Cutaneous Squamous Cell Carcinoma, Skin Cancers - Squamous Cell Carcinoma
Conditions
Keywords
micro-needle array, doxorubicin, patch
Brief summary
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.
Detailed description
This study will evaluate a novel approach to the treatment of cutaneous squamous cell cancer (cSCC) of patients diagnosed previously by skin biopsy with cSCC utilizing a dissolvable microneedle array (MNA) delivery device that is used to directly and specifically deliver a drug to the tumor microenvironment for skin cancer therapy. The investigators will utilize MNAs to deliver a well-characterized, potent chemotherapeutic agent (doxorubicin) to kill topically accessible, cutaneous SCC cells. In addition to directly killing cancer cells, doxorubicin is known to induce an immunologic cell death with the potential to simultaneously convert a cutaneous neoplasm into a highly potent patient specific immunogen capable of inducing innate, adaptive, and tumor specific effector and memory immune responses. Importantly, doxorubicin is currently in clinical use with a well-established safety profile. It is anticipated that use of the MNA-Doxorubicin (MNA-D) delivery system will enable direct and specific delivery of chemotherapy to the tumor, thereby avoiding any potential for systemic toxicity. The study will be conducted using two groups: one group will consist of patients with immunocompetent immune systems and the second group will consist of patients who have had an organ transplant and are considered immunoincompetent.efficacy and safety evaluation. The first phase is now completed. Following a screening/baseline phase, the MNA-D patch application and assessment visits will occur from week 0 through week 3, followed by a rest week and at week 5, up to week 8, a final follow up visit will take place. At the final follow up visit, the remaining cSCC lesion will be removed in a standard of care manner to ensure that all tissue margins are clear of the cSCC.
Interventions
DRUGMicroneedle Array Doxorubicin (MNA-D)
The Microneedle array patch is loaded/prepared with a total dose of 50 micrograms of Doxorubicin and is applied to a single selected cSCC remnant for a period of 20 minutes for a total of 4 weekly applications
Sponsors
Falo, Louis, MD
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an open-label, comparative 2-cohort design
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects must have a histological diagnosis of cSCC based upon a skin biopsy. 2. Subjects must have resectable stage I-III disease. \- Measures ≥5 millimeters (mm; post-biopsy) and \<100 mm in longest diameter 3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2 4. Subjects must have an expected survival of greater than or equal to 12 months. 5. Subjects must not be on any other investigational device/drug treatment. 6. Subjects must be willing to adhere to the instructions of the Investigator and his research team and sign an Informed Consent Form prior to entry into the study. 7. Subjects must have the following pretreatment laboratory parameters: granulocytes ≥1,500/mm3; platelets \>50,000/mm3; serum creatinine ≤2X the upper limit of normal (ULN); AST, ALT ≤3X the ULN, bilirubin ≤1.5X ULN unless Gilbert's disease then ≤3X ULN. 8. Subjects must be at least 18 years of age and must be able to understand the written informed consent/assent document. 9. Subjects must have no evidence of active infection, regardless of the degree of severity or localization. Subjects with active infections (whether or not they require antibiotic therapy) may be eligible for study participation after complete resolution of the infection. Subjects on antibiotic therapy must be off antibiotics before beginning treatment. 10. Subjects must not receive any other treatment for cSCC except emollients of subject's choice without topical steroids, anti-fungal or antibacterial topical preparations. 11. Subjects with multiple cSCC may re-enroll in the study if greater than 4 weeks elapses between courses and if all other inclusion/
Exclusion criteria
are met. 12. Patients with HIV infection with CD4+ T-cell (CD4+) counts ≥ 350 cells/uL will be eligible for the study. Patients without a history of AIDS-defining opportunistic infections will be eligible for the study. 13. Subjects must be willing/able to comply with standard of care measures for subjects with cSCC such as sun avoidance and sun protection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events grade 2 or higher to evaluate safety of MNA-D patches in cSCC | Baseline up to week 8 | Evaluated by assessing adverse events grade 2 or higher related to the MNA-D intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline of local response to the MNA-D patch | Baseline and follow up (weeks 5-8) | Percentage of tumor clearance of the area directly under the patch is measured.. |
| Tumor clearance from baseline of locoregional (total area of the index lesion) response to the MNA-D Patch | Baseline and follow up (weeks 5-8) | Percentage of tumor clearance from the entire cSCC lesion treated by the patch is measured including the area directly covered by the MNA and uncovered area of the treated lesion. . |
| Quantitative pathologic evaluation of tumor depth | Follow up period (weeks 5-8) | To provide a quantitative assessment of cSCC reduction after treatment, the remnant of cSCC tumors will be excised at week 5-8 and evaluated independently by 2 dermatopathologists in the blinded fashion. The depth of the cSCC will be measured. |
| Flow cytometry quantitative biologic response evaluation in blood | Baseline and follow up (weeks 5-8) | Flow cytometry will evaluate in-vivo tumor immune responses in the blood and will analyze total immune activity for increases and/or decreases in T cell populations of interest and other immune cells (e.g., MDSCs, NK cells, B cells, macrophages, dendritic cells) that could influence the frequency and phenotype of these populations. |
| Flow cytometry quantitative biologic response evaluation in tumor tissue | Baseline and follow up (weeks 5-8) | Flow cytometry will evaluate in-vivo tumor immune responses in the excised tumor tissue and will analyze total immune infiltrates for increases and/or decreases in T cell populations of interest and other immune cells (e.g., MDSCs, NK cells, B cells, macrophages, dendritic cells) that could influence the frequency and phenotype of these populations. |
| Percentage of reduction in cSCC tumor | Baseline and follow up (weeks 5-8) | To provide a quantitative assessment of cSCC reduction after treatment, the remnant of cSCC tumors will be excised at week 5-8 and evaluated independently by 2 dermatopathologists in the blinded fashion. The percentage of reduction in comparison to the original tumor will be reported. |
| Luminex quantitative biologic response in blood | Baseline and follow up (weeks 5-8) | Luminex will evaluate in-vivo tumor immune responses for 65 selected serum biomarkers using a multiplex Luminex 100 (Bio-Rad Bio-Plex System) including G-CSF, GM-CSF, IFN-α, IFN-γ, IL-1β, IL-1RA, IL-2, IL-2R, IL-4, IL-5, IL-6, IL- 7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, TNF-α, eotaxin, IP-10, MCP-1, MIG, MIP-1α, MIP-1β, RANTES, EGF, FGF-basic, HGF, and VEGF. |
| Serum SCC-Ag quantitative biologic response in blood | Baseline and follow up (weeks 5-8) | Serum SCC-Ag levels will evaluate in-vivo tumor immune responses in the blood |
| Luminex quantitative biologic response evaluation in tumor tissue | Baseline and follow up (weeks 5-8) | Luminex will evaluate in-vivo tumor tissue immune responses for 65 selected serum biomarkers using a multiplex Luminex 100 (Bio-Rad Bio-Plex System) including G-CSF, GM-CSF, IFN-α, IFN-γ, IL-1β, IL-1RA, IL-2, IL-2R, IL-4, IL-5, IL-6, IL- 7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, TNF-α, eotaxin, IP-10, MCP-1, MIG, MIP-1α, MIP-1β, RANTES, EGF, FGF-basic, HGF, and VEGF. |
| Serum SCC-AG quantitative biologic response evaluation in tumor tissue | Baseline and follow up (weeks 5-8) | Serum SCC-Ag levels will evaluate in-vivo tumor immune responses in the excised tumor tissue from baseline to week 8 |
Countries
United States
Contacts
CONTACTCharity L Ruhl, LPN
CONTACTNicolena Verardi
PRINCIPAL_INVESTIGATOROleg E Akilov, MD, PhD
University of Pittsburgh
Outcome results
None listed