Diphencyprone + Immunotherapy for Skin Cancer

Overseen By Vicky K Wong, MS, CCRC

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nicholas Gulati

Must be taking: PD-1, PD-L1 inhibitors

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: HIV, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat skin cancer that has spread to the skin, using a combination of topical diphencyprone (DPCP) and immune checkpoint inhibitors, which help the immune system attack cancer cells. The main goal is to assess how these treatments affect the genes in immune and cancer cells and to understand any side effects. Suitable participants have skin cancer that has spread to at least three spots on the skin and plan to receive certain immune therapy drugs as part of their usual treatment. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as corticosteroids, immunosuppressants, and any other drugs that might affect the study's outcome. It's best to discuss your current medications with the study team to see if they are allowed.

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

Research shows that diphencyprone (DPCP) can cause skin irritation and allergic reactions. One study used DPCP for ten weeks with a small group of people, and half reported the treatment as safe and manageable. Although DPCP is not yet approved for conditions like alopecia areata, it is under study for its potential benefits.

Researchers are exploring how well DPCP works with immune checkpoint inhibitors, a type of cancer treatment. As the study begins, the primary goal is to assess the safety of using these treatments together. At this stage, researchers focus on safety and side effects to guide future studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using diphencyprone (DPCP) for skin cancer because it introduces a unique way of engaging the immune system to fight the disease. Unlike traditional treatments like surgery, radiation, or chemotherapy, which directly target and remove cancer cells, DPCP acts by stimulating an immune response in the skin. This topical ointment challenges the body's defenses to recognize and attack cancer cells, potentially offering a less invasive and more targeted approach. Additionally, when combined with immune checkpoint inhibitors, DPCP could amplify the immune response, providing a powerful one-two punch in tackling skin cancer.

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

Research has shown that diphencyprone (DPCP) can help treat skin cancer that has spread to the skin, known as cutaneous metastases. Studies have found that applying DPCP to the skin can help manage the disease, with some patients experiencing stable cancer, meaning it did not worsen. In this trial, participants will receive DPCP treatment. Additionally, DPCP has shown promise when used with immune therapies that help the body fight cancer. Researchers are exploring whether combining DPCP with immune checkpoint inhibitors, which boost the immune system, enhances effectiveness. These findings suggest that DPCP might be effective against skin cancer, especially when used with other treatments. ^{2 6 7 8 9}

Who Is on the Research Team?

Philip Friedlander, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Nicholas Gulati, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

Adults with skin cancer and at least three cutaneous (skin) metastases, who are planned to receive FDA-approved PD-1 or PD-L1 immune checkpoint inhibitors. They must be in a relatively stable condition (ECOG 0-2), able to consent, and use contraception. Excluded are those on certain other treatments like steroids, allergic to DPCP components, pregnant/nursing women, individuals with HIV or specific lymph node removals affecting the treatment area.

Inclusion Criteria

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

I agree to use birth control during and for 90 days after the study.

My next treatment is an FDA-approved immune therapy.

Exclusion Criteria

I do not have skin conditions or diseases that could interfere with the treatment.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I am not on a combination of immune checkpoint inhibitors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive topical DPCP twice weekly for 12 weeks in combination with PD-1 or PD-L1 immune checkpoint inhibition

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Diphencyprone (DPCP)
• Immune Checkpoint Inhibition

Trial Overview The study is testing the effect of a topical drug called Diphencyprone (DPCP) applied twice weekly for 12 weeks alongside standard immune checkpoint inhibitors. It aims to observe changes in gene expression in treated skin cancer metastases and document any adverse events from this combination therapy.

How Is the Trial Designed?

Group I: Diphencyprone (DPCP) Experimental Treatment 1 Intervention

0.4% and 0.04% ointment

Who Is Running the Clinical Trial?

Nicholas Gulati

Lead Sponsor

Trials

2

Recruited

120+

Published Research Related to This Trial

Immune checkpoint inhibitors like pembrolizumab can effectively treat advanced lung adenocarcinoma but may lead to significant skin-related side effects, such as diffuse bullous lichenoid dermatitis affecting over 50% of the body.

In these two reported cases, the skin reactions were managed successfully with oral dexamethasone while allowing for minimal interruption of pembrolizumab treatment, suggesting a potentially safer and more conservative management strategy than current guidelines recommend.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Outpatient Management of Diffuse Photosensitive Bullous Dermatitis Following Pembrolizumab Therapy. Penny, C., Nath, N., Kheterpal, M.[2022]

Immune checkpoint inhibitors, which activate T-cells to fight cancer, have a unique safety profile characterized by immune-related adverse events, particularly affecting the skin, with over a third of patients experiencing dermatological issues.

Common skin reactions include mild to moderate rashes and pruritus, but more serious conditions like autoimmune diseases can occur, necessitating thorough dermatological evaluation and management for severe or unusual symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dermatologic toxicities of immune checkpoint inhibitors]. Sibaud, V., Boulinguez, S., Pagès, C., et al.[2018]

Anti-PD-1/PD-L1 therapies, like MK-3475, effectively activate the immune system against cancer by blocking tumor evasion mechanisms, with side effects generally being mild and manageable.

In three reported cases, patients developed lichenoid dermatitis characterized by T-cell infiltrates, but the rashes were mild enough to allow continued treatment, indicating a tolerable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lichenoid dermatitis in three patients with metastatic melanoma treated with anti-PD-1 therapy. Joseph, RW., Cappel, M., Goedjen, B., et al.[2022]

In a study of 15 patients with in-transit or unresectable melanoma treated with DPCP, 13% achieved a complete response and 27% had a partial response, indicating potential efficacy of DPCP in this patient population.

DPCP treatment was associated with manageable toxicity, primarily blisters, and may serve as a viable option to delay the need for systemic therapy in patients who are ineligible for surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical immunotherapy with diphencyprone (DPCP) for in-transit and unresectable cutaneous melanoma lesions: an inaugural Canadian series. Yeung, C., Petrella, TM., Wright, FC., et al.[2022]

In a study involving 16 melanoma patients treated with topical diphencyprone, 37.5% achieved a complete response and 25% had a partial response, indicating its potential efficacy as a local immunotherapy.

The treatment was well tolerated with manageable local toxicity, suggesting that diphencyprone could be a viable option for patients with cutaneous melanoma metastases, particularly in advanced cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diphencyprone as a therapeutic option in cutaneous metastasis of melanoma. A single-institution experience. Gibbons, IL., Sonagli, M., Bertolli, E., et al.[2023]

A patient with metastatic melanoma developed a widespread bullous pemphigoid-like skin reaction 8 months after starting treatment with the PD-1 inhibitor pembrolizumab, indicating that severe skin toxicity can occur long after initiating therapy.

Despite requiring prolonged corticosteroid treatment for the skin reaction, the efficacy of the PD-1 inhibitor in treating advanced melanoma was not compromised, suggesting that immunosuppression may not interfere with the drug's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late presentation of generalised bullous pemphigoid-like reaction in a patient treated with pembrolizumab for metastatic melanoma. Parakh, S., Nguyen, R., Opie, JM., et al.[2018]

Immune checkpoint inhibitors, which help the immune system fight cancer, can lead to various skin-related side effects, with Bullous Pemphigoid being a rare but serious condition that significantly affects patients' quality of life.

The article reviews the characteristics and timing of Bullous Pemphigoid onset after treatment with immune checkpoint inhibitors, highlighting the need for awareness and appropriate management of this adverse event.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective, Single-Institution Experience of Bullous Pemphigoid as an Adverse Effect of Immune Checkpoint Inhibitors. Shalata, W., Weissmann, S., Itzhaki Gabay, S., et al.[2022]

PD-1 inhibitors, like pembrolizumab, are effective cancer treatments but can cause skin side effects, such as lichenoid drug eruptions, which typically improve with topical steroids without needing to stop the medication.

In a case study of an 84-year-old woman, her lichenoid eruption did not respond to standard treatments and required stopping pembrolizumab and using methotrexate for resolution, highlighting the need for careful management of severe skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steroid-Refractory Lichenoid Eruption Associated with Pembrolizumab in a Patient with Non-Small Cell Lung Cancer. Kou, L., Agarwal, S., Miceli, A., et al.[2023]

Combination immunotherapy using durvalumab and tremelimumab, which target PD-1 and CTLA-4 respectively, is being investigated for treating metastatic melanoma and non-small cell lung cancer.

A case of bullous pemphigoid, a serious skin condition, was reported as a dermatologic toxicity in a patient receiving these immunotherapies, highlighting the need for monitoring skin-related side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bullous Pemphigoid Associated With a New Combination Checkpoint Inhibitor Immunotherapy Fontecilla, NM., Khanna, T., Bayan, CY., et al.[2022]

Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers in the U.S., making photoprotection and early detection crucial for prevention, alongside the use of agents like retinoids to reduce the risk of progression from premalignant cells.

Recent studies show that newer nonsurgical therapies, such as interferon, imiquimod, and photodynamic therapy, are effective in treating superficial nonmelanoma skin cancers and can significantly lower morbidity and mortality rates, providing alternatives to traditional surgical methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonsurgical innovations in the treatment of nonmelanoma skin cancer. Amini, S., Viera, MH., Valins, W., et al.[2021]

In a study of 40 patients with melanoma in-transit metastases treated with topical diphencyprone (DPCP), 25% achieved a complete response, and those with BRAF wild-type tumors were more likely to respond completely to treatment.

The presence of peritumoral CD8+ T-cells and PD-L1 expression may serve as potential biomarkers for predicting a better response to DPCP, suggesting that immune characteristics of the tumor could influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative and Spatial Analysis of CD8+/PD-1 Tumor-Infiltrating Lymphocytes as a Predictive Biomarker for Clinical Response of Melanoma In-Transit Metastases to Topical Immunotherapy. Haywood, S., Garioch, J., Ramaiya, A., et al.[2021]

In a study involving 50 patients with cutaneous metastatic melanoma, topical diphencyprone (DPCP) therapy resulted in complete clearance of skin disease in 46% of patients and a partial response in 38%.

DPCP is an inexpensive and well-tolerated treatment option, making it a viable choice for patients with skin metastases who cannot undergo or have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical immunotherapy with diphencyprone for in transit and cutaneously metastatic melanoma. Damian, DL., Saw, RP., Thompson, JF.[2022]

Topical diphencyprone (DPCP) treatment led to a significant regression of in-transit metastatic melanoma on the scalp, suggesting its potential as an effective immunomodulatory therapy.

Molecular analysis revealed that DPCP treatment resulted in a decrease in IL 17C/D/E/F expression and an increase in PLZF/CD27 and CTLA4 expression, indicating a shift in the TH17 lymphocyte subset that may contribute to the therapeutic effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TH17 is involved in the remarkable regression of metastatic malignant melanoma to topical diphencyprone. Martiniuk, F., Damian, DL., Thompson, JF., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3412255/

Topical Diphencyprone as an Effective Treatment for ... DPCP was reported as an effective treatment for the local cutaneous metastatic melanoma on its own, and in combination with cimetidine or dacarbazine and ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S266702672200087X

Modulation of Inflammatory Proteins in Serum May Reflect ... Diphencyprone (DPCP), a topical contact sensitizer, has shown efficacy in treating cutaneous melanoma metastases, including at times beyond the directly ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.e21071

Topical immunotherapy with diphencyprone (DPCP) for in- ... 6 (40%) had stable disease. 6 patients stopped DPCP: 3 from systemic progression and 3 from toxicity. 1 had CTACE 3/4 skin ulceration but ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01711684

NCT01711684 | Treatment of Cutaneous Metastases With ... In this study, the investigators will use DPCP to treat cutaneous metastases of various cancers including melanoma. Our overall intention is to get a better ...

5. jaad.org jaad.org/article/S0190-9622(20)30563-6/fulltext

Response rates of cutaneous melanoma metastases to ... This meta-analysis shows satisfactory response rates, which makes us believe that larger studies should be considered to evaluate how DPCP might ...

6. cdn.caymanchem.com cdn.caymanchem.com/cdn/msds/27982m.pdf

Safety Data Sheet Skin irritation 2. H315 Causes skin irritation. Sensitization - skin 1 H317 May cause an allergic skin reaction. · Label elements. · GHS label ...

7. dermnetnz.org dermnetnz.org/topics/diphenylcyclopropenone

Diphenylcyclopropenone, diphencyprone There are safety concerns about diphenylcyclopropenone. Although diphenylcyclopropenone is non-mutagenic in the Ames test, its precursor and possible ...

8. jaad.org jaad.org/article/S0190-9622(24)01379-3/fulltext

51687 Safety, Tolerability, and Efficacy of Diphencyprone ... A ten-week trial of DPCP for CNs demonstrated safety, tolerability, and subjective efficacy in six of 12 participants.

9. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/1359490

The Safety and Efficacy of Diphencyprone for ... Topical diphencyprone (DPCP) immunotherapy is used to treat refractory and advanced alopecia areata. Although not approved for this indication by the US.