to assess whether dapagliflozin can shrink the tumor and be safely tolerated by patients. Suitable candidates for this trial have been diagnosed with prostate cancer classified as unfavorable intermediate, high-risk, or very high-risk and are planning prostate removal surgery. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking therapy.

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 using SGLT2 inhibitors, thiazolidinediones, or regularly scheduled systemic steroids like prednisone or dexamethasone.

Is there any evidence suggesting that dapagliflozin is likely to be safe for humans?

Research has shown that dapagliflozin, a drug commonly used for diabetes, might also be safe for treating prostate cancer. Studies have found that it can reduce the risk of prostate cancer by 23% in men. Most people tolerate it well, experiencing no serious side effects. This suggests dapagliflozin is safe enough to be tested for new uses, such as treating prostate cancer. So far, no major safety issues have been reported in those taking this medication for other conditions. ^{1 2 3 4 5}

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

Researchers are excited about Dapagliflozin for high-risk prostate cancer because it offers a novel approach compared to standard treatments like surgery, radiation, and hormone therapy. Unlike these options, Dapagliflozin is a type of SGLT2 inhibitor originally used for managing diabetes, which works by reducing glucose reabsorption in the kidneys. This distinct mechanism might help cut off the energy supply to cancer cells, potentially slowing cancer growth. Additionally, its oral administration makes it a convenient option for patients, setting it apart from the more invasive standard treatments.

What evidence suggests that dapagliflozin might be an effective treatment for high-risk prostate cancer?

Research suggests that dapagliflozin, a type of medication, might lower the risk of prostate cancer. One study found that this medication reduced the risk of prostate cancer by 23% in men. Another analysis also showed a significantly lower risk of prostate cancer with these medications, indicating possible benefits. In this trial, participants will receive dapagliflozin to evaluate its effects specifically in men at high risk for prostate cancer. Although direct evidence for dapagliflozin in this high-risk group is not yet available, these findings are encouraging. More research is needed to confirm its effectiveness for this particular condition. ^{1 2 3 4 6}

Who Is on the Research Team?

Melissa A Reimers, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Men over 18 with high-risk or very high risk localized prostate cancer, who are planning a radical prostatectomy and can undergo an MRI. They must have normal organ function and controlled type 2 diabetes (if diabetic). Exclusions include insulin-requiring diabetes, recent strokes, other active cancers, severe illnesses that could interfere with the study, or past use of certain diabetes drugs.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

My prostate cancer is classified as high or very high risk.

My prostate cancer is considered very high risk based on its stage or specific features.

Exclusion Criteria

You are currently taking any experimental drugs for other studies.

HbA1c > 10%, unless approved by endocrinologist.

I do not have any implants that would interfere with an MRI of my prostate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dapagliflozin at 10 mg by mouth once daily for 4 weeks prior to prostatectomy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BIOSENSE Meter
• Dapagliflozin

Trial Overview The trial is testing if taking Dapagliflozin daily for four weeks before surgery is safe and tolerable for patients with aggressive prostate cancer. The drug's effects will be monitored using a BIOSENSE Meter to ensure patient safety during the pre-surgery period.

How Is the Trial Designed?

Group I: Dapagliflozin Experimental Treatment 1 Intervention

* Dapagliflozin will be initiated once daily approximately 6 weeks prior to planned prostatectomy * Dapagliflozin will be given at 10 mg by mouth once daily for 4 weeks (days 1-28) prior to prostatectomy.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

The Foundation for Barnes-Jewish Hospital

Collaborator

Trials

43

Recruited

6,600+

Published Research Related to This Trial

Dapagliflozin effectively lowers blood sugar levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, with a low risk of hypoglycemia and additional benefits like weight loss and reduced blood pressure.

While it is generally safe, dapagliflozin can increase the risk of genital infections, particularly in women, and its efficacy may be reduced in patients with kidney issues; ongoing trials are investigating its potential cardiovascular and renal protective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes]. Scheen, AJ.[2021]

In a study of 552 patients (276 with diabetes mellitus and 276 without), diabetes did not negatively affect short-term overall survival rates in prostate cancer patients, with 5-year survival rates of 88% for those with diabetes compared to 93% for those without.

Prostate cancer and its treatment did not significantly impact glycemic control in patients with diabetes, indicating that having both conditions does not worsen health outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CO-EXISTING PROSTATE CANCER AND DIABETES MELLITUS: IMPLICATIONS FOR PATIENT OUTCOMES AND CARE. Karlin, NJ., Amin, SB., Verona, PM., et al.[2022]

In the REDUCE trial, which included mandatory biopsies for all participants, diabetes was not linked to a lower risk of prostate cancer (PCa), showing an odds ratio of 1.01, indicating equal risk for diabetic and non-diabetic men.

The study suggested that obesity may modify the relationship between diabetes and high-grade PCa, with diabetic normal-weight men having a decreased risk, while obese men showed an increased risk, highlighting the complex interaction between these factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes and prostate cancer risk in the REDUCE trial. Wu, C., Moreira, DM., Gerber, L., et al.[2011]

SGLT2 inhibitors effectively lower blood glucose levels in type 2 diabetes patients by increasing urinary glucose excretion, with reported reductions in fasting plasma glucose (FPG) by 14.4 to 45.8 mg/dL and HbA1c by 0.35 to 1.24%.

These medications are particularly beneficial for young, obese type 2 diabetics without renal impairment, but their effectiveness is reduced in patients with renal issues, making them more suitable as add-on therapy rather than first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mechanisms and efficacy of SGLT2 inhibitors]. Shiba, T.[2018]

SGLT2 inhibitors, like dapagliflozin, help lower blood sugar levels by increasing glucose excretion in urine, working independently of insulin, which is a unique mechanism among diabetes medications.

Clinical trials and real-life studies show that dapagliflozin not only improves glycemic control by reducing glycosylated hemoglobin but also contributes to weight loss and lower blood pressure, offering additional metabolic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Impact of dapagliflozin on cardiovascular risk factors. Beyond glycemic control]. Pallarés, V., Escobar, C., Egocheaga, I., et al.[2021]

In a study of 167 patients with both diabetes mellitus and prostate cancer, the use of antidiabetic drugs like metformin and insulin did not significantly affect prostate cancer aggressiveness or progression, as measured by Gleason scores and other clinical parameters.

However, tissue analysis indicated that metformin and insulin users had decreased activation of the mTOR pathway and changes in androgen receptor levels, suggesting that these drugs may influence tumor biology differently compared to those not using antidiabetic medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic drugs influence molecular mechanisms in prostate cancer. Pircher, A., Zieher, M., Eigentler, A., et al.[2020]

SGLT2 inhibitors are a new class of diabetes medications that work by blocking glucose reabsorption in the kidneys, leading to increased glucose excretion and lower blood sugar levels without relying on insulin.

The effectiveness and safety of different SGLT2 inhibitors vary based on their unique characteristics, which influence their selectivity, efficacy, and how they are processed in the body, making it important to understand these differences for optimal diabetes treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2 inhibitors: molecular design and potential differences in effect. Isaji, M.[2022]

In a study of 247 men with diabetes and prostate cancer, higher HbA1c levels were linked to more aggressive prostate tumors, as indicated by higher Gleason scores, suggesting that poor glycemic control may influence tumor biology.

Despite the association with tumor aggressiveness, higher HbA1c levels did not correlate with an increased risk of biochemical recurrence after treatment, indicating that glycemic control may not affect long-term outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycemic control and prostate cancer progression: results from the SEARCH database. Kim, HS., Presti, JC., Aronson, WJ., et al.[2022]

In a study involving 106 men with recurrent prostate carcinoma, rosiglitazone did not significantly improve prostate specific antigen doubling time (PSADT) compared to placebo, indicating it may not be effective for this condition.

Both treatment groups had similar rates of disease progression, suggesting that rosiglitazone does not provide a therapeutic advantage over placebo in managing rising PSA levels after prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum prostate-specific antigen level after radical prostatectomy and/or radiation therapy. Smith, MR., Manola, J., Kaufman, DS., et al.[2022]

SGLT2 inhibitors effectively lower HbA1c levels by 0.5-1.5% in patients with type 2 diabetes without causing hypoglycemia, making them a safe option for improving glycemic control.

These medications have a unique mechanism of action that allows them to be used alongside other diabetes treatments, but they require careful monitoring for potential safety issues, especially in elderly or high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2 inhibition in diabetes mellitus: rationale and clinical prospects. Ferrannini, E., Solini, A.[2022]

SGLT-2 inhibitors, like dapagliflozin, are a new class of oral diabetes medications that improve blood sugar control through an insulin-independent mechanism and also provide heart and kidney protection.

Recent research into SGLT-1 inhibition offers a promising new approach to managing high blood sugar, leading to the development of new drugs that target both SGLT-1 and SGLT-2, potentially enhancing treatment options for diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium-Glucose Cotransporter Inhibitors as Antidiabetic Drugs: Current Development and Future Perspectives. Maccari, R., Ottanà, R.[2023]

In a 12-week randomized controlled trial involving patients with type 2 diabetes, both empagliflozin and dapagliflozin significantly reduced body weight, fasting blood glucose, and HbA1c levels, indicating their efficacy as add-on therapies to traditional medications.

Empagliflozin was found to be more effective than dapagliflozin in reducing body mass index (BMI), fasting blood glucose, and HbA1c levels, while both medications had good safety profiles, with fewer urinary and genital infections reported in the empagliflozin group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Efficacy and Safety Profile of Sodium-Glucose Cotransporter-2 Inhibitors as Add-On Therapy in Patients With Type 2 Diabetes. Hussain, M., Elahi, A., Iqbal, J., et al.[2021]

Dapagliflozin is an effective treatment for type 2 diabetes, proven through multiple controlled clinical trials that assess its efficacy, safety, and tolerability.

It is approved by the FDA for use as a standalone therapy or in combination with other glucose-lowering medications, including insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. Davis, PN., Ndefo, UA., Oliver, A.[2021]

Dapagliflozin is an effective SGLT2 inhibitor for managing type 2 diabetes, showing consistent reductions in blood glucose levels and body weight over long-term follow-up periods of 1-4 years across various clinical trials.

It has a low risk of causing hypoglycemia and is generally well tolerated, although it can lead to genital infections, particularly in women, and is not recommended for patients with moderate to severe renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: a review of its use in patients with type 2 diabetes. Plosker, GL.[2022]

Sodium-glucose co-transporter-2 inhibitors (SGLT2-Is) are linked to a higher incidence of adverse events, particularly infections, metabolic disorders, renal issues, and reproductive system disorders, based on an analysis of 19,775 reports from international pharmacovigilance databases.

A significant concern is the potential for skin toxicity, including severe skin reactions, especially in women aged 18-65 using SGLT2-Is as their only diabetes treatment, highlighting the need for ongoing monitoring and vigilance by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events with sodium-glucose co-transporter-2 inhibitors: A global analysis of international spontaneous reporting systems. Raschi, E., Parisotto, M., Forcesi, E., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12330067/

Comparative risk of cancer associated with SGLT inhibitors ... Subgroup analyses revealed significantly lower risks for liver (RR = 0.76), lung (RR = 0.87), and prostate (RR = 0.75) cancers with SGLT2i.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666379124004099

The effect of SGLT2 inhibition on prostate cancer In the validation using electronic healthcare data, we showed that SGLT2 inhibitor use reduced the risk of prostate cancer by 23% in men with ...

3. withpower.com withpower.com/trial/phase-1-prostatic-neoplasms-8-2022-18a5a

SGLT2 Inhibition for High-Risk Prostate Cancer There is no direct evidence from the provided research that supports the effectiveness of Dapagliflozin specifically for high-risk prostate cancer.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04887935

Neoadjuvant SGLT2 Inhibition in Localized Prostate Cancer This is a pilot study of the tolerability and safety of neoadjuvant dapagliflozin for patients with unfavorable intermediate, high-risk, or very high-risk ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11333260/

Pharmacological targets of SGLT2 inhibition on prostate ... Our study suggested that SGLT2 inhibition could lower prostate cancer risk through uridine mediation. More mechanistic and clinical research is necessary.

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-09046

Dapagliflozin Propanediol for the Treatment of High-Risk ... This trial aims to see whether dapagliflozin propanediol may help treat prostate cancer because it can change glucose metabolism in the body and decrease the ...