5-Fluorouracil + Calcipotriene Cream for Skin Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Bilal Fawaz, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Boston University

Disqualifiers: Immunosuppression, Genetic disorders, Pregnancy, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial compares a standard cancer-killing cream with a new, potentially more effective cream. It targets patients with less aggressive skin cancers. The new cream might work better by combining two ingredients to kill cancer cells and prevent new ones from forming.

Do I need to stop my current medications for this trial?

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 5-Fluorouracil + Calcipotriene Cream for skin cancer?

Research shows that the combination of calcipotriol and 5-fluorouracil is effective in treating actinic keratosis, a skin condition that can lead to squamous cell carcinoma, a type of skin cancer. Additionally, 5-fluorouracil has been used successfully in treating non-melanoma skin cancers. ^{1 2 3 4 5}

Is the combination of 5-Fluorouracil and Calcipotriene cream safe for use in humans?

Topical 5-Fluorouracil (5-FU) can cause local skin reactions like redness, pain, and crusting, and in rare cases, distant skin reactions. However, it is generally considered safe for treating certain skin conditions, and combining it with Calcipotriene has been used effectively for skin cancer precursors. ^{1 5 6 7 8}

How is the drug 5-Fluorouracil + Calcipotriene Cream unique for skin cancer treatment?

The combination of 5-Fluorouracil and Calcipotriene is unique because it acts as an immunotherapy for actinic keratosis, a precursor to squamous cell carcinoma, potentially preventing skin cancer by enhancing the immune response, which is different from traditional treatments that primarily focus on direct destruction of cancer cells. ^{1 3 4 5 7}

Research Team

Bilal Fawaz, MD

Principal Investigator

Dermatology, Boston University School of Medicine

Eligibility Criteria

This trial is for English-speaking adults with low-risk skin cancers (sBCC or SCCis) on certain body parts, who haven't had treatment yet and aren't good candidates for surgery. They must be willing to follow the study plan and attend follow-ups. Women of childbearing age need a negative pregnancy test before starting and must use birth control during the study.

Inclusion Criteria

I am willing to follow all study requirements and attend all follow-up visits.

English-speaking

If a woman is of childbearing potential, the participant must be willing to take a pregnancy test before starting treatment and be on some form of birth control while receiving treatment. Birth control can include abstinence, oral contraceptive pill, intrauterine device, implanted birth control device, birth control patch, or the vaginal ring. The patient does not need to be on any form of birth control after they end therapy.

Exclusion Criteria

You have a very high risk of dying at the beginning of the study.

I have lesions around my eye area.

I have a genetic condition that increases my risk for skin cancer.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 5-fluorouracil cream for 28 days or a combination cream of 5-fluorouracil and calcipotriene for 7-14 days

1-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with visits every 6 months for 3 years

3 years

Biannual visits (in-person)

Treatment Details

Interventions

• 5-Fluorouracil (Anti-metabolites)
• Calcipotriene (Other)

Trial Overview The trial compares two creams: one with just 5-fluorouracil, an FDA-approved treatment, against a mix of 5-fluorouracil and calcipotriene. The goal is to see if the combo cream can clear cancer in a shorter time (7-14 days). Participants will be checked over three years to see if their skin cancer has been treated successfully.

Participant Groups

Group I: Combination cream of 5-fluorouracil and calcipotriene Experimental Treatment 1 Intervention

Participants randomized to this group will receive treatment with the combination cream consisting of 5-fluorouracil and calcipotriene twice a day for 7 days and the treatment can be extended to 14 days based on evaluation at 7 days.

Group II: 5-fluorouracil cream Active Control 1 Intervention

Participants randomized to this group will receive treatment with 5-fluorouracil cream twice a day for 28 days.

5-Fluorouracil is already approved in Canada, Japan for the following indications:

Approved in Canada as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer

Approved in Japan as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Boston University

Lead Sponsor

Trials

494

Recruited

9,998,000+

Sophie Kornowski

Boston University

Chief Executive Officer since 2022

MBA from the University of Chicago, Doctorate in Pharmacy from Paris Descartes University

Dr. Patrizia Cavazzoni

Boston University

Chief Medical Officer

MD from McGill University

Findings from Research

A short 4-day treatment with topical calcipotriol plus 5-fluorouracil (5-FU) significantly reduced the incidence of squamous cell carcinoma (SCC) in participants over a 3-year follow-up, with only 7% developing SCC compared to 28% in the control group.

The treatment also induced a strong immune response, evidenced by the formation of tissue-resident memory T (Trm) cells in the skin, which correlated with better long-term protection against SCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. Rosenberg, AR., Tabacchi, M., Ngo, KH., et al.[2020]

The 0.5% fluorouracil cream was more effective than the 5% cream in reducing the absolute number of actinic keratosis (AK) lesions, with a decrease from 11.3 to 2.5 lesions compared to a decrease from 10.3 to 4.2 lesions with the 5% cream.

Patients preferred the 0.5% cream due to its better tolerability, easier application, and once-daily dosing, despite both creams causing some facial irritation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy and tolerability of 0.5% fluorouracil cream and 5% fluorouracil cream applied to each side of the face in patients with actinic keratosis. Loven, K., Stein, L., Furst, K., et al.[2019]

Topical 5-fluorouracil 5% cream was effectively used to treat two patients with extensive non-melanoma skin cancer, resulting in the clearance of the majority of lesions.

Despite the treatment's effectiveness, patients experienced pain and secondary infections as side effects, but no detectable serum levels of the drug were found, indicating a favorable safety profile for this application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total body topical 5-fluorouracil for extensive non-melanoma skin cancer. van Ruth, S., Jansman, FG., Sanders, CJ.[2018]

A new varnish combining 5% 5-fluorouracil and salicylic acid was tested on 20 patients with solar keratoses, showing effective treatment with only one to five applications needed for facial lesions to achieve apparent cure.

While facial lesions responded well, hand lesions were more resistant, requiring up to nine applications for successful treatment, indicating variability in treatment response based on lesion location.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of solar keratoses with a 5-fluorouracil and salicylic acid varnish. Goncalves, JC.[2019]

A new scale was developed to reliably measure the toxicity of topical 5% 5-fluorouracil, focusing on parameters like erythema and crusting, which are common side effects.

The scale demonstrated high reliability with an intraclass correlation of 0.82 among 13 raters, indicating it can be effectively used by both dermatologists and non-dermatologists to assess treatment toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring the severity of topical 5-fluorouracil toxicity. Korgavkar, K., Firoz, EF., Xiong, M., et al.[2017]

A 63-year-old man developed a seborrheic dermatitis-like reaction on his face after using topical 5-fluorouracil on his arms for 7 days, indicating that distant skin reactions can occur with this medication.

The facial dermatitis resolved after stopping the treatment and recurred upon reapplication, confirming a direct link between the drug and the adverse effect, although the exact mechanism behind this distant reaction remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Application of 5-Fluorouracil Associated with Distant Seborrheic Dermatitis-like Eruption: Case Report and Review of Seborrheic Dermatitis Cutaneous Reactions after Systemic or Topical Treatment with 5-Fluorouracil. Werbel, T., Cohen, PR.[2020]

Topical 5-fluorouracil (5-FU) 5% ointment is a safe and effective non-invasive treatment for non-syndromic multifocal basal cell carcinoma (BCC), as demonstrated in a case study of a 55-year-old male with multiple lesions, where significant improvement was observed within 8 weeks.

This treatment offers a less invasive alternative to traditional surgical methods, with the patient showing no recurrence of BCC after 6 months and achieving clear margins post-treatment, highlighting its potential as a convenient and effective option for managing larger or recurrent lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical 5% 5-fluorouracil in the treatment of multifocal basal cell carcinoma of the face: A novel chemotherapeutic approach. Naik, MP., Mehta, A., Abrol, S., et al.[2017]

References

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

Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. [2020]

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

Cisplatin and 5-fluorouracil for advanced locoregional and metastatic squamous cell carcinoma of the skin. [2022]

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

Evaluation of the efficacy and tolerability of 0.5% fluorouracil cream and 5% fluorouracil cream applied to each side of the face in patients with actinic keratosis. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Total body topical 5-fluorouracil for extensive non-melanoma skin cancer. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Treatment of solar keratoses with a 5-fluorouracil and salicylic acid varnish. [2019]

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

Measuring the severity of topical 5-fluorouracil toxicity. [2017]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Topical Application of 5-Fluorouracil Associated with Distant Seborrheic Dermatitis-like Eruption: Case Report and Review of Seborrheic Dermatitis Cutaneous Reactions after Systemic or Topical Treatment with 5-Fluorouracil. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Topical 5% 5-fluorouracil in the treatment of multifocal basal cell carcinoma of the face: A novel chemotherapeutic approach. [2017]