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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called D-MNA (Doxorubicin Micro-Array) for nodular basal cell carcinoma, a common type of skin cancer. The study aims to determine the safety and effectiveness of two different doses of D-MNA compared to a placebo (a harmless look-alike patch). Participants will receive either the D-MNA patch or a placebo patch once a week for two weeks. Individuals with a confirmed diagnosis of untreated nodular basal cell carcinoma, not located on the face or other excluded areas, might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to the development of a potentially effective new treatment.

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.

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

Research shows that D-MNA, a new treatment being tested for basal cell carcinoma, is generally safe. Earlier studies found D-MNA to be safe and showed early signs of effectiveness against skin cancer. Participants in one study tolerated D-MNA well at various doses, with no serious side effects reported. Even at higher doses, D-MNA did not cause major harmful effects. These results suggest that D-MNA is well-tolerated and could be a safe option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because D-MNA introduces a unique approach to treating basal cell carcinoma with an innovative delivery method. Unlike traditional treatments that typically involve surgical removal or topical therapies, D-MNA uses an intradermal patch, which is less invasive and potentially more convenient for patients. The treatment features a microneedle array that delivers the active ingredient directly into the skin, which could enhance the precision and effectiveness of the medication. Additionally, the treatment is administered in just two weekly sessions, offering a quicker regimen compared to many existing options.

What evidence suggests that D-MNA might be an effective treatment for basal cell carcinoma?

Research has shown that D-MNA is a promising treatment for basal cell carcinoma, a common type of skin cancer. In earlier studies, over 60% of patients experienced complete disappearance of their cancer, meaning it was no longer detectable. Importantly, these studies found no serious side effects, indicating the treatment was safe at the doses tested. In this trial, participants will receive either a 100 mcg or 200 mcg dose of D-MNA via a microneedle patch, or a placebo patch. D-MNA uses a microneedle patch to deliver the drug doxorubicin directly to the cancer site, enhancing penetration compared to creams. This targeted delivery might explain its superior performance over some other treatments. Overall, these findings suggest that D-MNA could be an effective and safe option for treating basal cell carcinoma. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1.

onclive.com

onclive.com/view/d-mna-displays-potential-as-noninvasive-therapy-in-basal-cell-carcinoma-of-the-skin

D-MNA Displays Potential as Noninvasive Therapy in ...

D-MNA treatment for BCC showed no dose-limiting toxicities or serious adverse effects, with over 60% achieving complete clinical clearance. The ...

2.

cancernetwork.com

cancernetwork.com/view/fda-accepts-type-c-meeting-for-doxorubicin-mna-in-basal-cell-carcinoma-of-the-skin

FDA Accepts Type C Meeting for Doxorubicin-MNA in ...

D-MNA achieved complete clinical clearance in 60% of patients, with no dose-limiting toxicities or serious adverse effects observed in those ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03646188?cond=basal%2520cell%2520carcinoma%26term=Doxorubicin%26rank=1

Study Details | NCT03646188 | Dose Escalation Trial to ...

This is a Phase I study in participants with superficial or nodular Basal Cell Carcinoma (BCC), designed to assess dose limiting toxicities and maximum ...

4.

medicuspharma.com

medicuspharma.com/medicus-pharma-ltd-provides-update-on-doxorubicin-containing-novel-microneedle-array-d-mna-clinical-development-program-for-the-treatment-of-basal-cell-carcinoma-bcc-of-the-skin-and-reports-secon/

Medicus Pharma

The study also describes the efficacy of the investigational product, D-MNA, with six (6) participants experiencing complete responses. The ...

5.

drug-dev.com

drug-dev.com/transdermal-delivery-skinjects-doxorubicin-loaded-dissolvable-microneedle-array-d-mna-a-revolutionary-approach-to-transdermal-drug-delivery/

SkinJect's Doxorubicin-Loaded Dissolvable Microneedle ...

D-MNA allows for precise delivery of doxorubicin to Basal Cell Carcinoma sites, improving efficacy compared to topical creams that may not penetrate deeply ...

6.

medicuspharma.com

medicuspharma.com/medicus-pharma-ltd-publishes-phase-1-clinical-study-report-demonstrating-safety-tolerability-in-all-participants-with-basal-cell-carcinoma/

Medicus Pharma Ltd. Publishes Phase 1 Clinical Study ...

The investigational product, D-MNA was found to be safe and well-tolerated across all dose levels in all thirteen (13) participants enrolled in the study.

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06608238

NCT06608238 | The Purpose of This Study is to Evaluate ...

A double-blind, randomized, placebo-controlled study designed to evaluate the safety and efficacy of D-MNA which is administered as an intradermal injection.