5-Fluorouracil + Calcipotriene Cream for Skin Cancer

Recruiting at 1 trial location

Overseen By Frederick Gibson, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Boston University

Disqualifiers: Immunosuppression, Genetic disorders, Pregnancy, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1-4 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new cream, combining 5-fluorouracil (a chemotherapy drug) and calcipotriene (a form of vitamin D), can treat certain low-risk skin cancers more quickly than the usual treatment. These skin cancers include superficial basal cell carcinoma and squamous cell carcinoma in situ. Participants will use either the new combination cream for 7 to 14 days or the standard 5-fluorouracil cream for 28 days. Individuals with untreated skin cancers on areas like the scalp, trunk, or face, who are not candidates for surgery, might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that a cream combining 5-fluorouracil and calcipotriene effectively treats actinic keratoses, early forms of skin cancer. In previous studies, this cream cleared 86.7% of these spots after just four days of use. It also appears to reduce the risk of new skin cancers over three years, indicating it is a well-tolerated treatment option.

The FDA has already approved 5-fluorouracil cream alone for treating superficial basal cell carcinoma. Dermatologists often use it for certain skin cancers, including squamous cell carcinoma in situ, suggesting it is generally safe for these conditions.

Overall, past studies have well-received these treatments, offering reassurance about their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a potentially quicker and more effective approach to treating skin cancer. Unlike the standard of care, which typically involves prolonged application of 5-fluorouracil alone, the combination of 5-fluorouracil with calcipotriene cream is applied for just 7 to 14 days. This combo not only reduces treatment time but also enhances the immune response against cancer cells due to calcipotriene's role in activating vitamin D pathways. This dual-action approach could lead to faster and improved outcomes for patients.

What evidence suggests that this trial's treatments could be effective for skin cancer?

Research has shown that a cream combining 5-fluorouracil and calcipotriene effectively treats precancerous skin conditions like actinic keratosis. In this trial, participants in one arm will receive this combination cream. The cream aids the immune system in combating abnormal skin cell growth and reduces the risk of skin cancer. One study found that using this cream reduced skin lesions by about 87.8%, compared to only 26.3% with another treatment. Another study found that this combination might help prevent certain types of skin cancer, especially on the face and scalp. By targeting precancerous cells, this cream offers a promising way to lower skin cancer risks. ^{1 4 5 6 7}

Who Is on the Research Team?

Bilal Fawaz, MD

Principal Investigator

Dermatology, Boston University School of Medicine

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• 5-Fluorouracil
• Calcipotriene

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.

How Is the Trial Designed?

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 European Union, United States, Canada, Japan for the following indications:

Approved in European Union as 5-FU for:

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

Approved in United States as 5-FU for:

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

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+

Published Research Related to This Trial

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]

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]

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]

In a study involving seven patients with advanced squamous cell carcinoma of the skin, six patients showed positive responses to treatment with cisplatin and 5-fluorouracil, including three complete responses and three partial responses.

One patient remained alive and disease-free two years after treatment, suggesting that the combination of cisplatin and 5-FU is a promising and effective regimen for this type of cancer, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin and 5-fluorouracil for advanced locoregional and metastatic squamous cell carcinoma of the skin. Khansur, T., Kennedy, A.[2022]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11499312/

Calcipotriol and 5-Fluorouracil Combination Therapy for ... The combination of 5-FU and calcipotriol effectively treats actinic keratosis by enhancing the immune response and targeting cell overgrowth.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05699603

Study Details | NCT05699603 | Testing the Efficacy of ... This phase IIA study evaluates the effects of calcipotriene plus 5- fluorouracil immunotherapy for skin cancer prevention in organ transplant recipients.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27869649/

Randomized trial of calcipotriol combined with 5-fluorouracil ... Four-day application of calcipotriol plus 5-FU versus Vaseline plus 5-FU led to an 87.8% versus 26.3% mean reduction in the number of actinic ...

4. ajmc.com ajmc.com/view/combination-immunotherapy-offers-new-pathway-for-skin-cancer-prevention

Combination Immunotherapy Offers New Pathway for Skin ... A topical treatment combining calcipotriol and 5-FU shows promise in reducing premalignant lesions and lowering skin cancer risk by activating Th2 immunity.

5. insight.jci.org insight.jci.org/articles/view/125476

Skin cancer precursor immunotherapy for squamous cell ... In contrast, our results suggest that calcipotriol plus 5-FU treatment is effective in preventing SCC development on the face and scalp within 3 ...

6. jaad.org jaad.org/article/S0190-9622(24)03122-0/abstract

Combined topical 5-fluorouracil and calcipotriene ... Prior studies demonstrated 4 days of twice daily 5FU/C resulted in 86.7% clearance of actinic keratoses and reduced 3-year skin cancer formation ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03370406

Intralesional 5-Fluorouracil (5FU), Topical Calcipotriene ... This clinical trial proposes to evaluate a relatively unexplored approach to treatment of squamous cell carcinoma (SCC) on the lower extremities.