Alpha Radiation Emitters Device for the Treatment of Advanced Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
A unique approach for cancer treatment employing intratumoral diffusing alpha radiation emitter device for advanced pancreatic cancer.

Detailed Description
-----------------
This is a prospective, single-center, open label, single arm study. The study is designed to evaluate the feasibility, safety and preliminary efficacy of intratumoral alpha radiation mediated treatment with Alpha 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 4-6 weeks and a long-term follow up phase of 24 months. The total duration of the study will be 24 months from the DaRT insertion procedure. 30 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 24 months post insertion.

Official Title
-----------------
A Feasibility and Safety Study of Intratumoral Diffusing Alpha Radiation Emitters on Advanced Pancreatic Cancer

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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically and/or cytologically proven locally advanced (Stage II or III) or metastatic (Stage IV) pancreatic, adenocarcinoma Inoperable pancreatic cancer due to at least one of the following: a) unresectability, b) metastatic disease, c) medically unfit for surgery ECOG performance status ≤ 2 Measurable lesion per RECIST (version 1.1) criteria Maximum lesion of 4cm in the longest diameter (including primary tumor and regional lymph nodes) ≥ 18 years of age Estimated life expectancy of at least 12 weeks Women of childbearing potential (WOCBP) will have evidence of negative pregnancy test Subjects are willing to sign an informed consent Exclusion Criteria: Prior chemotherapy does not exclude the patient Prior abdominal radiation therapy Concomitant chemotherapy or immunotherapy Borderline resectable pancreatic cancer and medically fit for surgery Connective tissue disease (scleroderma, lupus) 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) Patients not willing to sign an informed consent form Women who are pregnant or lactating

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility - DaRT seed placement | Assessment of the DaRT seed placement within the tumor or less than 5 mm from the tumor using CT imaging on the day of DaRT insertion. | Day 0 (Day of insertion) | 
| Safety - Adverse events | Assessment of the frequency, severity and causality of acute AEs and SAEs related to DaRT seeds insertion. AEs and SAEs will be assessed and graded according to Common Terminology and Criteria for Adverse Events (CTCAE) version 5.0 | 3 months | 
| Safety - Adverse events | Assessment of the frequency, severity and causality of Late AEs and SAEs related to DaRT seeds insertion. AEs and SAEs will be assessed and graded according to Common Terminology and Criteria for Adverse Events (CTCAE) version 5.0. The follow up will be carried out by phone calls every 2 months during the time between 3 to 24 months after DaRT seeds insertion | 3 to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficiency - Short-term effect | Assessment of the objective response rate (ORR) following DaRT seeds insertion using CT scan | 4-6 weeks after DaRT seeds insertion | 
| Tissue damage evaluation | Measuring CA19-9 as a marker to tissue damage. Elevation during treatment, and reduction as a result of tumor ablation. Serum levels of CA 19-9 can be measured using chemiluminescent assay on an Unicel DxI 800 analyzer (BeckmanCoulter, Brea, CA, USA). | Day -14 to 60 days after insertion | 
| Efficiency - Long-term effect | Assessment of the overall survival (OS) following DaRT seeds insertion | 2 years following DaRT seeds insertion | 
| Stent durability | Stent durability will be assessed by the time elapsed from DaRT insertion to the need for follow-up referral for ERCP for stent change due to tumor ingrowth | Day of DaRT insertion up to 24 months. | 
| Change in quality of life: EORTC-QLQ-C30 | Assessment of patient reported health-related Quality of Life (QoL) outcomes after DaRT treatment, using QoL questionnaires EORTC-QLQ-C30 (version 3.0). Scale range in score from 0 (best) to 100(worst). | Day -14 to 60 days after insertion | 
| Change in quality of life: QLQ-PAN26 | Assessment of patient reported health-related Quality of Life (QoL) outcomes after DaRT treatment, using QoL questionnaires QLQ-PAN26. The module comprises 26 questions assessing pain, dietary changes, jaundice, altered bowel habit, emotional problems related to pancreatic cancer, and other symptoms (cachexia, indigestion, flatulence, dry mouth, taste changes). | Day -14 to 60 days after insertion | 

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