D-MNA for Basal Cell Carcinoma

Recruiting at 5 trial locations

Overseen By Marietta P Radona, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: SkinJect, Inc.

Must not be taking: Systemic chemotherapy, Topical immunomodulators

Disqualifiers: Pregnancy, Immunocompromised, Active malignancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of the study is to learn about the safety and how effective two different strengths of D-MNA compared to a placebo (a look-alike substance that contains no drug) in the treatment of nodular basal cell skin cancer

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used systemic chemotherapeutic agents in the past 12 months or certain topical agents near the target lesion in the past 4 weeks.

What data supports the effectiveness of the drug D-MNA for treating Basal Cell Carcinoma?

Research on doxorubicin, a component of D-MNA, shows that it can be effectively delivered to the skin using nanoparticles, which may enhance its ability to treat skin cancer while reducing side effects. ^{1 2 3 4 5}

How is the drug D-MNA different from other treatments for basal cell carcinoma?

D-MNA (Doxorubicin Micro-Array) is unique because it uses a modified form of doxorubicin that can form strong DNA cross-links without needing metabolic activation, potentially reducing drug resistance and side effects like cardiotoxicity. This makes it a potent option for targeting cancer cells more effectively than traditional doxorubicin. ^{6 7 8 9 10}

Eligibility Criteria

This study is for adults with nodular basal cell carcinoma, a common type of skin cancer. Participants must meet certain health criteria to join, but specific inclusion and exclusion details are not provided here.

Inclusion Criteria

I am at least 18 years old and not pregnant.

I am willing to avoid excessive sunlight and not use tanning beds.

I am willing and able to follow the study's treatment plan and attend all follow-up visits.

Exclusion Criteria

Pregnant, lactating, or planning to become pregnant

I have used creams or ointments to boost immunity near my lesion recently.

My basal cell carcinoma is in a specific area or was treated with radiation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive D-MNA or placebo intradermal patch once weekly for 2 weeks

2 weeks

2 visits (in-person)

Excision

The target lesion is excised after two weeks of treatment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• D-MNA

Trial Overview The trial is testing the safety and effectiveness of two doses (100 mcg and 200 mcg) of a drug called D-MNA against a placebo in treating nodular basal cell carcinoma.

Participant Groups

Group I: Arm B Active Control 1 Intervention

D-MNA 100 mcg intradermal patch, given once weekly for 2 weeks

Group II: Arm A Active Control 1 Intervention

D-MNA 200 mcg, intradermal patch, given once weekly for 2 weeks.

Group III: Arm C Placebo Group 1 Intervention

P-MNA, intradermal patch, given once weekly for 2 weeks

Who Is Running the Clinical Trial?

SkinJect, Inc.

Lead Sponsor

Trials

3

Recruited

100+

Findings from Research

Doxorubicin and daunorubicin bind to melanin, significantly increasing their IC50 values, which indicates that melanin can reduce the effectiveness of these chemotherapeutic agents in treating cancer cells, as shown in MOLT-4 cells.

Cisplatin does not bind to melanin, meaning its effectiveness is not affected by melanin, and the study suggests that melanin binding could lead to unwanted drug accumulation in the skin and potential chemoprotective effects against chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melanin inhibits cytotoxic effects of doxorubicin and daunorubicin in MOLT 4 cells. Svensson, SP., Lindgren, S., Powell, W., et al.[2019]

In a review of 204 cases of Merkel cell carcinoma (MCC) treated with chemotherapy, the most common regimens showed a high overall response rate of 75.7% for cyclophosphamide/doxorubicin/vincristine and 60% for etoposide/cisplatin, indicating that chemotherapy can be effective for this aggressive skin cancer.

Despite the effectiveness of chemotherapy, there were some safety concerns, with a 3.4% rate of toxic deaths among patients, suggesting that while chemoradiation can be a viable option for advanced MCC, careful patient selection is crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in neuroendocrine/Merkel cell carcinoma of the skin: case series and review of 204 cases. Tai, PT., Yu, E., Winquist, E., et al.[2022]

Smaller STEALTH liposomes (82, 101, and 154 nm) showed significantly higher accumulation in tumor and skin tissues compared to larger liposomes (241 nm), but no preferential accumulation in tumors over skin or paws was achieved based solely on size.

Liposomes of 100 and 157 nm effectively delayed tumor growth in a murine model, demonstrating similar efficacy and outperforming the larger 255 nm liposomes, suggesting that smaller liposome sizes may enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of biodistribution of STEALTH liposomes to tumor and skin: influence of liposome diameter and implications for toxicity and therapeutic activity. Charrois, GJ., Allen, TM.[2019]

Doxorubicin (Dox) delivered through solid lipid nanoparticles (SLNs) showed a mean particle size of 92 nm and an impressive encapsulation efficiency of 86%, indicating effective formulation for topical delivery.

In both in vitro and in vivo studies, Dox-loaded SLNs demonstrated superior cytotoxic effects against melanoma cells compared to traditional Dox solutions, suggesting a promising method for targeting skin cancer while potentially reducing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermal delivery of doxorubicin-loaded solid lipid nanoparticles for the treatment of skin cancer. Tupal, A., Sabzichi, M., Ramezani, F., et al.[2017]

In a study of 10 patients with Merkel cell carcinoma (MCC), routine H&E staining missed micrometastatic cancer in 22% of sentinel lymph node biopsies, highlighting the need for more sensitive detection methods.

Immunostaining with the anti-CK-20 antibody proved to be the most effective method for identifying micrometastatic MCC, demonstrating both high sensitivity and specificity compared to standard H&E staining.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunostaining for cytokeratin 20 improves detection of micrometastatic Merkel cell carcinoma in sentinel lymph nodes. Su, LD., Lowe, L., Bradford, CR., et al.[2019]

The anthracycline analogue MRA-CN is 1400 times more effective at killing human leukemia cells than doxorubicin (DOX), primarily due to its ability to inhibit DNA and RNA synthesis and produce DNA interstrand cross-links.

MRA-CN causes significant DNA fragmentation and nucleolar macrosegregation, effects that are linked to its unique chemical structure, particularly the alpha-CN substituent on the morpholinyl group, which enhances its antitumor potency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin and doxorubicin on the survival, DNA integrity, and nucleolar morphology of human leukemia cells in vitro. Wassermann, K., Zwelling, LA., Mullins, TD., et al.[2013]

MRA-CN, a cyanomorpholino derivative of doxorubicin, effectively produces DNA cross-links in both multidrug-resistant and sensitive cancer cells, indicating its potential as a powerful treatment option for resistant cancers.

The drug's unique properties, such as its lipophilicity and reduced affinity for the P-glycoprotein efflux pump, contribute to its non-cross-resistance in multidrug-resistant cells, allowing it to enter the nucleus and exert its effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DNA cross-linking and cytotoxicity of the alkylating cyanomorpholino derivative of doxorubicin in multidrug-resistant cells. Scudder, SA., Brown, JM., Sikic, BI.[2019]

Cyanomorpholino doxorubicin (MRA-CN) binds covalently to DNA in human ovarian carcinoma cells, with 85% of the drug bound regardless of concentration, indicating its strong potential for effective cancer treatment without the need for metabolic activation.

In contrast, morpholino doxorubicin (MRA) requires metabolic activation to bind to DNA, showing significantly less binding (only 10% at 10 nM) without the presence of liver microsomes and NADPH, highlighting MRA-CN's advantage in avoiding drug resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of covalent DNA binding of morpholino and cyanomorpholino derivatives of doxorubicin. Lau, DH., Durán, GE., Sikic, BI.[2019]

Cyanomorpholinyl adriamycin (CMA) is a highly potent antineoplastic drug that shows significant antitumor activity at low doses (≤0.05 mg/kg) without causing neurotoxicity, unlike higher doses (≥0.1 mg/kg) which lead to neurotoxic symptoms in mice.

CMA exhibits a different cellular distribution compared to adriamycin (ADR), with increased dermatotoxicity and antineoplastic effects, suggesting it may be a more effective treatment option with careful dose management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurotoxicity and dermatotoxicity of cyanomorpholinyl adriamycin. Cramer, SC., Rhodes, RH., Acton, EM., et al.[2019]

Doxorubicin, at cytostatic concentrations, can induce morphological changes and increase melanin content in B16 melanoma cells, similar to theophylline, while also causing a cell cycle arrest in the G2 + M phase.

Unlike retinoic acid, which did not affect melanin content, doxorubicin and MSH both enhanced melanin production and tyrosinase activity, indicating that doxorubicin can effectively promote differentiation in melanoma cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative studies on the effects of doxorubicin and differentiation inducing agents on B16 melanoma cells. Supino, R., Mariani, M., Colombo, A., et al.[2019]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

Melanin inhibits cytotoxic effects of doxorubicin and daunorubicin in MOLT 4 cells. [2019]

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

Chemotherapy in neuroendocrine/Merkel cell carcinoma of the skin: case series and review of 204 cases. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Rate of biodistribution of STEALTH liposomes to tumor and skin: influence of liposome diameter and implications for toxicity and therapeutic activity. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Dermal delivery of doxorubicin-loaded solid lipid nanoparticles for the treatment of skin cancer. [2017]

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

Immunostaining for cytokeratin 20 improves detection of micrometastatic Merkel cell carcinoma in sentinel lymph nodes. [2019]

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

Effects of 3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin and doxorubicin on the survival, DNA integrity, and nucleolar morphology of human leukemia cells in vitro. [2013]

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

DNA cross-linking and cytotoxicity of the alkylating cyanomorpholino derivative of doxorubicin in multidrug-resistant cells. [2019]

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

Characterization of covalent DNA binding of morpholino and cyanomorpholino derivatives of doxorubicin. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Neurotoxicity and dermatotoxicity of cyanomorpholinyl adriamycin. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Comparative studies on the effects of doxorubicin and differentiation inducing agents on B16 melanoma cells. [2019]