5-Fluorouracil Injection for Chalazion

(CTS Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Matthew M Zhang, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: University of Washington

Disqualifiers: Chalazia less than one month

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial compares different treatments for eyelid lumps called chalazia. The treatments include medicine injections or minor surgery. The goal is to see which method best reduces or removes these lumps. Injections have been used effectively in treating chalazia, showing high success rates in previous studies.

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.

What data supports the effectiveness of the drug 5-fluorouracil injection for treating chalazion?

Research shows that 5-fluorouracil (5-FU) has been used successfully in eye-related treatments, such as improving outcomes in glaucoma surgeries and treating severe dry eye disease. This suggests it may have potential benefits for other eye conditions like chalazion. ^{1 2 3 4 5}

Is 5-Fluorouracil generally safe for humans?

5-Fluorouracil (5-FU) is used in various treatments, including skin cancer and eye surgeries, and is generally considered safe when used as directed. Some studies show that it can cause mild skin irritation, but formulations like bioadhesive gels can reduce this risk. However, it can be toxic if ingested, especially in animals. ^{6 7 8 9 10}

How does the drug 5-fluorouracil injection differ from other treatments for chalazion?

5-fluorouracil injection is unique because it is typically used to inhibit cell growth and scar formation, which is not a common approach for treating chalazion. This drug is often used in eye surgeries to prevent excessive tissue growth, suggesting a novel mechanism for addressing chalazion by potentially reducing inflammation and promoting healing. ^{3 4 5 7 11}

Research Team

Matthew M Zhang, MD

Principal Investigator

University of Washington Eye Institute

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• 5-fluorouracil Injection (Anti-metabolites)
• Triamcinolone Acetonide (Corticosteroid)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Timothy H. Dellit

University of Washington

Chief Executive Officer since 2023

MD from University of Washington

Dr. Anneliese Schleyer

University of Washington

Chief Medical Officer since 2023

MD, MHA

Findings from Research

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]

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]

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 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 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]

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 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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Short-term effects of subconjunctival injections of 5-fluorouracil on conjunctival epithelium. [2013]

3. Germany pubmed.ncbi.nlm.nih.gov

[5-fluorouracil injection treatment after fistulating glaucoma operations]. [2013]

4. Australia pubmed.ncbi.nlm.nih.gov

Effects of varying 5-fluorouracil exposure duration on tenon's capsule fibroblasts. [2019]

5. India pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

5-Fluorouracil in initial trabeculectomy. A prospective, randomized, multicenter study. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Sustained release of 5-fluorouracil from ethylene acetate copolymer. [2019]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

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

9. United States pubmed.ncbi.nlm.nih.gov

5-Fluorouracil Management of Oculofacial Scars: A Systematic Literature Review. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Transient chemotherapy-induced alopecia after successful reversal of 5-fluorouracil myelosuppression and neurotoxicosis in a 9-month-old dog. [2022]

11. India pubmed.ncbi.nlm.nih.gov

Treatment of Laser Resistant Granuloma Faciale with Intralesional Triamcinolone acetonide and 5-Fluorouracil Combination Therapy. [2020]