Diphencyprone + Immunotherapy for Skin Cancer

Overseen by Philip Friedlander, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Trial Summary

What is the purpose of this trial?

This trial tests a skin-applied cream called DPCP on patients with skin tumors. The cream aims to boost the immune system's ability to fight cancer, used together with other drugs that help the immune system recognize cancer cells. DPCP is often used in topical immunotherapy for conditions like alopecia areata, where it helps induce an immune response.

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.

What data supports the effectiveness of the treatment Diphencyprone (DPCP) for skin cancer?

Research shows that Diphencyprone (DPCP), used as a topical treatment for melanoma skin cancer, has led to complete clearance of skin lesions in 46% of patients and partial improvement in 38% of patients. This suggests that DPCP can be an effective option for treating certain types of skin cancer, especially when other treatments are not suitable. ^{1 2 3 4 5}

Is Diphencyprone + Immunotherapy generally safe for humans?

Immune checkpoint inhibitors, a type of immunotherapy, can cause skin-related side effects, which are common but usually mild to moderate. Some rare and severe skin reactions, like bullous pemphigoid, have been reported, but they can often be managed with medication without stopping treatment. ^{6 7 8 9 10}

How is the Diphencyprone + Immunotherapy treatment for skin cancer different from other treatments?

This treatment combines Diphencyprone (DPCP), a topical agent that stimulates the immune system, with immune checkpoint inhibitors, which are drugs that help the immune system recognize and attack cancer cells. This combination is unique because it uses both a topical and systemic approach to enhance the body's immune response against skin cancer. ^{6 8 11 12 13}

Research Team

Nicholas Gulati, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Philip Friedlander, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Diphencyprone (DPCP) (Immunomodulator)
• Immune Checkpoint Inhibition (PD-1 or PD-L1 Inhibitor)

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Topical immunotherapy with diphencyprone (DPCP) for in-transit and unresectable cutaneous melanoma lesions: an inaugural Canadian series. [2022]

2. United States 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. [2021]

3. Spain pubmed.ncbi.nlm.nih.gov

Diphencyprone as a therapeutic option in cutaneous metastasis of melanoma. A single-institution experience. [2023]

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

Topical immunotherapy with diphencyprone for in transit and cutaneously metastatic melanoma. [2022]

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

TH17 is involved in the remarkable regression of metastatic malignant melanoma to topical diphencyprone. [2021]

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

Successful Outpatient Management of Diffuse Photosensitive Bullous Dermatitis Following Pembrolizumab Therapy. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

Late presentation of generalised bullous pemphigoid-like reaction in a patient treated with pembrolizumab for metastatic melanoma. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

A Retrospective, Single-Institution Experience of Bullous Pemphigoid as an Adverse Effect of Immune Checkpoint Inhibitors. [2022]

9. France pubmed.ncbi.nlm.nih.gov

[Dermatologic toxicities of immune checkpoint inhibitors]. [2018]

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

Nonsurgical innovations in the treatment of nonmelanoma skin cancer. [2021]

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

Lichenoid dermatitis in three patients with metastatic melanoma treated with anti-PD-1 therapy. [2022]

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

Bullous Pemphigoid Associated With a New Combination Checkpoint Inhibitor Immunotherapy [2022]

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

Steroid-Refractory Lichenoid Eruption Associated with Pembrolizumab in a Patient with Non-Small Cell Lung Cancer. [2023]