Alpha Radiation Emitters Device (DaRT) for the Treatment of Cutaneous, Mucosal or Superficial Soft Tissue Neoplasia.

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 superficial cutaneous, mucosal or soft tissue neoplasia

Detailed Description
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This will be a prospective, open label, single arm, controlled study, assessing the safety and efficacy 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. Superficial lesions with histopathological confirmation of malignancy will be treated using DaRT seeds. Reduction in tumor size 70 days after DaRT insertion will be assessed. Safety will be assessed by the incidence, severity and frequency 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, Mucosal or Superficial Soft Tissue Neoplasia

Conditions
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Skin Cancer, Mucosal Neoplasm of Oral Cavity, Soft Tissue Neoplasm

Intervention / Treatment
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* Device: Radiation: Diffusing Alpha Radiation Emitters Therapy (DaRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with histopathological confirmation of primary or secondary malignant cutaneous neoplastic lesions, or oral cavity mucosal tumors, or superficial soft tissue sarcoma. Subjects with a tumor size ≤ 7 centimeters in the longest diameter. 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. Creatinine ≤1.9 mg/dL. 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 of Keratoacanthoma histology. 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<br>Intratumoral Diffusing alpha-emitters Radiation Therapy (DaRT) Seeds | Device: Radiation: Diffusing Alpha Radiation Emitters Therapy (DaRT)<br>* An intratumoral insertion of a seed(s), loaded with Radium-224, securely fixed in the seeds. The seeds release by recoil into the tumor short-lived alpha-emitting atoms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response to DaRT | Assessment of the rate of malignant cutaneous, mucosal or superficial soft tissue tumors response using the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) | 9-11 weeks after DaRT seed insertion. | 
| Adverse Events | The incidence, frequency, severity and causality of acute adverse events related to the DaRT treatment | Time Frame: 9-11 weeks post DaRT insertion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the reduction in tumor volume | Assessment of the reduction in tumor volume based on CT / PET-CT measured tumor volume | 9-11 weeks follow-up visit. | 
| DaRT seeds placement. | Assessment of the DaRT seeds placement by localization of the DaRT seeds in the tumor using CT imaging on the day of DaRT insertion. | Day of insertion procedure. | 
| Change in quality of life | Assessment of patient reported health-related Quality of Life outcome after DaRT, using QoL questionnaire Skindex-16 questionnaire score. An overall score ranging from 0 (best) to 100 (worst). | Screening, DaRT removal and day 70 visits. | 
| Change in quality of life | Assessment of patient reported health-related Quality of Life outcome after DaRT, using QoL questionnaire Skin Cancer Index (SCI) questionnaire score. An overall score ranging from 0 (best) to 100 (worst). | Screening, DaRT removal and day 70 visits. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCC, Squamous Cell Carcinoma, Skin Cancer, Skin metastasis, HNSCC, Carcinoma, Squamous, CMN, Basal cell carcinoma, Superficial sarcoma, Kaposi sarcoma, Alpha radiation, Cutaneous lesion, Tongue cancer, Lip cancer