Neoadjuvant Interstitial Brachytherapy Using Diffusing Alpha Emitters Radiation Therapy in Men With Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
A unique approach for cancer treatment employing intratumoral diffusing alpha radiation emitter device as a neo-adjuvant therapy in men with prostate cancer

Detailed Description
-----------------
The study is planned as a prospective, open-label, one arm, single center trial, designed to assess the feasibility and safety of intratumoral DaRT seeds implantation for the treatment of local prostate cancer prior to surgery. 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. Prostate lesions with histopathological confirmation of adenocarcinoma will be treated using DaRT seeds in a neo-adjuvant setting. Feasibility will be assessed by the successful delivery of DaRT seeds into the intratumoral environment. In addition, objective response rate will be assessed both by imaging and pathology.

Official Title
-----------------
A Feasibility of Neoadjuvant Interstitial Brachytherapy (Ibt) Using Diffusing Alpha Emitters Radiation Therapy (Dart) Seeds in Men With Prostate Cancer

Conditions
-----------------
Prostate Adenocarcinoma

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pathologically confirmed, previously untreated, resectable prostate adenocarcinoma Ability to provide tissue sample from the target or its vicinity, either from an archive or undergo another biopsy to provide a fresh sample Medically fit for surgery Targetable lesion must be technically amenable for complete coverage (including 3-5mm margins) by the DaRT seeds Targetable lesion by either PSMA PET-CT according to PERCIST v1.0 OR by multiparametric MRI according RECIST v1.1 Patients must be willing to undergo imaging before and after treatment with DaRT (prior to surgery) Lesion size ≤ 3 cm in the longest diameter Age ≥ 18 years old ECOG Performance Status Scale ≤ 1 Subjects' life expectancy is more than 6 months WBC ≥ 3500/μl, granulocyte ≥ 1500/μl Platelet count ≥ 100,000/μl Calculated or measured creatinine clearance ≥ 60 cc/min AST and ALT ≤ 2.5 X ULN INR <1.4 for patients not on Warfarin Subjects are willing and able to sign an informed consent form Exclusion Criteria: Documented evidence of distant metastases Prior TURP or prostate surgery Prior pelvic radiation Any prior pelvic malignancy or other malignancy in the last 5 years, except for cured non-melanoma skin cancer Inability to undergo MRI (i.e. permanent implanted device incompatible with MRI) 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 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 DaRT implant procedure 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

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

Sexes Eligible for Study
-----------------
Male

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of intratumoral DaRT seeds implantation | To evaluate the feasibility of intratumoral insertion of DaRT seeds into prostate adenocarcinoma in the neoadjuvant setting. Feasibility will defined as the successful delivery of DaRT. | Study visit 'Day 0' | 
| Safety of intratumoral DaRT seeds implantation | To evaluate the safety of intratumoral insertion of DaRT seeds into prostate adenocarcinoma in the neoadjuvant setting. To evaluate the safety of intratumoral insertion of DaRT seeds into prostate adenocarcinoma in the neoadjuvant setting by the frequency and severity of acute adverse events related to DaRT. Adverse events will be assessed and graded according to Common Terminology and Criteria for adverse events (CTCAE) version 5.0. | Study visit 'Day 0' | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological ORR | To asses the percentage of patients whose cancer shrinks or disappears after treatment using a biopsy from removed prostate. | Week 4-6 | 
| Radiological ORR | Radiological response rate according to PSMA-PET/ multiparametric MRI (SUV change/T2 weighting) through comparison with baseline imaging as assessed by RECIST or PERCIST. | 1 Week prior to surgery | 
| Change in quality of life | Change in disease related QoL using the EPIC questionnaires from baseline to prior to surgery | Screening. Day 22. | 
| Change in quality of life | Change in disease related QoL using the IPSS questionnaires from baseline to prior to surgery | Screening. Day 22. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prostate adenocarcinoma, Alpha radiation, Brachytherapy