Dose Escalation Trial to Evaluate Dose Limiting Toxicity/Maximum Tolerated Dose of Microneedle Arrays Containing Doxorubicin (D-MNA) in Basal Cell Carcinoma (BCC)
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo-containing MNA Placebo |
Drug: Placebo-containing MNA
A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering a placebo.
Other Names:
|
| Experimental: 25 µg Doxorubicin-containing MNA D-MNA's containing 25 µg of doxorubicin hydrochloride |
Drug: 25 µg doxorubicin-containing MNA
A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 25 µg of doxorubicin hydrochloride.
Other Names:
|
| Experimental: 50 µg Doxorubicin-containing MNA D-MNA's containing 50 µg of doxorubicin hydrochloride |
Drug: 50 µg doxorubicin-containing MNA
A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 50 µg of doxorubicin hydrochloride.
Other Names:
|
| Experimental: 100 µg Doxorubicin-containing MNA D-MNA's containing 100 µg of doxorubicin hydrochloride |
Drug: 100 µg doxorubicin-containing MNA
A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 100 µg of doxorubicin hydrochloride.
Other Names:
|
| Experimental: 200 µg Doxorubicin-containing MNA D-MNA's containing 200 µg of doxorubicin hydrochloride |
Drug: 200 µg doxorubicin-containing MNA
A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 200 µg of doxorubicin hydrochloride.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose Limiting Toxicities as Assessed by Local Skin Response (LSR) Grading Scale [4 weeks]
Dose Limiting Toxicity (DLT) in Trial Subjects Assessed by Local Skin Response Grading Scale, 0-4, 4 being the worst dermal response
Secondary Outcome Measures
- Number of Participants With Eradicated Basal Cell Carcinoma as Measured by Histological Analysis [4 weeks]
Histological confirmation by central reading by pathologist of basal cell carcinoma eradication in trial participants
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Center for Clinical and Cosmetic Research | Aventura | Florida | United States | 33180 |
Sponsors and Collaborators
- SkinJect, Inc.
Investigators
- Study Director: Gregory Suplick, InClinica, Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.- SKNJCT-001
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo-containing MNA | 25 µg Doxorubicin-containing MNA | 50 µg Doxorubicin-containing MNA | 100 µg Doxorubicin-containing MNA | 200 µg Doxorubicin-containing MNA |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo Placebo-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering a placebo. | D-MNA's containing 25 µg of doxorubicin hydrochloride 25 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 25 µg of doxorubicin hydrochloride. | D-MNA's containing 50 µg of doxorubicin hydrochloride 50 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 50 µg of doxorubicin hydrochloride. | D-MNA's containing 100 µg of doxorubicin hydrochloride 100 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 100 µg of doxorubicin hydrochloride. | D-MNA's containing 200 µg of doxorubicin hydrochloride 200 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 200 µg of doxorubicin hydrochloride. |
| Period Title: Overall Study | |||||
| STARTED | 3 | 3 | 3 | 3 | 1 |
| COMPLETED | 3 | 3 | 3 | 3 | 1 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Placebo-containing MNA | 25 µg Doxorubicin-containing MNA | 50 µg Doxorubicin-containing MNA | 100 µg Doxorubicin-containing MNA | 200 µg Doxorubicin-containing MNA | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo Placebo-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering a placebo. | D-MNA's containing 25 µg of doxorubicin hydrochloride 25 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 25 µg of doxorubicin hydrochloride. | D-MNA's containing 50 µg of doxorubicin hydrochloride 50 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 50 µg of doxorubicin hydrochloride. | D-MNA's containing 100 µg of doxorubicin hydrochloride 100 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 100 µg of doxorubicin hydrochloride. | D-MNA's containing 200 µg of doxorubicin hydrochloride 200 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 200 µg of doxorubicin hydrochloride. | Total of all reporting groups |
| Overall Participants | 3 | 3 | 3 | 3 | 1 | 13 |
| Age (Count of Participants) | ||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
1
33.3%
|
2
66.7%
|
2
66.7%
|
0
0%
|
0
0%
|
5
38.5%
|
| >=65 years |
2
66.7%
|
1
33.3%
|
1
33.3%
|
3
100%
|
1
100%
|
8
61.5%
|
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
64.67
(31.72)
|
61.33
(8.505)
|
63.33
(12.34)
|
79
(6.08)
|
67
(NA)
|
67.35
(14.48)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
0
0%
|
1
33.3%
|
2
66.7%
|
1
33.3%
|
0
0%
|
4
30.8%
|
| Male |
3
100%
|
2
66.7%
|
1
33.3%
|
2
66.7%
|
1
100%
|
9
69.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
1
7.7%
|
| Not Hispanic or Latino |
3
100%
|
3
100%
|
2
66.7%
|
3
100%
|
1
100%
|
12
92.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
3
100%
|
3
100%
|
3
100%
|
3
100%
|
1
100%
|
13
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | ||||||
| United States |
3
100%
|
3
100%
|
3
100%
|
3
100%
|
1
100%
|
13
100%
|
Outcome Measures
| Title | Number of Participants With Dose Limiting Toxicities as Assessed by Local Skin Response (LSR) Grading Scale |
|---|---|
| Description | Dose Limiting Toxicity (DLT) in Trial Subjects Assessed by Local Skin Response Grading Scale, 0-4, 4 being the worst dermal response |
| Time Frame | 4 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All evaluable subjects |
| Arm/Group Title | Placebo-containing MNA | 25 µg Doxorubicin-containing MNA | 50 µg Doxorubicin-containing MNA | 100 µg Doxorubicin-containing MNA | 200 µg Doxorubicin-containing MNA |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo Placebo-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering a placebo. | D-MNA's containing 25 µg of doxorubicin hydrochloride 25 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 25 µg of doxorubicin hydrochloride. | D-MNA's containing 50 µg of doxorubicin hydrochloride 50 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 50 µg of doxorubicin hydrochloride. | D-MNA's containing 100 µg of doxorubicin hydrochloride 100 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 100 µg of doxorubicin hydrochloride. | D-MNA's containing 200 µg of doxorubicin hydrochloride 200 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 200 µg of doxorubicin hydrochloride. |
| Measure Participants | 3 | 3 | 3 | 3 | 1 |
| Number [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Eradicated Basal Cell Carcinoma as Measured by Histological Analysis |
|---|---|
| Description | Histological confirmation by central reading by pathologist of basal cell carcinoma eradication in trial participants |
| Time Frame | 4 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All evaluable subjects |
| Arm/Group Title | Placebo-containing MNA | 25 µg Doxorubicin-containing MNA | 50 µg Doxorubicin-containing MNA | 100 µg Doxorubicin-containing MNA | 200 µg Doxorubicin-containing MNA |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo Placebo-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering a placebo. | D-MNA's containing 25 µg of doxorubicin hydrochloride 25 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 25 µg of doxorubicin hydrochloride. | D-MNA's containing 50 µg of doxorubicin hydrochloride 50 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 50 µg of doxorubicin hydrochloride. | D-MNA's containing 100 µg of doxorubicin hydrochloride 100 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 100 µg of doxorubicin hydrochloride. | D-MNA's containing 200 µg of doxorubicin hydrochloride 200 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 200 µg of doxorubicin hydrochloride. |
| Measure Participants | 3 | 3 | 3 | 3 | 1 |
| Number [Participants] |
1
33.3%
|
2
66.7%
|
1
33.3%
|
1
33.3%
|
1
100%
|
Adverse Events
| Time Frame | 50 days | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events were recorded throughout the study and at early discontinuation. AEs and medical conditions were coded using the Medical Dictionary for Regulatory Activities (MedDRA) (Version 22.0). Treatment-emergent adverse events (TEAEs) were defined as any event not present prior to the initiation of treatment or any event already present that worsened in either intensity or frequency following exposure to treatment. | |||||||||
| Arm/Group Title | Placebo-containing MNA | 25 µg Doxorubicin-containing MNA | 50 µg Doxorubicin-containing MNA | 100 µg Doxorubicin-containing MNA | 200 µg Doxorubicin-containing MNA | |||||
| Arm/Group Description | Placebo Placebo-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering a placebo. | D-MNA's containing 25 µg of doxorubicin hydrochloride 25 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 25 µg of doxorubicin hydrochloride. | D-MNA's containing 50 µg of doxorubicin hydrochloride 50 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 50 µg of doxorubicin hydrochloride. | D-MNA's containing 100 µg of doxorubicin hydrochloride 100 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 100 µg of doxorubicin hydrochloride. | D-MNA's containing 200 µg of doxorubicin hydrochloride 200 µg doxorubicin-containing MNA: A 15 x 15 mm array containing 400 tip-loaded, dissolvable microneedles delivering 200 µg of doxorubicin hydrochloride. | |||||
All Cause Mortality |
||||||||||
| Placebo-containing MNA | 25 µg Doxorubicin-containing MNA | 50 µg Doxorubicin-containing MNA | 100 µg Doxorubicin-containing MNA | 200 µg Doxorubicin-containing MNA | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/1 (0%) | |||||
Serious Adverse Events |
||||||||||
| Placebo-containing MNA | 25 µg Doxorubicin-containing MNA | 50 µg Doxorubicin-containing MNA | 100 µg Doxorubicin-containing MNA | 200 µg Doxorubicin-containing MNA | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/1 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Placebo-containing MNA | 25 µg Doxorubicin-containing MNA | 50 µg Doxorubicin-containing MNA | 100 µg Doxorubicin-containing MNA | 200 µg Doxorubicin-containing MNA | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/1 (100%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Application site pain | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Michael J. Fare |
|---|---|
| Organization | SkinJect, Inc. |
| Phone | 203) 533-2050 |
| mfare@skinjectpatch.com |
- SKNJCT-001