Vytorin for Prostate Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Cedars-Sinai Medical Center
Must be taking: Statins, Ezetimibe
Must not be taking: CYP3A4 inhibitors, Gemfibrozil
Disqualifiers: Liver failure, Severe myalgia, others
No Placebo Group
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?To test the hypothesis that intensive cholesterol lowering (iCL) therapy has anti-tumor immune modulating activity, the investigators will conduct an open-label, single-arm phase II trial in prostate cancer patients who are in active surveillance and undergoing a planned surveillance biopsy in 3-6 months. Eligible patients will initiate iCL with Vytorin®(group 1, 2, and 3), an FDA-approved combination of ezetimibe and simvastatin used to lower atherogenic low density lipoprotein cholesterol (LDL-C) or Ezetimibe (group 4). Starting dose will be determined by current statin use and LDL-C levels. Dose modifications of VYTORIN will be employed with the goal of achieving LDL-C \<70 mg/dl. Dose adjustment is not allowed for ezetimibe.
Will I have to stop taking my current medications?
The trial does not specify if you must stop taking your current medications, but you cannot participate if you are using certain medications that interact with statins or ezetimibe. It's best to discuss your current medications with the trial team to see if any adjustments are needed.
What data supports the effectiveness of the drug Vytorin for prostate cancer?
Research suggests that statins, like simvastatin (a component of Vytorin), may improve survival in advanced prostate cancer, especially when used with other treatments like androgen deprivation therapy. Additionally, simvastatin has shown potential in enhancing the effects of other cancer treatments in prostate cancer models.
12345Is Vytorin (Ezetimibe/Simvastatin) safe for use in humans?
Vytorin, which combines ezetimibe and simvastatin, is generally considered safe for humans as it is FDA-approved for lowering cholesterol. Studies have shown it may also help slow prostate cancer growth by reducing cholesterol levels, but its safety profile is primarily based on its use for cholesterol management.
13467How does the drug Vytorin differ from other treatments for prostate cancer?
Vytorin, a combination of ezetimibe and simvastatin, is unique because it targets cholesterol levels, which may help slow prostate cancer growth by reducing tumor blood vessel formation (angiogenesis) and modifying lipid profiles associated with poor outcomes. This approach is different from standard prostate cancer treatments that typically focus on hormone levels or chemotherapy.
14568Eligibility Criteria
This trial is for men over 50 with prostate cancer who are being closely monitored (active surveillance) and have a planned biopsy in the next 3-6 months. Participants should be willing to follow study procedures, may have conditions like hypertension, high cholesterol, diabetes, or a family history of heart disease, and could be current/former smokers with BMI >25.Inclusion Criteria
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
I can take pills and will follow a daily medication routine.
+5 more
Exclusion Criteria
History of allergic or severe reaction to either study agent
I have severe liver problems.
I am currently taking the highest dose of VYTORIN.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive intensive cholesterol-lowering therapy with Vytorin or Ezetimibe
3-6 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing Vytorin®, a combination of ezetimibe and simvastatin that lowers 'bad' LDL cholesterol. It's believed this intensive cholesterol-lowering might help the immune system fight cancer. Patients will start on doses based on their current statin use and LDL levels, aiming to get LDL under 70 mg/dl.
1Treatment groups
Experimental Treatment
Group I: Intensive Lipid LoweringExperimental Treatment2 Interventions
Single arm with dual agents (ezetimibe and simvastatin) or single agent (ezetimibe). These agents target the two primary sources of cholesterol, absorption in the gut (ezetimibe) and synthesis in the liver (simvastatin). The dual agents are available in a single pill that is FDA approved and sold under the trade name, Vytorin.
Intensive Cholesterol-Lowering Therapy is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Vytorin for:
- Hyperlipidemia
- Homozygous familial hypercholesterolemia
🇪🇺 Approved in European Union as Inegy for:
- Hyperlipidemia
- Homozygous familial hypercholesterolemia
🇨🇦 Approved in Canada as Vytorin for:
- Hyperlipidemia
- Homozygous familial hypercholesterolemia
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cedars-Sinai Medical CenterLos Angeles, CA
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Who Is Running the Clinical Trial?
Cedars-Sinai Medical CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Evidence for Feedback Regulation Following Cholesterol Lowering Therapy in a Prostate Cancer Xenograft Model. [2020]Epidemiologic data suggest cholesterol-lowering drugs may prevent the progression of prostate cancer, but not the incidence of the disease. However, the association of combination therapy in cholesterol reduction on prostate or any cancer is unclear. In this study, we compared the effects of the cholesterol lowering drugs simvastatin and ezetimibe alone or in combination on the growth of LAPC-4 prostate cancer in vivo xenografts.
Statin Use and Survival Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer: A Systematic Review and Meta-analysis. [2022]Epidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies.
The effect of statins on advanced prostate cancer patients with androgen deprivation therapy or abiraterone/enzalutamide: A systematic review and meta-analysis. [2021]To evaluate the effects of statin use on the treatment outcomes (i.e. overall survival and cancer-specific survival) among advanced prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) or abiraterone/enzalutamide.
Synergistic antitumor interaction of valproic acid and simvastatin sensitizes prostate cancer to docetaxel by targeting CSCs compartment via YAP inhibition. [2021]Despite the introduction of several novel therapeutic approaches that improved survival, metastatic castration-resistant prostate cancer (mCRPC) remains an incurable disease. Herein we report the synergistic antitumor interaction between two well-known drugs used for years in clinical practice, the antiepileptic agent with histone deacetylase inhibitory activity valproic acid and the cholesterol lowering agent simvastatin, in mCRPC models.
The impact of statins in combination with androgen deprivation therapyin patients with advanced prostate cancer: A large observational study. [2020]Statins are thought to possess antineoplastic properties related to their effect on cell proliferation and steroidogenesis. Progression to castrate resistant prostate cancer (CaP) includes de-regulation of androgen synthesis suggesting a role for statins in this setting. Our goal was to assess the role of statin use on oncologic outcomes in patients with advanced CaP being treated with androgen deprivation therapy (ADT).
Ezetimibe is an inhibitor of tumor angiogenesis. [2021]Epidemiological and preclinical observations have suggested a role for one or more products of the mevalonate/cholesterol biosynthesis pathway in the progression of prostate cancer. In this study, we used ezetimibe (Zetia), a specific, FDA-approved, cholesterol uptake-blocking drug, in combination with either a hyper- or hypocholesterolemic diet, to show that elevated circulating cholesterol levels promote, whereas a reduction in circulating cholesterol levels retard, the growth of human prostate cancer xenograft tumors in mice. Circulating cholesterol levels also modified tumor angiogenesis; higher cholesterol levels increased microvessel density and other indicators of vascularity. Consistent with these data, the reduction of cholesterol levels also increased the levels of the angiogenesis inhibitor thrombospondin-1 in the xenografts. Our results thus suggest that hypercholesterolemia directly accelerates the growth of prostate carcinomas, and that the pharmacological reduction of serum cholesterol levels may retard prostate cancer growth by inhibiting tumor angiogenesis.
Longer-term Lipid-lowering Drug Use and Risk of Incident and Fatal Prostate Cancer in Black and White Men in the ARIC Study. [2022]Lipid-lowering medications, particularly statins, may protect against aggressive prostate cancer. Fatal prostate cancer, the most clinically relevant outcome, remains understudied for this association. We prospectively studied lipid-lowering medication use and both incident and fatal prostate cancer in black and white men in the Atherosclerosis Risk in Communities (ARIC) study. A total of 6,518 men without cancer at visit 2 (1990-1992), the start of the statin era, were followed for prostate cancer incidence and death through 2012. Medication use was collected during study visits and telephone calls at up to nine time points during follow-up. Cox regression was used to estimate HR and 95% confidence intervals (CI) of total (white N = 541, black N = 259) and fatal (white N = 56, black N = 34) prostate cancer overall and by race. Lipid-lowering medication use was modeled as time-dependent current use or duration (never, <10, and ≥10 years). By visit 4 (1996-1998), 21% of white and 11% of black men had used a lipid-lowering medication, mostly statins. There was a suggestion that current users were less likely to die from prostate cancer than nonusers (HR = 0.67, 95% CI = 0.42-1.07) after multivariable adjustment. We observed no statistically significant differences between black and white men. Current use was not associated with incident prostate cancer, although long-term use was statistically significantly inversely associated with incidence (HR = 0.68; 95% CI = 0.50-0.92). Long-term lipid-lowering medication use was associated with lower risk of prostate cancer. Current use was possibly associated with fatal prostate cancer.
Modulation of Plasma Lipidomic Profiles in Metastatic Castration-Resistant Prostate Cancer by Simvastatin. [2023]Elevated circulating sphingolipids are associated with shorter overall survival and therapeutic resistance in metastatic castration-resistant prostate cancer (mCRPC), suggesting that perturbations in sphingolipid metabolism promotes prostate cancer growth. This study assessed whether addition of simvastatin to standard treatment for mCRPC can modify a poor prognostic circulating lipidomic profile represented by a validated 3-lipid signature (3LS). Men with mCRPC (n = 27) who were not on a lipid-lowering agent, were given simvastatin for 12 weeks (40 mg orally, once daily) with commencement of standard treatment. Lipidomic profiling was performed on their plasma sampled at baseline and after 12 weeks of treatment. Only 11 men had the poor prognostic 3LS at baseline, of whom five (45%) did not retain the 3LS after simvastatin treatment (expected conversion rate with standard treatment = 19%). At baseline, the plasma profiles of men with the 3LS displayed higher levels (p