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

Sponsor

Alpha Tau Medical LTD. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05657743

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

A unique approach for cancer treatment employing intratumoral diffusing alpha radiation emitter device for advanced pancreatic cancer

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer Unresectable Pancreatic Cancer Metastatic Pancreatic Cancer Pancreatic Adenocarcinoma	Device: Radiation: Diffusing Alpha Radiation Emitters Therapy (DaRT)	N/A

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Nov 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2025

Anticipated Study Completion Date :

Nov 1, 2025

Arms and Interventions

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 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

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 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

Outcome Measures

Primary Outcome Measures

Feasibility - DaRT seed placement [From Day 0]
Feasibility will be determined according to the rate of successful placement of DaRT seeds via imaging
Safety - Adverse events [up to 3 months]
Safety will be determined according to the overall incidence of device related SAE's graded according to CTCAE v5.0 criteria

Secondary Outcome Measures

Efficacy -Alpha DaRT seeds [1 month and 3 months]]
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.
Efficacy-Alpha DaRT seeds [1 month and 3 months]
Change in CA19-9 levels
Efficacy-Alpha DaRT seeds [immediately following the insertion procedure]
Tumor Coverage

Other Outcome Measures

Exploratory objective-Blood samples will be collected for immune response biomarker analyses. Blood samples will be analyzed using FACS and change to the following immune biomarkers will be assessed: CD3, CD4, CD8, CD69, CD137 [1 month]
• Changes in immune markers following treatment with the Alpha DaRT seeds for the treatment of advanced pancreatic cancer. o CD3 CD4 CD8 CD69 CD137
Exploratory objective [1&3 months]
Tumor response using EUS
Blood radioactivity measurements [week 0 and week 7, 1 and 2 months]
Exploratory Objective-Blood samples will be collected and shipped using a designated sample collection kit provided by the Sponsor. The vials will be sent to a central vendor per the instruction provided in the associated laboratory manual.
Urine radioactivity measurements [week 0 and week 7, 1 and 2 months]
Urine samples will be collected and shipped using a designated sample collection kit provided by the Sponsor . the vials will be sent to central vendor per the instruction provided in the associated laboratory manual

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.