Statins for Prostate Cancer

Recruiting at 1 trial location

Overseen By Jasmin M Brooks

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Medical University of South Carolina

Must not be taking: Statins, Fibrates, Niacin, others

Disqualifiers: Diabetes, Metastases, Liver disease, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether simvastatin, a medication typically used to lower cholesterol, can alter the behavior of certain immune cells in the prostate to enhance cancer-fighting abilities. Researchers are focusing on men recently diagnosed with localized prostate cancer who plan to undergo surgery. Participants will either take simvastatin for eight weeks before surgery or follow the usual care routine. Men diagnosed with this type of prostate cancer and planning surgery might be suitable for the trial. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

You may need to stop certain medications. If you are currently using statins, non-statin lipid-lowering drugs, or medications that are contraindicated with simvastatin, you cannot participate. These include drugs like gemfibrozil, cyclosporine, and certain antibiotics and antifungals. If you are on medications that require a lower dose of simvastatin, like verapamil or diltiazem, you may also be excluded. The protocol does not specify a washout period.

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

Research has shown that simvastatin, a common cholesterol-lowering drug, is usually well-tolerated. The FDA has already approved it for treating high cholesterol. Studies have found that men taking statins might have a lower risk of severe and deadly prostate cancer. Additionally, evidence indicates that statins can significantly reduce deaths specifically from prostate cancer.

While simvastatin is primarily used for cholesterol, its role in prostate cancer remains under investigation. Regarding safety, simvastatin is generally well-tolerated for other uses. Side effects may occur, but they are typically mild and manageable, suggesting a good safety profile for those considering trial participation. It is important to consult a healthcare provider about potential risks before joining a trial. ^{1 2 3 4 5}

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

Simvastatin is unique because, unlike standard prostate cancer treatments like surgery, radiation, or hormone therapy, it is typically used to lower cholesterol. Researchers are excited about its potential to inhibit cancer cell growth by targeting cholesterol pathways, which is a novel approach for prostate cancer. This repurposing of a common medication could offer a more accessible and less invasive option for patients, potentially with fewer side effects than traditional treatments.

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

Research has shown that simvastatin, a type of medication called a statin, might help treat prostate cancer. In this trial, participants in the experimental arm will receive simvastatin. Studies have found that taking statins can significantly lower the risk of dying from prostate cancer. Specifically, one study found that statins could cut the risk of developing prostate cancer by half. Additionally, statins may reduce the chance of cancer recurrence after surgery or radiation. These findings suggest that simvastatin could improve outcomes for prostate cancer patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Michael Marrone, PhD

Principal Investigator

Public Health Sciences

Are You a Good Fit for This Trial?

This trial is for men with intermediate to high-risk localized prostate cancer who are planning a prostatectomy. They must not have used statins in the past year, have no history of severe reactions to statins, no metastases or diabetes, normal liver function and cholesterol levels above 50mg/dL, and not be on certain other medications.

Inclusion Criteria

I am a man with prostate cancer at intermediate or high risk of recurrence.

Ability to provide written informed consent and willing to complete study procedures

I have chosen to have surgery to remove my prostate.

Exclusion Criteria

I am currently taking medication to lower my cholesterol.

My LDL cholesterol is below 50mg/dL.

I am currently taking medications that interact with simvastatin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 40 mg oral simvastatin daily for eight weeks prior to prostatectomy

8 weeks

2 visits (in-person) for clinical laboratory assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Simvastatin

Trial Overview The study tests if simvastatin can alter immune responses within the prostate by affecting T-reg cells in men undergoing surgery for prostate cancer. Participants will either receive simvastatin for 8 weeks before their operation or follow standard care without statins.

How Is the Trial Designed?

Group I: Simvastatin Experimental Treatment 1 Intervention

Patients randomized to the statin group will receive 40 mg oral simvastatin QD for eight weeks prior to prostatectomy, including the day of surgery.

Group II: Control Active Control 1 Intervention

Patients randomized to the control group receive no intervention prior to prostatectomy.

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

Simvastatin induces apoptosis in prostate cancer cells by inhibiting the intrinsic survival pathway, which involves enhancing the phosphorylation of Bad and reducing levels of pro-survival proteins like Bcl-2 and Bcl-xL.

The study also shows that simvastatin activates the extrinsic apoptosis pathway by increasing the expression of molecules such as TNF and Fas-L, suggesting that statins could be promising anti-cancer agents by targeting multiple apoptotic pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous modulation of the intrinsic and extrinsic pathways by simvastatin in mediating prostate cancer cell apoptosis. Goc, A., Kochuparambil, ST., Al-Husein, B., et al.[2022]

Simvastatin effectively reduces the viability of castrate-resistant prostate cancer cells (PC3 and DU-145) and increases apoptosis in a dose- and time-dependent manner, indicating its potential as a therapeutic agent.

The mechanism of action involves the inhibition of the nuclear factor-κB (NF-κB) pathway, specifically by preventing IκBα phosphorylation and nuclear translocation of the p50/p65 dimer, which leads to decreased expression of anti-apoptotic proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simvastatin induces apoptosis in castrate resistant prostate cancer cells by deregulating nuclear factor-κB pathway. Park, YH., Seo, SY., Lee, E., et al.[2016]

Statin use in advanced prostate cancer patients undergoing androgen deprivation therapy (ADT) was associated with a significant reduction in all-cause mortality (HR = 0.73) and cancer-specific mortality (HR = 0.64), based on a systematic review of nine studies involving over 100,000 patients.

While statins showed promising benefits for patients treated with ADT, the evidence for their efficacy in those with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone or enzalutamide was inconclusive, highlighting the need for further randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of statins on advanced prostate cancer patients with androgen deprivation therapy or abiraterone/enzalutamide: A systematic review and meta-analysis. Yang, H., Pang, L., Hu, X., et al.[2021]

In a study comparing high-dose and therapeutic-dose simvastatin on prostate cells, simvastatin was found to inhibit the growth of normal prostate cells more effectively than cancer cells, suggesting a potential selective effect.

The research indicates that the growth-inhibiting effects of simvastatin may not occur at standard clinical doses, as LDL-cholesterol can reverse these effects, implying that any benefits of statins in prostate cancer might be linked to their cholesterol-lowering properties rather than direct anti-cancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effects of high and low-dose simvastatin on prostate epithelial cells: the role of LDL. Murtola, TJ., Syvälä, H., Pennanen, P., et al.[2017]

Novel simvastatin-related compounds, particularly SVA, effectively suppress tumor growth in various prostate cancer cell lines by inhibiting cell proliferation, migration, and inducing apoptosis, showing promise as a treatment for castration-resistant prostate cancer.

These compounds not only block androgen receptor signaling but also inhibit the AKT pathway, suggesting a multifaceted mechanism of action that enhances their therapeutic potential, especially when combined with docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin derivatives as therapeutic agents for castration-resistant prostate cancer. Ingersoll, MA., Miller, DR., Martinez, O., et al.[2018]

The combination of the AR antagonist darolutamide and the statin simvastatin significantly suppressed the growth of castration-resistant prostate cancer (CRPC) cells, particularly in androgen-independent LNCaP-LA and 22Rv1 cell lines, indicating a potential new treatment strategy.

Simvastatin not only reduced the expression of androgen-stimulated genes but also altered the expression of key cell cycle regulators, suggesting that this combination therapy may target CRPC growth through both androgen-dependent and independent pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with novel androgen receptor antagonists and statin for castration-resistant prostate cancer. Nakayama, H., Sekine, Y., Oka, D., et al.[2022]

Simvastatin, a common cholesterol-lowering drug, has shown promising therapeutic effects against prostate cancer by inhibiting the Akt pathway, which is crucial for cell growth and survival, in both androgen-dependent and androgen-independent prostate cancer cells.

In a study using a PC3 xenograft model in mice, simvastatin treatment led to reduced tumor growth and lower prostate-specific antigen (PSA) levels, indicating its potential as a treatment option for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticancer efficacy of simvastatin on prostate cancer cells and tumor xenografts is associated with inhibition of Akt and reduced prostate-specific antigen expression. Kochuparambil, ST., Al-Husein, B., Goc, A., et al.[2013]

In a study involving 90 male nude mice with prostate cancer, the combination of simvastatin and ezetimibe actually accelerated tumor growth, suggesting that these cholesterol-lowering drugs may not be effective in slowing prostate cancer progression.

Ezetimibe reduced serum cholesterol levels by 15%, but paradoxically led to higher cholesterol levels in tumors, indicating that prostate tumors may adapt by increasing low-density lipoprotein receptors, which could be a mechanism of resistance against cholesterol-lowering therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence for Feedback Regulation Following Cholesterol Lowering Therapy in a Prostate Cancer Xenograft Model. Masko, EM., Alfaqih, MA., Solomon, KR., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8875347/

The Effects of Statins on Prostate Cancer Patients ... The combined results showed that statin use significantly reduced the risk of PCa-specific mortality (HR = 0.74, 95% CI = 0.59–0.91, p = 0.005, I2 = 0%, ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022356524462277

Anticancer Efficacy of Simvastatin on Prostate Cancer Cells ... An initial case-controlled study showed that the use of statins is associated with a 50% reduction in the risk of prostate cancer (Shannon et al., 2005), a ...

3. nature.com nature.com/articles/s41391-022-00554-1

Statins and prostate cancer—hype or hope? The ... Data from prospective observational studies generally reported a lower risk of fatal prostate cancer among statin users. There is some evidence ...

4. ar.iiarjournals.org ar.iiarjournals.org/content/43/12/5377

Simvastatin Induces Autophagy and Inhibits Proliferation in ... Furthermore, statin use has been reported to reduce the risk of recurrence after radical prostatectomy (24) and after radiation therapy (25, 26), as well as ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10281183/

Association Between Statin Exposure and Incidence and ... This study demonstrates that statins can reduce the incidence of PCA and improve prognosis, and are affected by population region and statin properties.

6. urotoday.com urotoday.com/conference-highlights/esmo-2018/esmo-2018-prostate-cancer/107814-esmo-2018-statin-use-and-outcome-in-metastatic-castration-resistant-prostate-cancer-patients-treated-in-the-tropic-trial.html

Statin Use and Outcome in Metastatic Castration-Resistant ... These studies suggest that long-term statin use may be associated with a reduced risk of prostate cancer. This study utilized data from the phase III TROPIC ...