5-Fluorouracil Injection for Chalazion

(CTS Trial)

Overseen By Simona Vuletic, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Washington

Disqualifiers: Chalazia less than one month

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new treatment with 5-fluorouracil, a cancer-fighting drug, can effectively treat chalazia (styes) compared to a steroid injection or minor surgery. Participants will receive one of four treatments: a mix of 5-fluorouracil and a steroid, just the steroid (triamcinolone acetonide), the standard minor surgery, or just 5-fluorouracil. The goal is to determine which treatment works best. Individuals with one or more styes in a single eyelid, present for over a month without previous injections or surgery, might be suitable for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications.

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

A previous study found that injecting 5-fluorouracil (5-FU) directly into scars around the eyes and face was safe. Pain at the injection site was the most common side effect. Another study showed that a single injection of 5-FU mixed with triamcinolone acetonide significantly reduced the size of chalazia (styes) without major safety concerns.

Research on using triamcinolone acetonide alone also shows it is generally safe for treating chalazia. One study reported a success rate of 50% to 95% in resolving chalazia, and the treatment was well-tolerated. However, it should not be used in patients with active eye infections.

Both treatments have been studied for chalazia and are considered well-tolerated, though some discomfort at the injection site is possible. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatment options for chalazion, which often include surgical removal or steroid injections, the 5-fluorouracil (5-FU) injection offers a unique approach by using an antimetabolite to target and reduce the lesion directly. Researchers are excited about 5-FU because it may reduce inflammation and size more effectively without the need for surgery. Additionally, the combination of 5-FU with triamcinolone in one of the study arms leverages the anti-inflammatory properties of steroids alongside 5-FU’s mechanism, potentially offering a quicker and less invasive treatment option.

What evidence suggests that 5-fluorouracil injection might be an effective treatment for chalazion?

Research has shown that a single injection of 5-fluorouracil (5-FU), which participants in this trial may receive, can shrink a chalazion, or stye, in about 64% of cases. This treatment is as effective as the steroid triamcinolone, another option in this trial, and the surgical method of cutting and cleaning out the stye. Studies also suggest that combining 5-FU with triamcinolone, a combination tested in this trial, can successfully treat chalazia in a similar number of cases. For triamcinolone alone, some studies report success rates as high as 78.6%. Overall, both 5-FU and triamcinolone are effective options for treating chalazia. ^{1 2 3 4 6}

Who Is on the Research Team?

Matthew M Zhang, MD

Principal Investigator

University of Washington Eye Institute

Are You a Good Fit for This Trial?

This trial is for individuals with one or more chalazia (styes) on a single eyelid. Participants must have had the chalazion for at least one month and should not have received any previous injections or surgical treatments for it.

Inclusion Criteria

I have one or more chalazia on one eyelid.

Exclusion Criteria

My chalazion has been present for less than a month and hasn't been treated by injection or surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of the four standard-of-care treatments for chalazia: incision and curettage, local injection of triamcinolone, local injection of 5-FU, or local injection of combination triamcinolone/5-FU

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 5-fluorouracil Injection
• Triamcinolone Acetonide

Trial Overview

The study is testing the effectiveness of a local injection of 5-fluorouracil compared to an injection of triamcinolone (a steroid), a mixture of both, or surgery (incision and curettage) in treating chalazia.

How Is the Trial Designed?

Group I: Injection of triamcinolone/5FU mixture Active Control 2 Interventions

0.1 ml of a 4:1 mixture of 4 parts 5-FU and 1 part triamcinolone is injected in the lesion.

Group II: Injection of Triamcinolone Acetonide Active Control 2 Interventions

0.1 ml of triamcinolone is injected directly in the chalazion.

Group III: Incision and Curettage Active Control 1 Intervention

A vertical incision over the area of chalazion will be done. Inflammatory material will be removed and the chalazion capsule will be excised.

Group IV: Injection of 5-fluorouracil Active Control 2 Interventions

0.1 ml of 5-fluorouracil is injected directly in the lesion transconjunctivally.

5-fluorouracil Injection is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Oesophageal cancer
• Cervical cancer
• Skin cancers

Approved in United States as Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Anal cancer
• Cervical cancer
• Head and neck cancers
• Skin cancers

Approved in Canada as Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Oesophageal cancer
• Cervical cancer
• Skin cancers

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Published Research Related to This Trial

The study developed a bioadhesive gel formulation of 5-Fluorouracil (5-FU) using Carbopol 934, which showed superior skin deposition and bioadhesive strength compared to traditional cream formulations, making it a more effective option for localized delivery in treating skin cancers and actinic keratosis.

The optimized bioadhesive gel demonstrated minimal skin irritation, with only slight erythema observed, while the marketed cream caused more significant irritation, indicating that the new formulation may be safer for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development, characterization and in vivo localization study of topical 5-fluorouracil gels: a comparative study with conventional formulation. Jain, SK., Puri, R.[2022]

In a study involving eight eyes from seven patients with severe dry eye disease due to Stevens-Johnson syndrome, a single subconjunctival injection of 5-fluorouracil (5-FU) led to visible improvements in conjunctival congestion and scarring, indicating a positive morphological effect.

Despite the morphological improvements, the injection did not significantly enhance tear secretion, as evidenced by minimal changes in Schirmer test values, suggesting that while 5-FU may help with surface appearance, it does not effectively increase tear production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Fluorouracil as a targeted lacrimal gland therapy for chronic Stevens-Johnson syndrome: A pilot study. Singh, S., Basu, S.[2023]

Intralesional 5-fluorouracil (5-FU) is considered safe for managing oculofacial scars, with the most common side effect being pain at the injection site, while serious adverse events were rare.

The existing studies suggest that 5-FU may be more effective than corticosteroid injections alone in reducing scar size and improving patient satisfaction, although high-quality randomized controlled trials specifically focused on oculofacial applications are still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Fluorouracil Management of Oculofacial Scars: A Systematic Literature Review. Bui, AD., Grob, SR., Tao, JP.[2021]

In a study of 63 glaucomatous eyes undergoing filtering surgery, the adjusted use of 5-fluorouracil (5-FU) injections led to successful surgical outcomes in a significant number of cases, with 87% success in aphakic eyes and 92% in eyes with previous failed filters.

While the approach of tailoring 5-FU dosage based on clinical response showed promise in reducing complications, such as conjunctival wound leaks and corneal toxicity, further validation through controlled randomized clinical trials is necessary to confirm its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjusting the dose of 5-fluorouracil after filtration surgery to minimize side effects. Weinreb, RN.[2022]

A 1-minute exposure to 5-Fluorouracil (5-FU) significantly inhibits the proliferation of fibroblasts in Tenon's capsule, showing similar effectiveness to the standard 5-minute application.

This study suggests that the optimal intraoperative exposure time for 5-FU could be reduced to just 1 minute, potentially improving surgical efficiency without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of varying 5-fluorouracil exposure duration on tenon's capsule fibroblasts. Merriman, MB., Mora, JS., Beaumont, BW., et al.[2019]

In a study of 29 eyes from 27 patients with high-risk glaucoma, 89.6% achieved controlled intraocular pressure after receiving subconjunctival injections of 5-Fluorouracil following filtering surgery, indicating its efficacy in managing difficult cases.

Despite its effectiveness, the treatment is associated with significant side effects, including conjunctival fistulas in 24% of cases and corneal epithelial breakdown in 69%, suggesting that while beneficial for high-risk patients, 5-Fluorouracil should not be used for standard glaucoma surgeries due to potential toxicity and complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[5-fluorouracil injection treatment after fistulating glaucoma operations]. Reinhard, T., Klüppel, M., Sundmacher, R.[2013]

A 60-year-old male with Granuloma Faciale showed excellent improvement after receiving a combination of 5-Fluorouracil (5FU) and Kenacort-A over three years, with a total of twenty injections.

The treatment allowed the patient to have long periods without therapy, lasting between nine to twelve months, suggesting that 5FU could be a viable option for clinicians treating Granuloma Faciale.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Laser Resistant Granuloma Faciale with Intralesional Triamcinolone acetonide and 5-Fluorouracil Combination Therapy. Norris, DL., Apikian, M., Goodman, GJ.[2020]

A new sustained release system for 5-fluorouracil (5-FU) using ethylene vinyl acetate copolymer (Elvax) was developed, allowing for controlled drug release over 14 days, which is crucial for preventing scar formation in glaucoma surgery.

The non-inflammatory properties of Elvax suggest that this delivery system could be a safer alternative for administering 5-FU during ophthalmologic procedures, enhancing its efficacy in inhibiting fibroblast proliferation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained release of 5-fluorouracil from ethylene acetate copolymer. Wyszynski, RE., Vahey, JB., Manning, L., et al.[2019]

In a study involving 62 patients undergoing initial trabeculectomy for open-angle glaucoma, adjunctive subconjunctival injections of 5-fluorouracil (5-FU) significantly lowered postoperative intraocular pressure (IOP) and reduced the need for antiglaucoma medications compared to a control group.

While 5-FU treatment was associated with a higher incidence of transient superficial punctate keratopathy, it ultimately increased the success rate of the surgery, with 94% of treated eyes achieving an IOP of 20 mmHg or lower, compared to 73% in the control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Fluorouracil in initial trabeculectomy. A prospective, randomized, multicenter study. Goldenfeld, M., Krupin, T., Ruderman, JM., et al.[2019]

A 9-month-old labradoodle survived accidental ingestion of 5-FU cream, demonstrating that timely intervention (including induced coma and mechanical ventilation) can effectively manage severe neurotoxic effects like status epilepticus.

Despite successful initial treatment, the dog experienced long-term adverse effects, including myelosuppression and progressive alopecia, highlighting the potential for lasting consequences even after survival from acute toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transient chemotherapy-induced alopecia after successful reversal of 5-fluorouracil myelosuppression and neurotoxicosis in a 9-month-old dog. Immelman, LM., Goodman, IH., Keller, N.[2022]

Subconjunctival injections of 5-fluorouracil (5-FU) in patients with failed filtering blebs after glaucoma surgery resulted in significant cytological changes, including squamous metaplasia and nuclear atypia in the conjunctival epithelium, observed in 60% of treated eyes.

The study involved 15 patients receiving 5-FU, and while changes were noted, the small sample size limited the ability to draw significant comparisons with other groups, including those treated with antiglaucomatous eyedrops and healthy controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term effects of subconjunctival injections of 5-fluorouracil on conjunctival epithelium. Simsek, T., Firat, P., Citirik, M., et al.[2013]

Citations

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iovs.arvojournals.org

iovs.arvojournals.org/article.aspx?articleid=2769137

Use of 5-Fluorouracil in Chalazion Treatment - IOVS

In 81 cases (64%), a single injection of 5-FU was successful in reducing lesion size and improving cosmetic appearance, resulting in patient satisfaction with ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02025023

Local 5-Fluorouracil Injection for the Treatment of Chalazia ...

Local injection of 5-fluorouracil into a chalazion (stye) is as effective as local injection of triamcinolone (steroid) and incision and curettage for treatment ...

3.

healio.com

healio.com/news/ophthalmology/20200707/combined-5futriamcinolone-reduces-chalazion-size

Combined 5-FU/triamcinolone reduces chalazion size

Researchers found a single injection of 5-FU/triamcinolone resulted in the successful treatment of 88 cases (64%).

4.

withpower.com

withpower.com/trial/phase-3-chalazion-11-2013-c9346

5-Fluorouracil Injection for Chalazion (CTS Trial)

The existing studies suggest that 5-FU may be more effective than corticosteroid injections alone in reducing scar size and improving patient satisfaction, ...

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institutionalrepository.aah.org

institutionalrepository.aah.org/advocategme/123/

Use of 5-fluorouracil in chalazion treatment

Use of 5-Fluorouracil in Chalazion Treatment. Investigative Ophthalmology & Visual Science. 2020;61(7):3973. Type. Abstract.

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pure.aah.org

pure.aah.org/en/publications/use-of-5-fluorouracil-in-chalazion-treatment

Use of 5-fluorouracil in chalazion treatment

Use of 5-fluorouracil in chalazion treatment. Investigative Ophthalmology & Visual Science. 2020 Jun 1. Moran, Joshua Michael ; Mohadjer, ...