Alpha Radiation Emitters Device for the Treatment of of Malignant Cutaneous Tumors

Study Overview
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Brief Summary
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A unique approach for cancer treatment employing intratumoral diffusing alpha radiation emitter device for Malignant Cutaneous Tumors

Detailed Description
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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).

Official Title
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A Safety and Effectiveness Study of Intratumoral Diffusing Alpha Radiation Emitters for the Treatment of Malignant Cutaneous Tumors

Conditions
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Cutaneous Metastasis, Skin Cancer, Cutaneous Tumor

Intervention / Treatment
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* Device: DaRT- Diffusing Alpha-emitters Radiation Therapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DaRT Seeds Intratumoral Diffusing alpha-emitters<br>An intratumoral insertion of securely fixed seeds loaded with Radium-224. The seeds release by recoil short-lived alpha-emitting atoms into the tumor. | Device: DaRT- Diffusing Alpha-emitters Radiation Therapy<br>* Seed(s) loaded with Radium-224 for local intratumoral irradiation with the destructive power of alpha particles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The objective response rate to DaRT treatment | Assessment of tumor response rate using the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) | up to 9-11 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor volume | Assessment of the reduction in tumor volume based on imaging tests | up to 9-11 weeks | 
| DaRT seeds placement | Assessment of the DaRT seed placement by localization of the DaRT seed in the tumor using CT imaging | Day of DaRT insertion procedure | 
| Change in quality of life as assessed by the Skindex-16 questionnaire | Assessment of patient reported health-related Quality of Life (QoL) outcomes using the Skindex-16 questionnaire | up to 9-11 weeks | 
| Disease-Free Survival (DFS) rate | Assessment of Disease-Free Survival | up to 24 months | 
| Change in quality of life as assessed by the Skin Cancer Index (SCI) questionnaire | Assessment of patient reported health-related Quality of Life (QoL) outcomes using the Skin Cancer Index (SCI) questionnaire. | up to 9-11 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous Cell Carcinoma, Basal Cell Carcinoma, Skin Cancer, Skin Metastasis, Superficial Sarcoma, Alpha Radiation, Cutaneous Lesion, Brachytherapy, Radiotherapy, Lentigo maligna melanoma, Carcinosarcom, scalp cancer, Lip cancer, Eyelid cancer, SCC