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

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

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

Study Overview

• Status: Recruiting
• Conditions: Prostate Adenocarcinoma
• Intervention / Treatment: Device: Radiation: Diffusing Alpha Radiation Emitters Therapy (DaRT)

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ester Deutsch; Phone Number: +972-2-3737-212; Email: EsterD@alphatau.com
• Study Contact Backup: Name: Liron Dimnik; Phone Number: +972-2-3737-210; Email: LironD@alphatau.com

Study Locations

• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Care Campus
    • Contact: Tomer Charas, MD; Phone Number: +972-4-777-6505; Email: t_charas@rmc.gov.il
    • Principal Investigator: Tomer Charas, MD
  • Haifa, Israel, 3436212
    • Recruiting
    • Carmel Medical Center
    • Contact: Yuval Freifeld, MD; Phone Number: +972-523453511; Email: yuvalfrei@gmail.com
  • Tel Aviv, Israel
    • Not yet recruiting
    • Tel Aviv Medical Center
    • Contact: Ofer Yossepowitch, MD; Phone Number: 03-6973265; Email: ofery@tlvmc.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DaRT Seeds; Intratumoral Diffusing alpha-emitters Radiation Therapy (DaRT) Seeds	Device: Radiation: Diffusing Alpha Radiation Emitters Therapy (DaRT); 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.

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess DNA damage and repair	Assess DNA damage and repair (biomarker analysis: γH2AX foci, TUNEL, RAD51, RAD50, BRCA1, XRCC2, XRCC6) from baseline to surgery following DaRT seeds insertion.	Day 40 - 60
Assess immune infiltration	Assess immune cell infiltration (biomarker analysis: CD34, TILs) from baseline to surgery following DaRT seeds insertion.	Day 40 - 60
Biochemical response evaluation	Biochemical response evaluation based on PSA levels	Day 19-25, Day 68-82

Collaborators and Investigators

• Sponsor: Alpha Tau Medical LTD.
• Investigators: Principal Investigator: Tomer Charas, M.D, Radiotherapy unit at Rambam Health Care Campus, Israel

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: August 30, 2020
• First Submitted That Met QC Criteria: September 3, 2020
• First Posted (Actual): September 10, 2020

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: December 31, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Prostate adenocarcinoma; Brachytherapy; Alpha radiation
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: CTP-PRST-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No