Dose Escalation Trial to Evaluate Dose Limiting Toxicity/Maximum Tolerated Dose of Microneedle Arrays Containing Doxorubicin (D-MNA) in Basal Cell Carcinoma (BCC)

Study Overview
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Brief Summary
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This is a Phase I study in participants with superficial or nodular Basal Cell Carcinoma (BCC), designed to assess dose limiting toxicities and maximum tolerated dose, efficacy, safety, and tolerability of dissolvable, tip-loaded, microneedle arrays containing doxorubicin (D-MNA).

Detailed Description
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This is a Phase I study in participants with superficial or nodular Basal Cell Carcinoma (BCC), designed to assess dose limiting toxicities and maximum tolerated dose, efficacy, safety, and tolerability of dissolvable, tip-loaded, microneedle arrays containing doxorubicin (D-MNA). Doxorubicin is a cytotoxic anthracycline antibiotic and is currently approved for the treatment of a broad range of cancers, including but not limited to: breast, bladder, gastric, and ovarian cancers; small cell lung cancer; acute lymphoblastic leukemia; and acute myelo blastic leukemia. SkinJect, Inc. has developed a novel delivery system in the form of a tip-loaded dissolvable microneedle array (MNA) which will allow for topical delivery of doxorubicin directly to the lesion at concentrations that are far below standard systemic dosing, thereby reducing the adverse events associated with systemic delivery. The primary objective of this investigation is to establish the highest safe and tolerable dose of single applications of D-MNA, one application per week for three weeks in placebo, 25 µg, 50 µg, 100 µg, and 200 µg dose groups in participants with BCC.

Official Title
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An Open-Label Dose Escalation Trial to Evaluate Dose Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD), Safety, and Tolerability of Microneedle Arrays Containing Doxorubicin (D-MNA) in Participants With Basal Cell Carcinoma (BCC)

Conditions
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Basal Cell Carcinoma

Intervention / Treatment
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* Drug: Placebo-containing MNA
* Drug: 25 µg doxorubicin-containing MNA
* Drug: 50 µg doxorubicin-containing MNA
* Drug: 100 µg doxorubicin-containing MNA
* Drug: 200 µg doxorubicin-containing MNA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males and females, 40+ years in general good health as assessed by the investigator. BCC (subtype: superficial or nodular) confirmed histologically by diagnostic shave biopsy at the Screening Visit Primary BCC (i.e., no previous treatment) Lesion size ≥ 4 mm2 or 2 x 2 mm and ≤ 169 mm2 or 13 x 13 mm Participant must have no other clinically significant abnormal findings in his/her medical history, physical examination or clinical laboratory test results as assessed by the investigator Negative urine pregnancy at study entry for female of child bearing potential Men and women of child-producing potential must agree to use adequate contraception according to standard instructions by the investigator until the completion of the study Participant must to be willing to adhere to the instructions of the investigator and his or her research team Participant must sign an Informed Consent Form prior to any study specific procedures and entry into the study Exclusion Criteria: Evidence of clinically significant, unstable medical conditions as assessed by the investigator Excisional biopsy performed on the lesion to be treated in this study Recent therapy(ies) to the BCC treatment area Recurrent BCC (previously treated) at the site presented for treatment BCC lesion to be treated is located in an area where excisional biopsy is undesired or aesthetically unacceptable to the participant Previously demonstrated sensitivity to doxorubicin or carboxymethyl cellulose. Participant with other active malignancies with the exception of non-metastatic prostate cancer and carcinoma in situ of the skin and cervix Concomitant disease requiring systemic immunosuppressive treatment Genetic skin cancer disorder, e.g., basal cell nevus syndrome Participant is pregnant or breastfeeding Treatment with another investigational drug, device, or other intervention within 3 months prior to the Screening Visit Existing condition or treatment within 3 months prior to the Screening Visit that may have impact on clinical outcome for the treatment of BCC or delay in wound healing from the elliptical excision

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 3+3 Design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo-containing MNA<br>Placebo | Drug: Placebo-containing MNA<br>* A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering a placebo.<br>* Other names: Placebo;|
| Experimental: 25 µg Doxorubicin-containing MNA<br>D-MNA's containing 25 µg of doxorubicin hydrochloride | Drug: 25 µg doxorubicin-containing MNA<br>* A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 25 µg of doxorubicin hydrochloride.<br>* Other names: 25 µg D-MNA;|
| Experimental: 50 µg Doxorubicin-containing MNA<br>D-MNA's containing 50 µg of doxorubicin hydrochloride | Drug: 50 µg doxorubicin-containing MNA<br>* A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 50 µg of doxorubicin hydrochloride.<br>* Other names: 50 µg D-MNA;|
| Experimental: 100 µg Doxorubicin-containing MNA<br>D-MNA's containing 100 µg of doxorubicin hydrochloride | Drug: 100 µg doxorubicin-containing MNA<br>* A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 100 µg of doxorubicin hydrochloride.<br>* Other names: 100 µg D-MNA;|
| Experimental: 200 µg Doxorubicin-containing MNA<br>D-MNA's containing 200 µg of doxorubicin hydrochloride | Drug: 200 µg doxorubicin-containing MNA<br>* A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 200 µg of doxorubicin hydrochloride.<br>* Other names: 200 µg D-MNA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities as Assessed by Local Skin Response (LSR) Grading Scale | Dose Limiting Toxicity (DLT) in Trial Subjects Assessed by Local Skin Response Grading Scale, 0-4, 4 being the worst dermal response | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Eradicated Basal Cell Carcinoma as Measured by Histological Analysis | Histological confirmation by central reading by pathologist of basal cell carcinoma eradication in trial participants | 4 weeks |