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

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This research study will test how well one topical medications work to prevent the development of non-melanoma skin cancers by reversing certain biomarkers in the skin. This study is also looking at the optimal dose of a medication in a small number of people. Biomarkers are molecules that are found in the body and inside of cells. Some biomarkers are associated with specific diseases such as skin cancer. In this study, one topical medication will be evaluated; diclofenac. Diclofenac and is approved by the Food and Drug Administration (FDA) for other uses. 24 patients will be enrolled in this study by University of Alabama at Birmingham.

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 topical diclofenac safe for use in humans?

Topical diclofenac, used in products like Solaraze gel, is generally safe for humans but can cause mild to moderate side effects such as dry skin, rash, and itching at the application site. Rarely, it may cause contact dermatitis (skin irritation) in some individuals. ^{1 2 3 4 5}

How does the drug diclofenac differ from other treatments for non-melanoma skin cancer?

Diclofenac is unique because it is applied topically (directly on the skin) and has shown effectiveness in treating actinic keratosis, a common precancerous skin condition. Unlike some other treatments, it can be used at home, which may be more convenient for patients who have difficulty visiting a clinic for therapies like photodynamic therapy. ^{3 6 7 8 9}

What evidence supports the effectiveness of the drug diclofenac for treating non-melanoma skin cancer?

Research shows that diclofenac is effective in treating actinic keratosis, a common precancerous skin condition, with studies indicating a significant reduction in lesions after treatment. ^{2 3 6 8 9}

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

Phase IIB Randomized Study of Topical Difluoromethylornithine and Topical Diclofenac on Sun-Damaged Skin of the Forearm. [2018]

2. Croatia pubmed.ncbi.nlm.nih.gov

[Voltaren--the gold standard]. [2013]

3. Croatia pubmed.ncbi.nlm.nih.gov

Using photodynamic therapy to estimate effectiveness of innovative combined diclofenac and tazaroten therapy of disseminated actinic keratosis. [2016]

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

Topical treatment strategies for non-melanoma skin cancer and precursor lesions. [2018]

5. Denmark pubmed.ncbi.nlm.nih.gov

High death rate in mice treated topically with diclofenac. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Photoallergic contact dermatitis from topical diclofenac in Solaraze gel. [2013]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Voltaren gel in the combined treatment of patients with psoriatic arthritis]. [2013]

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

Phase IV, open-label assessment of the treatment of actinic keratosis with 3.0% diclofenac sodium topical gel (Solaraze). [2013]

9. England pubmed.ncbi.nlm.nih.gov

Topical treatment with diclofenac, calcipotriol (vitamin-D3 analog) and difluoromethylornithine (DFMO) does not prevent nonmelanoma skin cancer in mice. [2014]