Alpha Radiation Emitters Device (DaRT) for the Treatment of of Malignant Cutaneous Tumors

This will be a prospective, open label, single arm, multi- center study, assessing the safety and effectiveness of diffusing alpha emitters radiation therapy (DaRT) delivered through radioactive seeds inserted into the tumor.

This approach combines the advantages of local intratumoral irradiation of the tumor, as used in conventional brachytherapy, with the power of the alpha radiation emitting atoms, that will be introduced in quantities considerably lower than radiation therapy already used in patients.

Cutaneous lesions with histopathological confirmation of malignancy will be treated using DaRT seeds.

Reduction in tumor size 9-11 weeks following DaRT insertion will be assessed. Safety will be assessed by the frequency, severity and causality of all Adverse Events (AE).

Inclusion criteria

• Subjects with histopathological confirmation of newly diagnosed (Cohort A) or locally recurrent (Cohort B) malignant cutaneous lesions of the following histopathologies:

• SCC
• BCC
• Lentigo maligna melanoma (Dubreuilh melanoma)
• Carcinosarcoma
• Acceptable tumor locations include the following:

• Skin (facial, scalp, extremities, torso)
• Lips
• Eyelids
• Subjects with a tumor size ≤ 7 centimeters in the longest diameter.
• Target lesion technically amenable for full tumor coverage with the Alpha DaRT seeds.
• Measurable disease according to RECIST v1.1.
• Subjects over 18 years old.
• Subjects' ECOG Performance Status Scale is < 2.
• Subjects' life expectancy is more than 6 months.
• Platelet count ≥100,000/mm3.
• International normalized ratio of prothrombin time ≤1.8.
• Women of childbearing potential (WOCBP) will have evidence of negative pregnancy test.
• Subjects are willing to sign an informed consent form

Exclusion criteria

• Subject has a tumor with histology of one of the following:

• Keratoacanthoma
• Merkel cell carcinoma
• Sarcoma other than carcinosarcoma
• Metastatic disease (according to the TNM staging system - M1 patients are excluded)
• Patients with significant comorbidities that the treating physician deems may conflict with the endpoints of the study (e.g., poorly controlled autoimmune diseases, vasculitis, etc.).
• Patients undergoing systemic immunosuppressive therapy excepting intermittent, brief use of systemic corticosteroids.
• Volunteers participating in another interventional study in the past 30 days which might conflict with the endpoints of this study or the evaluation of response or toxicity of DaRT.
• High probability of protocol non-compliance (in opinion of investigator).
• Subjects not willing to sign an informed consent.
• Women who are pregnant or breastfeeding.