Microneedle Chemotherapy for Skin Cancer

(cSCC Trial)

Overseen By Charity L Ruhl, LPN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Falo, Louis, MD

Disqualifiers: Pregnancy, Cardiac disease, Autoimmune, others

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

Compensation: Varies

Number of Visits: 5

Duration: 3 weeks

48 Participants Needed

Trial Summary

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 be on any other investigational treatments. You also cannot receive other treatments for skin cancer, except for certain skin moisturizers without steroids or antibiotics.

What data supports the effectiveness of the drug Doxorubicin for treating skin cancer?

Research shows that Doxorubicin, a chemotherapy drug, has been effective in treating various types of cancer, including breast cancer and fibrosarcoma, by altering tissue distribution and improving the benefit-risk profile. Additionally, a similar drug, 4'-epi-doxorubicin, showed antitumor activity in cancers resistant to Doxorubicin, suggesting potential effectiveness in challenging cases. ^{1 2 3 4 5}

Is microneedle chemotherapy with doxorubicin safe for humans?

Liposomal formulations of doxorubicin, like Doxil and Myocet, are generally well tolerated and have been shown to reduce heart-related side effects compared to the free form of doxorubicin. However, they can still cause side effects like hand-foot syndrome (skin reaction on palms and soles), mouth sores, and low white blood cell counts. These formulations have been tested in various cancers, showing a different safety profile than traditional doxorubicin. ^{6 7 8 9 10}

How is the microneedle chemotherapy treatment for skin cancer different from other treatments?

The microneedle chemotherapy treatment for skin cancer is unique because it uses a microneedle array to deliver doxorubicin directly into the skin, potentially reducing side effects and improving drug delivery compared to traditional intravenous methods. ^{2 3 6 11 12}

What is the purpose of this trial?

The purpose of this study is to test a new method of experimental treatment for cutaneous squamous cell skin cancer, using small adhesive-like patches (a micro-needle applicator or MNA for short), which have dozens of very small micro-needles loaded with extremely low doses of doxorubicin, a chemotherapy agent. The overall goal of this study is to test the safety and effectiveness of these patches. The investigators have established the highest tolerated dose at 50 micrograms in a previous study for a different type of cancer that affects the skin. The investigators will thoroughly evaluate the skin where the patches are applied.

Research Team

Oleg E Akilov, MD, PhD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for adults with a confirmed diagnosis of cutaneous squamous cell skin cancer, which can be surgically removed and measures between 5mm to less than 100mm. Participants should have an ECOG status of 0-2, meaning they are fully active or at least capable of self-care, not on other experimental treatments, and able to follow study instructions. Pregnant individuals or those with significant heart issues, autoimmune diseases (with some exceptions), recent major surgery, lung conditions caused by drugs, or active infections like HIV/hepatitis cannot join.

Inclusion Criteria

Subjects must not be on any other investigational device/drug treatment

I can take care of myself and am up and about more than half of my waking hours.

Subjects must have specific pretreatment laboratory parameters

Exclusion Criteria

I have not had major surgery in the last 2 weeks.

Subjects who have sensitivity to drugs that provide local anesthesia

Subjects who are pregnant or lactating

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the MNA-D patch on 4 subsequent visits for a 20 minute time period at each application

3 weeks

4 visits (in-person)

Rest

A rest period following the initial treatment phase

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including final follow-up visit and excision of remaining cSCC lesion

3 weeks

1 visit (in-person)

Treatment Details

Interventions

• Doxorubicin
• Microneedle Array

Trial Overview The trial tests a new treatment using patches with tiny needles that deliver low doses of doxorubicin directly into the skin cancer area. The highest safe dose has been determined previously; now researchers want to see how effective this method is in treating skin cancer while monitoring safety closely.

Participant Groups

Group I: Microneedle Array Doxorubicin (MNA-D) Experimental Treatment 1 Intervention

Immunocompetent and immuno-incompetent subjects will receive the MNA-D patch on 4 subsequent visits for a 20 minute time period at each application and will include patients who have competent immune systems with cSCC meeting all other inclusion/exclusion criteria and patients considered immuno-incompetent post transplant with cSCC meeting all other inclusion/exclusion criteria.

Doxorubicin is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Adriamycin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in European Union as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in Canada as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in Japan as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Who Is Running the Clinical Trial?

Falo, Louis, MD

Lead Sponsor

Trials

2

Recruited

70+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a Phase I-II study involving 108 patients with advanced malignancies, 4'-epi-doxorubicin (epi-DX) showed a similar toxicity profile to doxorubicin (DX) but was better tolerated, with lower rates of vomiting, stomatitis, complete hair loss, and severe myelosuppression.

Epi-DX demonstrated antitumor activity across various cancers, including those resistant to DX, such as malignant melanoma and renal cancer, while also suggesting slightly reduced cardiac toxicity based on electrocardiographic assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic and therapeutic activity of 4'-epi-doxorubicin. Bonfante, V., Villani, F., Bonadonna, G.[2022]

The study found that the generic doxorubicin liposome injection developed by Sun Pharmaceuticals (SPIL) has a plasma and tissue distribution profile that is generally comparable to the reference product, Caelyx®, in murine models.

Minor differences in tissue distribution were noted, but these variations were likely due to biological differences rather than significant discrepancies between the two formulations, suggesting that SPIL's product may offer a similar benefit-risk profile as Caelyx®.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative plasma and tissue distribution of Sun Pharma's generic doxorubicin HCl liposome injection versus Caelyx® (doxorubicin HCl liposome injection) in syngeneic fibrosarcoma-bearing BALB/c mice and Sprague-Dawley rats. Burade, V., Bhowmick, S., Maiti, K., et al.[2018]

The proposed generic doxorubicin hydrochloride liposome injection (SPIL) demonstrated comparable antitumor efficacy to the reference product (Caelyx) in mouse models, significantly reducing tumor volume without significant differences in effectiveness at any tested dose.

Both SPIL and the reference injection exhibited similar toxicity profiles and pharmacokinetics, confirming their bioequivalence and supporting the development of affordable cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipodox® (generic doxorubicin hydrochloride liposome injection): in vivo efficacy and bioequivalence versus Caelyx® (doxorubicin hydrochloride liposome injection) in human mammary carcinoma (MX-1) xenograft and syngeneic fibrosarcoma (WEHI 164) mouse models. Burade, V., Bhowmick, S., Maiti, K., et al.[2018]

Among four newly synthesized anthracycline analogs, compound 4 demonstrated strong cytotoxic effects against various human tumor cell lines, comparable to or better than adriamycin (doxorubicin).

The other compounds (1, 2, and 3) showed moderate cytotoxicity across most cell lines, indicating that structural modifications can influence the efficacy of anthracycline derivatives in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibitory activity of four demethoxy fluorinated anthracycline analogs against five human-tumor cell lines. Horton, D., Khare, A.[2013]

The combination of Doxil (40 mg/m2) and vinorelbine (30 mg/m2) was found to be effective in treating metastatic breast cancer in a phase I study involving 30 women, with a recommended schedule for further testing.

This combination therapy demonstrated a favorable toxicity profile, with minimal severe side effects like neutropenia and a low incidence of significant nausea, vomiting, or hair loss, making it a promising option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of Doxil and vinorelbine in metastatic breast cancer. Burstein, HJ., Ramirez, MJ., Petros, WP., et al.[2020]

In a study comparing 40 patients treated with Lipodox® to 120 matched patients treated with Doxil®, Lipodox® showed a significantly lower overall response rate of 4.3% compared to 18% for Doxil®, indicating reduced efficacy in treating recurrent ovarian cancer.

Despite similar toxicity profiles between Lipodox® and Doxil®, the lack of equivalent efficacy suggests that further prospective clinical studies are needed before Lipodox® can be considered a suitable substitute for Doxil®.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is it equivalent? Evaluation of the clinical activity of single agent Lipodox® compared to single agent Doxil® in ovarian cancer treatment. Smith, JA., Costales, AB., Jaffari, M., et al.[2019]

Liposomal formulations of doxorubicin, such as Doxil and Myocet, reduce the risk of heart-related toxicities associated with the free form of doxorubicin by sequestering the drug away from the heart and targeting it more towards tumors and other organs like the liver and spleen.

While liposomal doxorubicin allows for a greater cumulative dose to be safely administered, it comes with its own toxicities, such as palmar-plantar erythrodysaesthesia with Doxil, highlighting the need for careful consideration in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of liposomal formulations of doxorubicin with drug administered in free form: changing toxicity profiles. Waterhouse, DN., Tardi, PG., Mayer, LD., et al.[2018]

Stealth liposomal doxorubicin (Caelyx, Doxil) shows promise as a treatment for breast cancer, leveraging its unique liposomal formulation to improve drug delivery and efficacy.

The liposomal encapsulation of doxorubicin significantly alters its pharmacokinetics and reduces toxicity compared to traditional non-liposomal doxorubicin, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caelyx (stealth liposomal doxorubicin) in the treatment of advanced breast cancer. Ranson, MR., Cheeseman, S., White, S., et al.[2019]

Pegylated liposomal doxorubicin is generally well tolerated in patients with solid tumors, with lower rates of severe side effects like alopecia and cardiotoxicity compared to traditional doxorubicin, as shown in a phase II trial for refractory ovarian cancer.

While it reduces some adverse effects, pegylated liposomal doxorubicin may increase the risk of mucositis, and ongoing studies are exploring optimal dosing and safety when combined with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety aspects of pegylated liposomal doxorubicin in patients with cancer. Alberts, DS., Garcia, DJ.[2018]

Myocet®, a non-pegylated liposome-encapsulated form of doxorubicin, is designed to enhance the effectiveness of doxorubicin while reducing its cardiotoxicity, making it a safer option for breast cancer and other tumors.

Clinical evidence indicates that Myocet® has a lower incidence of hematological toxicity compared to conventional doxorubicin, and it effectively reduces the severity of cardiac events associated with treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Non-pegylated doxorubicin (Myocet®) as the less cardiotoxic alternative of free doxorubicin]. Nagykálnai, T.[2018]

Doxorubicin, a powerful anticancer drug, can cause severe local tissue damage when it leaks out of veins during administration, as seen in a case study of a 70-year-old woman who developed an indolent ulcer on her hand and wrist.

After initial nonoperative care and a failed skin graft, the use of porcine grafts helped stimulate healing, allowing for a successful split-thickness skin graft later, highlighting a potential treatment strategy for managing drug extravasation injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venous extravasation of doxorubicin HCl with secondary skin ulceration. Barden, GA.[2019]

Doxorubicin incorporated into solid lipid nanospheres (SLN) resulted in significantly higher drug concentrations in the blood and certain tissues (lung, spleen, brain) compared to the commercial doxorubicin solution, indicating improved bioavailability.

The SLN formulation also demonstrated a different distribution profile, with lower concentrations of doxorubicin found in the liver, heart, and kidney, which may suggest a safer profile by potentially reducing toxicity to these organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of doxorubicin incorporated in solid lipid nanospheres (SLN). Zara, GP., Cavalli, R., Fundarò, A., et al.[2015]

References

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

Toxic and therapeutic activity of 4'-epi-doxorubicin. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Comparative plasma and tissue distribution of Sun Pharma's generic doxorubicin HCl liposome injection versus Caelyx® (doxorubicin HCl liposome injection) in syngeneic fibrosarcoma-bearing BALB/c mice and Sprague-Dawley rats. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Lipodox® (generic doxorubicin hydrochloride liposome injection): in vivo efficacy and bioequivalence versus Caelyx® (doxorubicin hydrochloride liposome injection) in human mammary carcinoma (MX-1) xenograft and syngeneic fibrosarcoma (WEHI 164) mouse models. [2018]

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

Inhibitory activity of four demethoxy fluorinated anthracycline analogs against five human-tumor cell lines. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Phase I study of Doxil and vinorelbine in metastatic breast cancer. [2020]

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

Is it equivalent? Evaluation of the clinical activity of single agent Lipodox® compared to single agent Doxil® in ovarian cancer treatment. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

A comparison of liposomal formulations of doxorubicin with drug administered in free form: changing toxicity profiles. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Caelyx (stealth liposomal doxorubicin) in the treatment of advanced breast cancer. [2019]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Safety aspects of pegylated liposomal doxorubicin in patients with cancer. [2018]

10. Hungary pubmed.ncbi.nlm.nih.gov

[Non-pegylated doxorubicin (Myocet®) as the less cardiotoxic alternative of free doxorubicin]. [2018]

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

Venous extravasation of doxorubicin HCl with secondary skin ulceration. [2019]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of doxorubicin incorporated in solid lipid nanospheres (SLN). [2015]