Fenofibrate for Cervical Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Lindsay Ferguson, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Lindsay Ferguson, MD

Disqualifiers: Hepatic insufficiency, Renal insufficiency, Pregnancy, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

Normally, p53 helps prevent tumors from forming in the body. Early studies have shown that Fenofibrate, a cholesterol-lowering drug, can restore normal function to p53 and can change the metabolism of HPV-positive tumors in a way that stops the growth of tumors. The purpose of this study is to understand how Fenofibrate can be used to treat HPV-positive cervical cancers and cervical dysplasia. Researchers will examine collected tissue samples and investigate various genes and proteins to see whether Fenofibrate has an effect on HPV-positive cervical cancers and cervical dysplasia.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug fenofibrate for cervical cancer?

Research shows that fenofibrate can cause cancer cells, including cervical cancer cells, to die and stop growing by triggering a process called apoptosis (a type of programmed cell death) and halting the cell cycle. This suggests it might be effective against cervical cancer. ^{1 2 3 4 5}

Is fenofibrate safe for use in humans?

Fenofibrate has been used for many years to lower cholesterol and triglycerides, and it is generally considered safe with a low frequency of side effects. Common side effects include stomach issues, muscle pain, skin problems, and dizziness. Long-term studies and extensive use in Europe and the US have shown it to be well-tolerated, with serious side effects being rare. ^{1 2 4 5 6}

How does the drug fenofibrate work differently for cervical cancer compared to other treatments?

Fenofibrate is unique in treating cervical cancer because it works by inducing apoptosis (programmed cell death) and causing cell cycle arrest in cancer cells, which is different from traditional chemotherapy that often targets rapidly dividing cells more broadly. ^{1 4 7 8 9}

Research Team

Lindsay Ferguson, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Eligibility Criteria

This trial is for English-speaking adults over 18 with high-grade cervical dysplasia or cervical cancer (squamous cell, adenocarcinoma, adenosquamous carcinoma) who are being treated at University Hospital Seidman Cancer Center. They must be eligible for surgical management or chemoradiation and able to give informed consent.

Inclusion Criteria

I am eligible for surgery or chemoradiation as treatment.

I can understand and am willing to sign the consent form.

I am 18 years old or older.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 200mg of Fenofibrate daily for 2-4 weeks until their excisional procedure or definitive hysterectomy/chemoradiation

2-4 weeks

Follow-up

Participants are monitored for changes in p53 levels and tumor metabolic status up to six weeks after study enrollment

6 weeks

Treatment Details

Interventions

• Fenofibrate (Other)

Trial Overview Researchers are testing if Fenofibrate can treat HPV-positive cervical cancers and dysplasia by restoring p53 function and altering tumor metabolism. The study involves tissue sample analysis to observe the drug's effects on genes and proteins related to these conditions.

Participant Groups

Group I: Hysterectomy or chemoradiation + fenofibrate Experimental Treatment 3 Interventions

Participants with invasive cervical cancer will receive 200mg of Fenofibrate starting on the day of enrollment and will continue the drug administration daily for 2-4 weeks +/- 7 days until their definitive hysterectomy or chemoradiation

Group II: Excisional procedure + Fenofibrate Experimental Treatment 2 Interventions

Participants with high-grade dysplasia will receive 200mg of Fenofibrate starting on the day of enrollment and will continue the drug administration daily for 2-4 weeks +/- 7 days until their excisional procedure

Fenofibrate is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Fenofibrate for:

• High cholesterol
• Severe high triglycerides

🇪🇺 Approved in European Union as Fenofibrate for:

• Mixed hyperlipidemia
• Primary hypercholesterolemia
• Severe hypertriglyceridemia

🇨🇦 Approved in Canada as Fenofibrate for:

• Hyperlipidemia
• Hypertriglyceridemia

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center Cleveland, OH

Who Is Running the Clinical Trial?

Lindsay Ferguson, MD

Lead Sponsor

Trials

1

Patients Recruited

20+

References

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

Fenofibrate Exerts Anticancer Effects on Human Cervical Cancer HeLa Cells via Caspase-Dependent Apoptosis and Cell Cycle Arrest. [2022] In the present study, we attempted to identify the effects of fenofibrate on human cervical cancer cells.

2. China pubmed.ncbi.nlm.nih.gov

[Effects of fenofibrate on the growth and migration of ovarian cancer cells in vitro]. [2018] To investigate the effects of fenofibrate, a lipid-lowering drug, on the growth and migration of human ovarian cancer cells SKOV3 in vitro.

3. England pubmed.ncbi.nlm.nih.gov

Fenofibrate induces effective apoptosis in mantle cell lymphoma by inhibiting the TNFalpha/NF-kappaB signaling axis. [2013] Mantle cell lymphoma (MCL) is a type of aggressive B-cell non-Hodgkin's lymphoma characterized by frequent resistance to conventional chemotherapy. In this study we provided evidence that fenofibrate, which is widely known as an agonist for peroxisome proliferator-activated receptor-alpha (PPARalpha), can induce effective apoptosis in treating MCL cells. Addition of fenofibrate to MCL cell lines significantly decreased the number of viable cells by 50% at approximately 20 microM at 72 h. This decrease in cell growth was due to apoptosis, as evidenced by the cleavage of caspase 3 and poly(ADP-ribose) polymerase. The fenofibrate-mediated effects were not significantly affected by GW6471, a specific PPARalpha antagonist. Using an apoptosis pathway-specific oligonucleotide array, we found that fenofibrate significantly downregulated several pro-survival genes, including tumor necrosis factor-alpha (TNFalpha). Importantly, addition of recombinant TNF-alpha conferred partial protection against fenofibrate-induced apoptosis. Fenofibrate also decreased the nuclear translocation of nuclear factor (NF)-kappaB-p65 and significantly inhibited the DNA binding of NF-kappaB in a dose-dependent manner. To conclude, fenofibrate shows efficacy against MCL, and the mechanism can be attributed to its inhibitory effects on the TNF-alpha/NF-kappaB signaling axis. In view of the documented safety of fenofibrate in humans, it may provide a valuable therapeutic option for MCL patients.

4. England pubmed.ncbi.nlm.nih.gov

Fenofibrate induces apoptosis of triple-negative breast cancer cells via activation of NF-κB pathway. [2022] There are a lot of unmet needs in patients with triple-negative breast cancer (TNBC). Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, has been used for decades to treat hypertriglyceridaemia and mixed dyslipidaemia. Recent studies show that it might have anti-tumor effects, however, the mechanism remains unclear. Here, we assessed the ability of fenofibrate to induce apoptosis of TNBC in vitro and in vivo and explored involved mechanisms.

5. Australia pubmed.ncbi.nlm.nih.gov

Anticancer Properties of Fenofibrate: A Repurposing Use. [2022] Cancer is a leading cause of death throughout the world, and cancer therapy remains a big medical challenge in terms of both its therapeutic efficacy and safety. Therefore, to find out a safe anticancer drug has been long goal for oncologist and medical scientists. Among clinically used medicines with no or little toxicity, fenofibrate is a drug of the fibrate class that plays an important role in lowering the levels of serum cholesterol and triglycerides while elevating the levels of high-density lipoproteins. Recently, several studies have implied that fenofibrate may exert anticancer effects via a variety of pathways involved in apoptosis, cell-cycle arrest, invasion, and migration. Given the great potential that fenofibrate may have anticancer effects, this review was to investigate all published works which directly or indirectly support the anticancer activity of fenofibrate. These studies provide evidence that fenofibrate exerted antitumor effects in several human cancer cell lines, such as breast, liver, glioma, prostate, pancreas, and lung cancer cell lines. Among these studies some have further confirmed the possibility and efficacy of fenofibrate anticancer in xenograft mouse models. In the last part of this review, we also discuss the potential mechanisms of action of fenofibrate based on the available information. Overall, we may repurpose fenofibrate as an anticancer drug in cancer treatment, which urgently need further and comprehensively investigated.

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of fenofibrate--US and worldwide experience. [2018] Fenofibrate is a fibric acid derivative with enhanced potency and specificity of action on lipids. Preclinical toxicology reveals minimal toxic effects; dose-related changes occurred seldom, with only hepatic effects in rodents (mainly enzyme changes), some renal effects in dogs, and no reactions in monkeys. Teratogenicity tests were negative, and mutagenicity was not associated with fenofibrate. Carcinogenicity was evident in rodents with liver carcinoma at doses of 12 or 40 times the human dose, but cancer has not been associated with fenofibrate in over 10 years of clinical research and use. European experience with fenofibrate involved 7,145 patients in short- and long-term clinical trials, plus 10 years of marketing experience with a patient exposure of 6 million patient-years. Adverse effects were relatively low in frequency (6%) in the European clinical trials and manifested as gastrointestinal effects, muscle pain, skin problems, and sweating or dizziness. Short- and long-term fenofibrate studies revealed basically the same scope and frequency of adverse effects. Experience in US clinical trials mirrored the European experience; three types of adverse effects occurred more commonly in fenofibrate patients versus placebo: skin reactions, neurologic effects, and musculoskeletal reactions. Laboratory tests were mildly abnormal for liver function, leukocytes, and hemoglobin; these reactions were significant enough to be considered adverse drug experiences only occasionally. Hepatobiliary tests for lithogenicity showed an increase in cholesterol saturation, but gallstones seldom have been associated with fenofibrate. Postmarketing, open experiences in Europe over 10 years have been consistent with the study results. The rate of reactions has been low (about 115/year or a 0.3% incidence rate). The reactions noted in these spontaneous reports were hepatic, renal, gallstones, cutaneous, hematologic, sexual asthenia, and weight loss. In general, fenofibrate can be considered a safe and well-tolerated lipid-lowering drug that has been scrutinized extensively for safety in clinical research and during an already long marketing period in Europe.

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

Fenofibrate treatment is associated with better glycemic control and lower serum leptin and insulin levels in type 2 diabetic patients with hypertriglyceridemia. [2022] Background: Hertriglyceridemia is commonly encountered in type 2 diabetic patients. Fibrates are a group of drugs that efficiently decrease triglycerides, increase HDL, and improve the prognosis in both diabetic and nondiabetic patients. However, the effects of fibrates on glycemic control, blood pressure, fasting serum insulin, and leptin concentrations are not clear. The present study addresses the question of whether fenofibrate treatment in hypertriglyceridemic type 2 diabetic patients leads to changes in metabolic control, body mass index, leptin, free fatty acids, plasma insulin, and blood pressure. Methods: Thirty-one type 2 diabetic patients who had serum triglyceride levels between 250 and 400 mg/dl were included in the study. They were given 250 mg/day fenofibrate once daily for 3 months. Antidiabetic and antihypertensive treatments were kept unchanged throughout the study. Results: Fenofibrate treatment resulted in better glycemic control, as evidenced by lower fasting and postprandial blood glucose and HbAlc, decreased fasting serum insulin and leptin levels, as well as a reduction in hypertrigyceridemia and serum free fatty acids, and an increase in HDL cholesterol. Blood pressure, body mass index, and LDL remained unchanged. Fenofibrate was well tolerated in all patients. Conclusion: Fenofibrate treatment in hypertriglyceridemic type 2 diabetic patients is beneficial not only in terms of lipid profile, but also for glycemic control and insulin resistance.

8. Hungary pubmed.ncbi.nlm.nih.gov

Protective role of lipanthyl in women taking oral contraceptives. [2013] Fenofibrate subdoses were applied as an adjuvant therapy in 64 women for improving lipid metabolism. The women took different oral contraceptives mainly with progestin dominance and the prevention of the unfavourable metabolic effects with drug therapy was indicated for maintaining safe contraception which was absolutely necessary for health and other reasons. Protective Lipanthyl therapy seemed to be very useful for this purpose.

9. France pubmed.ncbi.nlm.nih.gov

[Pharmacology of fenofibrate (author's transl)]. [2013] Fenofibrate is one of several compounds with substituted-2-phenoxy-isobutyric acids and esters. In ageing rats receiving a hyperlipidaemic diet or injections of triton, fenofibrate lowers blood lipids as much as, or more than other antilipaemic agents. It is active in man against the main types (IIa, IIb and IV) of hyperlipoproteinaemia (HLP), and this activity is sustained throughout treatment (20 months in one study). In comparative studies, the effects of fenofibrate (400 mg/day) on the lipoprotein fractions tested were superior to those of clofibrate (2 g/day) and slightly superior to those of gemfibrosil (800 mg/day) and bezafibrate (600 mg/day). The drug also enhanced the lipid-lowering effects of colestipol. In doses of 300 mg/day fenofibrate produced a significant 13-15% decrease in apoprotein B with a concomitant 19-28% increase in apoprotein A. Fenofibrate was also found to normalize platelet aggregation in patients with type IIb HLP. In animals fenofibrate is excreted in equal amounts in the urine and faeces; in man, urinary excretion predominates (85-90%). The serum half-life curve is diphasic, with a rapid (5 hours) slope and a slow (17 hours) slope. In a 10-day study conducted on 10 volunteers serum levels of fenofibric acid remained remarkably constant, indicating lack of accumulation. New data on the mode of action are needed to further differentiate fenofibrate from clofibrate.