A Feasibility and Safety Study of Intratumoral Diffusing Alpha Radiation Emitters for the Treatment of Advanced Pancreatic Cancer

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 advanced pancreatic cancer

Detailed Description
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This is a Prospective, interventional, open label, single arm, multiple center study. The study is designed to evaluate the feasibility and safety of the DaRT seeds for the treatment of advanced pancreatic cancer. The study will be comprised of a screening period, DaRT insertion visit, acute follow-up phase of 4- 8 weeks and a long-term follow up phase of 3 months. The total duration of the study will be 3 months from the DaRT insertion procedure. 15 patients with advanced pancreatic cancer will be recruited by the investigational site. Eligible patients who meet inclusion/exclusion criteria (as assessed during the screening period) will be invited to the site for the procedure of DaRT seeds insertion. The patients will be monitored for a period of 3 months post insertion

Official Title
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A Feasibility and Safety Study of Intratumoral Diffusing Alpha Radiation Emitters for the Treatment of Advanced Pancreatic Cancer

Conditions
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Pancreatic Cancer, Unresectable Pancreatic Cancer, Metastatic Pancreatic Cancer, Pancreatic Adenocarcinoma

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 Histologically and/or cytologically proven locally advanced or metastatic pancreatic adenocarcinoma Patients must have i) received at least one line of chemotherapy OR ii) are medically unfit for further chemotherapy, AND iii) the tumor is still not deemed as resectable with radical surgery or the patient does not wish to go through surgery Target lesion is technically amenable for at least 50% coverage by the Alpha DaRT seeds as determined by the treating physician Interstitial radiation indication validated by a multidisciplinary team Measurable lesion per RECIST (version 1.1) criteria Lesion size ≤ 5 cm in the longest diameter Age ≥18 years old ECOG Performance Status Scale ≤ 2 Life expectancy is more than 6 months WBC ≥ 3500/µl, granulocyte ≥ 1500/µl Platelet count ≥60,000/µl Calculated or measured creatinine clearance ≥ 60cc/min. Calculated or measured creatinine clearance can be≥ 40cc/min given stability of creatinine levels over the past three weeks (at least 1 test per week). AST and ALT ≤ 2.5 X upper limit of normal (ULN) INR < 1.4 for patients not on Warfarin Subjects are willing and able to sign an informed consent form Women of childbearing potential (WOCBP) will have evidence of negative pregnancy test before the Ra-224 implantation and are required to use an acceptable contraceptive method to prevent pregnancy for 3 months after brachytherapy. 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. Exclusion Criteria: Concomitant chemotherapy or immunotherapy within the past 4 weeks Brain metastases Borderline unresectable pancreatic cancer, and/or cases fit for surgical exploration unless patient refuses surgery Known hypersensitivity to any of the components of the treatment. Patients undergoing systemic immunosuppressive therapy excepting intermittent, brief use of systemic corticosteroids. 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. Patients with uncontrolled intercurrent illnesses including, but not limited to an active infection requiring systemic therapy or a known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the trial or interfere with the study endpoints. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Patient requires treatment not specified in this protocol which may conflict with the endpoints of this study including evaluation of response or toxicity of DaRT. Patients do not 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. 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). Breastfeeding women or women of childbearing potential unwilling or unable to use an acceptable contraceptive method to prevent pregnancy for 3 months after RT.

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 radioactive sources [Ra-224 containing stainless-steel 316LVM tubes- (Alpha DaRT 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 |
| --- | --- | --- |
| Feasibility - DaRT seed placement | Feasibility will be determined according to the rate of successful placement of DaRT seeds via imaging | From Day 0 | 
| Safety - Adverse events | Safety will be determined according to the overall incidence of device related SAE's graded according to CTCAE v5.0 criteria | up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy -Alpha DaRT seeds | The secondary objective of the study is to evaluate the efficacy of the Alpha DaRT seeds for advanced pancreatic cancer patients with respect to quality of life and tumor size. | 1 month and 3 months] | 
| Efficacy-Alpha DaRT seeds | Change in CA19-9 levels | 1 month and 3 months | 
| Efficacy-Alpha DaRT seeds | Tumor Coverage | immediately following the insertion procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, Unresectable Pancreatic Cancer, Metastatic Pancreatic Cancer, Pancreatic Adenocarcinoma, Pancreas Neoplasm, Alpha radiation, Pancreas Metastases