Topical Diclofenac for Non-melanoma Skin Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must not be taking: Corticosteroids, NSAIDs, Anticoagulants, others

Disqualifiers: Invasive cancer, Transplant, Photosensitivity, others

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: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a topical medication, diclofenac (a nonsteroidal anti-inflammatory drug), can prevent non-melanoma skin cancers by targeting specific molecules in the skin. Participants will apply the medication or a placebo to a small, sun-exposed area on their arm daily for 30 days. The trial seeks individuals who have previously had non-melanoma skin cancer and can commit to using the treatment as directed. The research aims to determine if diclofenac can effectively reverse skin changes that lead to cancer. As a Phase 2 trial, this study focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to stop using certain medications, including topical medications on areas of actinic damage and chronic NSAIDs or COX-2 inhibitors, except for low-dose aspirin. You can use acetaminophen for pain if needed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that topical diclofenac is generally safe for use. Studies have found that the FDA has approved it for treating actinic keratoses, early-stage skin lesions that can lead to cancer. This approval indicates its safety for skin treatments. Most people who used diclofenac for actinic keratoses experienced mild side effects, such as redness or itching at the application site. Serious side effects were rare. These findings suggest that diclofenac is usually safe for skin use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-melanoma skin cancer?

Unlike the standard treatments for non-melanoma skin cancer, which often include surgical removal or topical chemotherapy, diclofenac offers a unique approach. Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) that works by reducing inflammation and potentially inhibiting cancer cell growth. Its topical application directly to the skin is less invasive compared to surgery and may have fewer side effects than traditional chemotherapy. Researchers are excited about this treatment because it could provide a simpler, more patient-friendly option for managing non-melanoma skin cancers.

What evidence suggests that diclofenac might be an effective treatment for non-melanoma skin cancer?

Research has shown that diclofenac cream can help treat certain skin conditions. For instance, one study found that applying diclofenac to sun-damaged skin reduced the number of tumors. Another study discovered that diclofenac cleared a specific type of skin cancer in about 64% of patients. Diclofenac improves the function of damaged skin and boosts the immune response. It has also been shown to keep skin clear for a year after treating pre-cancerous spots. In this trial, participants will receive either diclofenac or a placebo to evaluate its effectiveness in preventing certain non-melanoma skin cancers. ^{1 3 6 7 8}

Who Is on the Research Team?

Craig Elmets, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for adults with good performance status, not undergoing other cancer treatments or major surgery within the last month. They must avoid certain medications and be willing to stop using topical products on damaged skin areas, except moisturizers and sunscreens. Women of childbearing age should use contraception and have a negative pregnancy test.

Inclusion Criteria

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

Willing and able to participate for the full duration of the study

My blood, liver, and kidney tests are within normal ranges.

Exclusion Criteria

Uncontrolled concurrent illness including ongoing or active infection, psychiatric illness/social situations that would limit compliance with study requirements or other underlying serious medical condition which, in the investigator's opinion, might preclude study participation

I haven't had major surgery, chemotherapy, or other cancer treatments except for early-stage skin cancer in the last 4 weeks.

I use certain nasal sprays, aspirin over 100mg/day, NSAIDs, or COX-2 inhibitors more than 3 times a week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive topical diclofenac or placebo applied daily for 30 days to evaluate the effect on skin cancer biomarkers

4 weeks

1 visit (in-person) for initial application instructions

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on biomarker reduction and actinic keratoses

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Diclofenac
• Placebo

Trial Overview The study tests if diclofenac cream can prevent non-melanoma skin cancers by reversing biomarkers in the skin. It's a small-scale trial at University of Alabama involving 24 patients to find the best dose. Diclofenac is FDA-approved for other uses but not yet for this one.

How Is the Trial Designed?

Group I: diclofenac once daily Active Control 1 Intervention

Topical diclofenac, will will be applied onto the skin of one arm, every day for 30 days. Enough medication will be used to cover an area of approximately 4 square inches( a 2 inch by 2 inch square). The medications will come in a tube. The medications will be applied to the same sun exposed site on the arm every day. The research team will provide instructions for the correct application of the treatment.

Group II: placebo Placebo Group 1 Intervention

The topical medication will will be applied onto the skin of one arm, once daily for 30 days. Enough placebo will be used to cover an area of approximately 4 square inches( a 2 inch by 2 inch square). The placebo will come in a tube. The placebo will be applied to the same sun exposed site on the arm every day. The research team will provide instructions for the correct application of the treatment.

Diclofenac is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Voltaren for:

• Ankylosing Spondylitis
• Aseptic Necrosis
• Back Pain
• Chronic Pain
• Frozen Shoulder
• Headache
• Migraine
• Muscle Pain
• Osteoarthritis
• Pain
• Period Pain
• Rheumatoid Arthritis
• Sciatica
• Spondyloarthritis

Approved in European Union as Voltaren for:

• Osteoarthritis
• Rheumatoid Arthritis
• Ankylosing Spondylitis
• Migraine
• Pain
• Dysmenorrhea

Approved in Canada as Voltaren for:

• Osteoarthritis
• Rheumatoid Arthritis
• Ankylosing Spondylitis
• Migraine
• Pain
• Dysmenorrhea

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Diclofenac (VOLTAREN) is effective for various conditions treated with NSAIDs, showing good tolerability and a favorable balance between COX-2 and COX-1 inhibition, which may reduce side effects.

The drug is available in multiple forms and has a long history of use, but caution is advised for patients at risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Voltaren--the gold standard]. Babić-Naglić, D.[2013]

Solaraze gel, which contains 3% diclofenac, has been used since 2001 as a topical treatment for actinic keratoses and is commonly utilized in dermatology.

While undesirable effects from Solaraze gel are considered rare, they can include skin reactions such as pruritus, paresthesia, and contact dermatitis, with recent reports highlighting cases of contact dermatitis linked to diclofenac and other allergens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photoallergic contact dermatitis from topical diclofenac in Solaraze gel. Kowalzick, L., Ziegler, H.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3564442/

Preventative topical diclofenac treatment differentially ... We demonstrate that prolonged, topical diclofenac treatment of chronically UVB-damaged skin effectively reduced tumor multiplicity in both sexes.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0190962216001304

The effect of topical diclofenac 3% and calcitriol 3 μg/g on ... This phase II trial provides evidence that topical diclofenac has the potential to clear sBCC, with complete histologic tumor regression in 64.3% (9 of 14) and ...

3. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00605/full

Topical Diclofenac Reprograms Metabolism and Immune ... Diclofenac normalizes metabolism, immune cell infiltration and function in AK lesions, suggesting a novel mechanism of action.

4. jcadonline.com jcadonline.com/long-term-follow-up-of-diclofenac-sodium-3-in-25-hyaluronic-acid-gel-for-actinic-keratosis-one-year-evaluation/

Long-term Follow up of Diclofenac Sodium 3% in 2.5% ... In conclusion, diclofenac sodium 3% gel in this study produced sustained clearance of the majority of AK lesions for at least one year post-treatment.

5. ar.iiarjournals.org ar.iiarjournals.org/content/33/8/3033

Combination Chemoprevention with Diclofenac ... Conclusion: Potentially, non-melanoma skin cancer in humans may be prevented with these agents with few adverse effects. Therefore, clinical studies are needed ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3132090/

Diclofenac gel in the treatment of actinic keratoses - PMC Imiquimod upregulates cell-mediated immunity, which is effective against viruses and tumors, and has been approved for treating actinic keratoses and ...

7. mdpi.com mdpi.com/2218-0532/93/3/34

Novel Research Regarding Topical Use of Diclofenac in ... Diclofenac is now approved for the topical treatment of actinic keratoses (AK), pre-malignant entities that have the risk of transformation into skin carcinomas ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1470211824027465

Non-melanoma skin cancer Non-melanoma skin cancer (NMSC) comprises basal cell carcinoma (BCC) and squamous cell carcinoma, together with a host of rare tumours.