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Alpha Radiation Emitters Device for the Treatment of Pancreatic Cancer Emitters for the Treatment of Locally Advanced Pancreatic Cancer

Primary Purpose

Pancreatic Cancer, Unresectable Pancreatic Cancer, Pancreatic Adenocarcinoma

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
DaRT seeds insertion
Sponsored by
Alpha Tau Medical LTD.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring pancreatic cancer, Unresectable Pancreatic Cancer, Pancreatic Adenocarcinoma, Alpha radiation, Pancreas Cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Histologically and/or cytologically proven NCCN locally advanced PC Patients must have i) received at least one line of chemotherapy (any kind) 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. DaRT indication validated by a multidisciplinary team. Measurable lesion per RECIST (version 1.1) criteria TC at Verona's center (not been over a month) 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 ≥ 30cc/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 Prior radiation therapy to the pancreas CA 19-9 > 1000 Units/ml Fit for surgical exploration unless the 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 (not including cholangitis) 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    DaRT Seeds

    Arm Description

    Intratumoral Diffusing alpha-emitters Radiation Therapy (DaRT) Seeds

    Outcomes

    Primary Outcome Measures

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

    Secondary Outcome Measures

    To evaluate the Efficacy of the Alpha DaRT seeds for locally advanced pancreatic cancer
    Local control evaluation according to RECIST v1.1
    To evaluate the Efficacy of the Alpha DaRT seeds by measuring the CA-19-9 markers levels
    Change in CA 19-9 levels
    Efficacy - to evaluate what is the percent of the Tumor Coverage by the Alpha DaRT seeds
    Tumor Coverage
    Efficacy- Alpha DaRT seeds
    Overall incidence of device-related SAE's graded according to CTCAE v5.0 criteria

    Full Information

    First Posted
    August 17, 2023
    Last Updated
    September 5, 2023
    Sponsor
    Alpha Tau Medical LTD.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06026943
    Brief Title
    Alpha Radiation Emitters Device for the Treatment of Pancreatic Cancer Emitters for the Treatment of Locally Advanced Pancreatic Cancer
    Official Title
    A Feasibility and Safety Study of Intratumoral Diffusing Alpha Radiation Emitters for the Treatment of Locally Advanced Pancreatic Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 2024 (Anticipated)
    Primary Completion Date
    January 2026 (Anticipated)
    Study Completion Date
    January 2028 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Alpha Tau Medical LTD.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    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, interventional, single-center, open label, single arm study. The study is designed to evaluate the feasibility and Safety of Intratumoral Diffusing Alpha Radiation Emitters for the Treatment of Locally Advanced Pancreatic Cancer The study will be comprised of a screening period, DaRT insertion visit, 3 months follow up per subject and 2 years for accrual and trial completion. The total duration of the study will be 24 months from the DaRT insertion procedure. 15 patients with a safety interim analysis after the 5 first patients . 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pancreatic Cancer, Unresectable Pancreatic Cancer, Pancreatic Adenocarcinoma
    Keywords
    pancreatic cancer, Unresectable Pancreatic Cancer, Pancreatic Adenocarcinoma, Alpha radiation, Pancreas Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    15 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    DaRT Seeds
    Arm Type
    Experimental
    Arm Description
    Intratumoral Diffusing alpha-emitters Radiation Therapy (DaRT) Seeds
    Intervention Type
    Device
    Intervention Name(s)
    DaRT seeds insertion
    Other Intervention Name(s)
    Device: Radiation: Diffusing Alpha Radiation Emitters Therapy (DaRT)
    Intervention Description
    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
    Primary Outcome Measure Information:
    Title
    Feasibility- DaRT seed placement
    Description
    Feasibility will be determined according to the rate of successful placement of DaRT seeds via imaging
    Time Frame
    Immediately following the insertion procedure
    Title
    Safety- Adverse events, Safety will be determined according to the overall incidence of device-related SAE's graded according to CTCAE v5.0 criteria
    Description
    Safety will be determined according to the overall incidence of device-related SAE's graded according to CTCAE v5.0 criteria
    Time Frame
    from DaRT-insertion up to 48 hours
    Secondary Outcome Measure Information:
    Title
    To evaluate the Efficacy of the Alpha DaRT seeds for locally advanced pancreatic cancer
    Description
    Local control evaluation according to RECIST v1.1
    Time Frame
    1 months and 3 months
    Title
    To evaluate the Efficacy of the Alpha DaRT seeds by measuring the CA-19-9 markers levels
    Description
    Change in CA 19-9 levels
    Time Frame
    1 months and 3 months
    Title
    Efficacy - to evaluate what is the percent of the Tumor Coverage by the Alpha DaRT seeds
    Description
    Tumor Coverage
    Time Frame
    immediately following the insertion procedure]
    Title
    Efficacy- Alpha DaRT seeds
    Description
    Overall incidence of device-related SAE's graded according to CTCAE v5.0 criteria
    Time Frame
    from DaRT-insertion up to initiation of a possible postablation therapy or up to a maximum three months
    Other Pre-specified Outcome Measures:
    Title
    Exploratory Objective -to evaluate the changes in the immune markers by Blood samples for immune response
    Description
    Changes in immune markers following treatment ,These biomarkers include: CD3 CD4 CD8 CD69 CD137
    Time Frame
    1 month

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    120 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Histologically and/or cytologically proven NCCN locally advanced PC Patients must have i) received at least one line of chemotherapy (any kind) 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. DaRT indication validated by a multidisciplinary team. Measurable lesion per RECIST (version 1.1) criteria TC at Verona's center (not been over a month) 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 ≥ 30cc/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 Prior radiation therapy to the pancreas CA 19-9 > 1000 Units/ml Fit for surgical exploration unless the 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 (not including cholangitis) 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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Liron Dimnik
    Phone
    +972-2-3737-7000
    Email
    LironD@alphatau.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Salvatore Paiella, MD
    Organizational Affiliation
    Pancreas Institute - Integrated University Hospital of Verona
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Alpha Radiation Emitters Device for the Treatment of Pancreatic Cancer Emitters for the Treatment of Locally Advanced Pancreatic Cancer

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