Fenofibrate for Cervical Cancer

Overseen By Lindsay A Ferguson, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Lindsay Ferguson, MD

Disqualifiers: Hepatic insufficiency, Renal insufficiency, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2-4 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Fenofibrate, a drug typically used to lower cholesterol, to determine if it can treat cervical cancer caused by HPV. Researchers believe Fenofibrate might restore normal function to a protein called p53, which helps stop tumor growth. The trial will examine the drug's effects on HPV-positive cervical cancers and cervical dysplasia, a precancerous condition. It is suitable for those with confirmed high-grade dysplasia or cervical cancer who qualify for surgery or chemoradiation. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to contribute to groundbreaking research.

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.

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

Research has shown that fenofibrate is generally safe. This cholesterol-lowering drug has already received approval for other uses, indicating it has passed safety checks for those conditions.

While researchers continue to study fenofibrate for treating HPV-positive cervical cancers and related conditions, its prior use for other health issues suggests it is usually well-tolerated. No specific reports of major safety concerns have emerged when used for this type of cancer treatment. However, since this is early research for its use in cancer, the primary goal is to learn more about its safety and effectiveness for this new purpose. ^{1 2 3 4 5}

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

Unlike the standard treatments for cervical cancer, which typically include surgery, radiation, and chemotherapy, the drug Fenofibrate introduces a novel approach by potentially interfering with the cancer's lipid metabolism. Researchers are excited about Fenofibrate because it targets a different biological pathway, offering a fresh strategy against cervical cancer. This could make it an effective adjunct to traditional treatments, possibly enhancing their effectiveness or reducing side effects. Additionally, Fenofibrate's role as a lipid-lowering agent already used in treating high cholesterol suggests it might have a well-understood safety profile, which is promising for its use in cancer therapy.

What evidence suggests that Fenofibrate might be an effective treatment for cervical cancer?

Research has shown that Fenofibrate, a drug typically used to lower cholesterol, might help treat cervical cancers linked to HPV. Early studies suggest it can restore the normal function of p53, a protein that usually prevents tumors from forming. This indicates that Fenofibrate could potentially stop these tumors from growing. It may also alter how these cancer cells use energy, making them less likely to grow and spread. In this trial, participants with high-grade dysplasia will receive Fenofibrate alongside an excisional procedure, while those with invasive cervical cancer will receive it in combination with either a hysterectomy or chemoradiation. These findings suggest that Fenofibrate could be promising in managing cervical cancer and cervical dysplasia related to HPV. ^{1 2 3 4 5}

Who Is on the Research Team?

Lindsay Ferguson, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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.

You are currently being treated at University Hospital Seidman Cancer Center.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Fenofibrate

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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

Lindsay Ferguson, MD

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

Fenofibrate was found to reduce the viability of HeLa cervical cancer cells in a dose-dependent manner, primarily through inducing cell cycle arrest in the G0-G1 phase and triggering caspase-dependent apoptosis.

The study also revealed that fenofibrate activated autophagy, which may help cancer cells survive; thus, combining fenofibrate with an autophagy inhibitor could enhance its anticancer effects against cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenofibrate Exerts Anticancer Effects on Human Cervical Cancer HeLa Cells via Caspase-Dependent Apoptosis and Cell Cycle Arrest. Song, SY., Lee, SY., Ko, YB., et al.[2022]

Fenofibrate effectively lowers blood lipids in both aging rats and humans with various types of hyperlipoproteinaemia, showing sustained activity over long-term treatment (up to 20 months).

In comparative studies, fenofibrate (400 mg/day) outperformed clofibrate and showed slightly better results than gemfibrozil and bezafibrate, while also normalizing platelet aggregation in patients with type IIb hyperlipoproteinaemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacology of fenofibrate (author's transl)]. Kritchevsky, D.[2013]

Fenofibrate is a well-tolerated lipid-lowering medication with a low incidence of adverse effects (6%) based on extensive clinical trials involving over 7,145 patients and 10 years of post-marketing experience in Europe.

While some mild liver and renal effects were noted in preclinical studies, significant safety concerns such as cancer have not been associated with fenofibrate in over a decade of clinical use, indicating its overall safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of fenofibrate--US and worldwide experience. Roberts, WC.[2018]

Fenofibrate effectively induces apoptosis in mantle cell lymphoma (MCL) cells, reducing viable cell numbers by 50% at a concentration of approximately 20 microM over 72 hours, demonstrating its potential as a treatment option.

The mechanism of action involves the inhibition of the TNF-alpha/NF-kappaB signaling pathway, and since fenofibrate is already considered safe for human use, it could be a promising therapeutic strategy for patients with MCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenofibrate induces effective apoptosis in mantle cell lymphoma by inhibiting the TNFalpha/NF-kappaB signaling axis. Zak, Z., Gelebart, P., Lai, R.[2013]

Fenofibrate significantly inhibits the growth of human ovarian cancer cells (SKOV3) in vitro, with a maximum inhibition rate of 72.41% after 72 hours of treatment at higher concentrations.

The drug also induces apoptosis in SKOV3 cells in a concentration-dependent manner and reduces cell migration, suggesting potential therapeutic effects against ovarian cancer, although the exact mechanisms require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of fenofibrate on the growth and migration of ovarian cancer cells in vitro]. Wang, H., He, CH., Bai, LP., et al.[2018]

In a study of 31 type 2 diabetic patients, fenofibrate treatment significantly improved glycemic control by lowering fasting and postprandial blood glucose levels, as well as reducing fasting serum insulin and leptin levels over 3 months.

Fenofibrate also effectively reduced triglyceride levels and increased HDL cholesterol, demonstrating its benefits for both lipid profiles and insulin resistance, while being well tolerated by all participants.

NCBI (Pubmed)

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. Damci, T., Tatliagac, S., Osar, Z., et al.[2022]

Fenofibrate effectively induces apoptosis in triple-negative breast cancer (TNBC) cells through a mechanism that does not depend on PPAR-α, with a maximum apoptosis rate of 41.8% observed in vitro, and it also slows tumor growth in vivo using a mouse model.

The drug activates the NF-κB pathway, which plays a crucial role in its anti-tumor effects, and it demonstrates a good safety profile, indicating its potential as a novel therapeutic option for TNBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenofibrate induces apoptosis of triple-negative breast cancer cells via activation of NF-κB pathway. Li, T., Zhang, Q., Zhang, J., et al.[2022]

In a study involving 64 women using various progestin-dominant oral contraceptives, fenofibrate was used as an adjuvant therapy to improve lipid metabolism and mitigate adverse metabolic effects.

The results suggest that Lipanthyl (fenofibrate) therapy is effective in maintaining safe contraception while promoting better lipid profiles, highlighting its potential as a protective treatment in women on hormonal contraceptives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective role of lipanthyl in women taking oral contraceptives. Sásdi, A.[2013]

Fenofibrate, a drug primarily used to lower cholesterol and triglycerides, shows promising anticancer effects in various human cancer cell lines, including breast, liver, and lung cancers, suggesting its potential as a repurposed cancer treatment.

Studies indicate that fenofibrate may work through multiple mechanisms, such as inducing apoptosis and inhibiting cell migration, and its efficacy has been supported by results from xenograft mouse models, highlighting its safety and effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticancer Properties of Fenofibrate: A Repurposing Use. Lian, X., Wang, G., Zhou, H., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06191133

Study Details | NCT06191133 | Fenofibrate in Patients With ... The purpose of this study is to understand how Fenofibrate can be used to treat HPV-positive cervical cancers and cervical dysplasia.

2. trialx.com trialx.com/clinical-trials/listings/319913/fenofibrate-in-patients-with-cervical-intraepithelial-neoplasia-and-invasive-cervical-carcinoma/

Fenofibrate in Patients With Cervical Intraepithelial ... The purpose of this study is to understand how Fenofibrate can be used to treat HPV-positive cervical cancers and cervical dysplasia.

3. withpower.com withpower.com/trial/phase-1-cervical-intraepithelial-neoplasia-1-2024-5278e

Fenofibrate for Cervical Cancer 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 ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-08685

Fenofibrate for the Treatment of Patients with Cervical ... This phase I trial tests the safety, side effects, and how well fenofibrate works in treating patients with cervical dysplasia or invasive cervical cancer

5. news.uhhospitals.org news.uhhospitals.org/news-releases/articles/2025/02/cancer-cholesterol-drug-clinical-trial

Cancer cholesterol drug clinical trial | News - UH Newsroom Published pre-clinical results show fenofibrate restores function of key tumor suppressor gene in these cancers. The group's pre-clinical ...