Fluorouracil + Calcipotriene for Actinic Keratosis

Overseen By Mackenzie Wehner, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Topical steroids, Oral retinoids

Disqualifiers: Immunosuppression, Hypercalcemia, Skin cancer, others

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

Compensation: Varies

Number of Visits: 1

Duration: 2-3 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of two treatments for actinic keratosis, a skin condition with rough, scaly patches caused by excessive sun exposure. Researchers compare the effects of a skin cream called fluorouracil alone to a combination of fluorouracil and another cream, calcipotriene. Suitable candidates for this trial have 4 to 15 actinic keratoses on their head, neck, arm, or hand. Participants must begin treatment within a week of joining the trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications that could affect skin assessment, such as topical steroids, retinoids, and some oral medications like nicotinamide. If you're using any of these, you may need to stop them before participating.

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

Research has shown that a combination of fluorouracil and calcipotriene for treating actinic keratosis is generally well-tolerated by most patients. Earlier studies demonstrated that this combination significantly cleared skin lesions. However, about 47% of patients experienced local skin reactions, such as redness or irritation, which are usually mild and temporary.

Fluorouracil alone also has a strong safety record. Studies have found it effective and safe, with a low chance of lesions returning. Some patients might notice skin redness or discomfort, but these effects are usually temporary and part of the treatment process.

Both treatments show promise in clearing actinic keratosis while maintaining a good safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for actinic keratosis because they combine fluorouracil (5-FU) with calcipotriene, a vitamin D analog, which is a unique approach. While standard treatments like cryotherapy or using 5-FU alone focus on destroying abnormal cells, this combination therapy may enhance the immune response, potentially leading to more effective clearance of lesions. Additionally, calcipotriene may make the skin more receptive to 5-FU, potentially improving its efficacy. With the potential for better results in a shorter time, this combination could offer a promising alternative to existing therapies.

What evidence suggests that this trial's treatments could be effective for actinic keratosis?

This trial will compare the effectiveness of two treatment options for actinic keratosis. Participants in one arm will receive a combination of fluorouracil and calcipotriene. Studies have shown this combination effectively treats the skin condition by boosting the body's immune response and targeting abnormal cell growth. In one study, 81% of doctors found this combination more effective than fluorouracil alone, although some noted increased skin reactions. Participants in the other arm will receive fluorouracil by itself, which is also effective. Research shows it can clear up to 87% of lesions when combined with other treatments like light therapy. Both treatment options offer promise for those dealing with actinic keratosis. ^{1 4 6 7 8}

Who Is on the Research Team?

Mackenzie Wehner, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are not pregnant, have 4-15 visible actinic keratoses on their head, neck, arm, or hand. They must be able to start treatment within a week and sign consent. Those with other cancers that don't affect the trial's safety can join. People with hypercalcemia, vitamin D toxicity, allergies to the meds, nearby skin cancer or wounds, or recent use of certain skin treatments cannot participate.

Inclusion Criteria

Ability to start treatment within 1 week of enrollment

Ability to understand and the willingness to sign a written informed consent document

I am over 18, cannot become pregnant, and have 4-15 visible AKs on my head, neck, arm, or hand.

Exclusion Criteria

I have had high calcium levels in my blood.

Clinical evidence of vitamin D toxicity

Known allergy to any component of the medications or vehicle

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive topical 5-FU twice daily for 2-3 weeks

2-3 weeks

Standard-of-care clinical dermatology visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Calcipotriene
• Fluorouracil

Trial Overview The study tests two topical treatments for actinic keratosis: one group will apply fluorouracil alone while another will use fluorouracil combined with calcipotriene. The goal is to see which treatment is more effective in reducing sunspots on the skin.

How Is the Trial Designed?

Group I: Treatment with Fluorouracil and Calcipotriene Experimental Treatment 1 Intervention

Participants will screened and enrolled during a standard-of-care clinical dermatology visit. Participants will be randomized in between treatment with topical 5-FU twice daily for 2-3 weeks

Group II: Treatment with Fluorouracil Experimental Treatment 1 Intervention

Participants will screened and enrolled during a standard-of-care clinical dermatology visit. Participants will be randomized in between treatment with topical 5-FU twice daily for 2-3 weeks

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

A study involving 177 patients demonstrated that a microsphere-based formulation of 0.5% fluorouracil cream is effective in treating actinic keratosis (AK), with significant improvements in lesion counts and clearance compared to a vehicle control.

The treatment was found to be safe, with most patients experiencing only mild to moderate facial irritation, and efficacy increased with longer treatment durations of 1, 2, or 4 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective treatment of actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks. Weiss, J., Menter, A., Hevia, O., et al.[2013]

In a study involving 277 participants over 18 months, fluorouracil cream 0.5% was found to be safe and well-tolerated, with only 4 participants (7.4%) experiencing mild treatment-related adverse events.

The cream significantly reduced actinic keratosis (AK) lesions, achieving clearance rates of 39.8% on the face/anterior scalp and 79.1% on the lips after the first treatment cycle, with continued effectiveness observed during a second treatment cycle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorouracil cream 0.5% for actinic keratoses on multiple body sites: an 18-month open-label study. Stough, D., Bucko, AD., Vamvakias, G., et al.[2013]

A 1-week treatment with microsponge-based fluorouracil cream 0.5% significantly reduced actinic keratoses (AK) lesions compared to a vehicle control, demonstrating its efficacy (P<.001) in a study involving 356 participants.

The treatment was well-tolerated, with no serious adverse events reported, and only mild to moderate skin irritations experienced, indicating it is a safe option for patients with AKs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-week treatment with once-daily fluorouracil cream 0.5% in participants with actinic keratoses. Menter, A., Vamvakias, G., Jorizzo, J.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10680462/

Evaluating the Efficacy and Safety of 4% 5-Fluorouracil ... Treatment with 4% 5-fluorouracil cream was highly efficacious, safe, and prevented disease recurrence in approximately 27% of patients who achieved complete ...

2. medicaljournalssweden.se medicaljournalssweden.se/actadv/article/view/11954/37110

Evaluating the Efficacy and Safety of 4% 5-Fluorouracil ... This narrative review discusses data on 4% 5-fluorouracil cream to treat actinic keratosis, and provides the authors' expert opinion on issues ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S157210002400108X

Pre-treatment with topical 5-fluorouracil increases the ... Twelve weeks after treatment 87 % of all AKs cleared after 5-FU+dPDT compared to 74 % after dPDT alone (p<0.0001). For grade II AKs, the lesion response rate ...

4. link.springer.com link.springer.com/article/10.1007/s13555-025-01518-8

Efficacy of 5-Fluorouracil 4% Cream in the Treatment ... A retrospective study on 51 hyperkeratotic AKs in the context of field cancerization reported a complete response rate of 54.9% and a partial ...

5. derma.jmir.org derma.jmir.org/2023/1/e39988

Refusal of Retreatment With Topical 5-Fluorouracil Among ... Reducing unpleasant side effects of topical 5-Fluorouracil treatment for actinic keratosis: a randomized controlled trial. J Dermatolog Treat ...

6. medicaljournalssweden.se medicaljournalssweden.se/actadv/article/view/11954

Evaluating the Efficacy and Safety of 4% 5-Fluorouracil ... 4% 5-fluorouracil is associated with high efficacy, a low level of recurrence and a satisfactory safety profile.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06461442

Efficacy and Safety of Cryotherapy Versus 5-Fluorouracil in ... The goal of this clinical trial is to compare the effectiveness and safety of two treatments-cryotherapy and 5-Fluorouracil (5-FU)-for actinic keratosis, a ...

8. link.springer.com link.springer.com/article/10.1007/s13555-024-01336-4

A Post-Hoc Analysis of Two Randomised Clinical Trials The study investigated whether the severity of skin reactions from 5-fluorouracil 4% cream resulted in better lesion clearance 4 weeks after ...