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. Confirmation obtained within 6 months of planned treatment. Subjects with a tumor size ≤ 7 centimeters in the longest diameter. Targetable lesion must be technically amenable for complete coverage (including margins) by the DaRT seeds Brachytherapy indication validated by a multidisciplinary team Patients who have either failed first-line treatment, or are medically unfit for standard of care (surgery, external-beam radiation therapy or chemotherapy), or refuse standard of care. 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. WBC ≥ 3500/μl, granulocyte ≥ 1500/μl AST and ALT ≤ 2.5 X ULN 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 and are required to use an acceptable contraceptive method to prevent pregnancy for 3 months after brachytherapy. Subjects are willing to sign an informed consent form. Exclusion Criteria: Subject has a tumor of Keratoacanthoma histology. Known hypersensitivity to any of the components of the treatment. Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 12 months. Any medical or psychiatric illness which in the opinion of the investigator would compromise the patient's ability to tolerate this treatment or interfere with the study endpoints. Patients undergoing systemic immunosuppressive therapy excepting intermittent, brief use of systemic corticosteroids Patient requires treatment which may conflict with the endpoints of this study including evaluation of response or toxicity of DaRT 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. Patients must agree to use adequate contraception (vasectomy or barrier method of birth control) prior to study entry, for the duration of study participation and for 3 months after discontinuing therapy. 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>* Other names: DaRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response to DaRT | Assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) | 9-11 weeks post DaRT insertion | 
| Adverse Events | The incidence, frequency, severity and causality of acute adverse events related to the DaRT treatment according to Common Terminology and Criteria for adverse events (CTCAE) version 5.0. | Up to 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in tumor volume | Based on imaging | 9-11 weeks post DaRT insertion | 
| DaRT seeds placement | Assessment by localization of the DaRT seeds in the tumor using CT imaging on the day of DaRT insertion | 1 Day of 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 | Day 15, Day 30, Day 70, Day 180 post DaRT insertion | 
| 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 | Day 30, Day 70, Day 180 post DaRT insertion | 
| Progression Free Survival | Time elapsed from response to disease progression | 24 months post DaRT insertion | 

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