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A Safety and Efficacy Study for Combinational Treatment of DaRT and Check Point Inhibitor for Recurrent Unresectable or mHNSCC

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ClinicalTrials.gov Identifier: NCT05047094
Recruitment Status : Recruiting
First Posted : September 16, 2021
Last Update Posted : January 3, 2024
Sponsor:
Information provided by (Responsible Party):
Alpha Tau Medical LTD.

Study Description
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Brief Summary:
A unique combinational treatment for cancer employing intratumoral diffusing alpha radiation emitter device with check point inhibitor for recurrent unresectable or metastatic Head and Neck Squamous Cell Carcinoma

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Skin Cancer Metastatic Head-and-neck Squamous-cell Carcinoma Device: Diffusing Alpha Radiation Emitters Therapy (DaRT) Drug: Pembrolizumab Not Applicable

Detailed Description:

This will be a prospective, open-label, one arm, single center two-stage adaptive trial designed to stop for either futility or efficacy after the first stage.

This approach will combine Diffusing Alpha Radiation Emitters seeds implantation along with standard treatment of Pembrolizumab for patients with recurrent unresectable or metastatic Head and Neck Squamous Cell Carcinoma (mHNSCC).

The DaRT seeds will be implanted in the target lesion and removed 15-22 days after implantation. Concurrently, patient will receive standard treatment of Pembrolizumab.

Disease evaluation will be assessed by a radiological imaging every 6 weeks starting at day 42 after the DaRT insertion procedure.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Safety and Efficacy Study of Intratumoral Diffusing Alpha Radiation Emitters in Recurrent Unresectable or Metastatic Head and Neck Squamous Cell Carcinoma
Actual Study Start Date : November 2, 2021
Estimated Primary Completion Date : December 2026
Estimated Study Completion Date : June 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: DaRT seeds
Intratumoral Diffusing alpha-emitters Radiation Therapy (DaRT) Seeds in Combination with Standard Treatment of Pembrolizumab
 Device: 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.
Other Name: DaRT

Drug: Pembrolizumab
200 mg administered as an intravenous infusion over 30 minutes every 3 weeks
Other Name: KEYTRUDA


Outcome Measures
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Primary Outcome Measures :
  1. Evaluation of Efficacy of DaRT Treatment in Combination with Pembrolizumab [ Time Frame: From Day 26 to date of documented best response, assessed up to 24 months ]
    Assessed via the Confirmed Best Overall Response (BOR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1)


Secondary Outcome Measures :
  1. Adverse Events [ Time Frame: Until completion of the last study-related procedure, approximately 2 years ]
    Assessment of the frequency, severity and causality of acute adverse events related to the DaRT treatment in combination with immune checkpoint inhibitors. This will be assessed and graded according to Common Terminology and Criteria for Adverse Events (CTCAE) version 5.0. (graded 1-5, 1 is mild and 5 is death)

  2. Progression Free Survival (PFS) [ Time Frame: From first dose of Pembrolizumab until progressive disease is recorded (up to 24 months) ]
    PFS will be defined as time from Pembrolizumab treatment start date to progressive disease according to RECIST v1.1 or death due to any cause, whichever occurs first

  3. Overall Survival (OS) [ Time Frame: From Pembrolizumab treatment start date to death or lost to follow-up (up to 24 months) ]
    Defined as the time from Pembrolizumab treatment start date to death due to any cause or lost to follow up.

  4. Duration of Response (DOR) [ Time Frame: From first record of response until the first date recurrent or progressive disease is documented (up to 24 months) ]
    Duration of response is defined as the interval from the time measurement criteria are first met for Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (whichever is first recorded) until the first date recurrent or progressive disease is objectively documented.


Other Outcome Measures:
  1. Change in Expression of Immune-Related Biomarkers [ Time Frame: On Day -16, day 0, day 15, and day 68 ]
    This study will assess the change in immune related biomarkers in peripheral blood using Fluorescence-activated cell sorting (FACS) analysis. These biomarkers include: CD3, CD4, CD8, CD69, CD137


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Pathologically confirmed, metastatic, or recurrent unresectable squamous cell carcinoma of the head and neck.
  2. Ability to provide tissue sample, either from an archive or undergo another biopsy to provide a fresh sample
  3. Targetable lesion must be technically amenable for the DaRT seeds implantation
  4. Brachytherapy indication validated by a multidisciplinary team
  5. Targetable lesion according to RECIST v1.1
  6. Age ≥ 18 years old
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status Scale ≤ 2
  8. Subjects' life expectancy is more than 6 months
  9. White Blood Count (WBC) ≥ 3500/µl, granulocyte ≥ 1500/µl
  10. Platelet count ≥ 100,000/µl
  11. Hemoglobin ≥ 9 g/dl
  12. Calculated or measured creatinine clearance ≥ 60 cc/min
  13. Aspartate Aminotransferase (AST) and Alanine Transaminase (ALT) ≤ 2.5 X Upper Limit of Normal (ULN) or ≤ 5 X ULN for subjects with liver metastases
  14. International normalized ratio (INR) <1.4 for patients not on Warfarin
  15. Subjects are willing and able to sign an informed consent form
  16. 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.

Exclusion Criteria:

  1. Previous treatment for metastatic disease (for recurrent unresectable disease, previous treatment is allowed given that 6 months had elapsed from completion of treatment for primary disease)
  2. Patients with brain metastases
  3. Combined Positive Scores (CPS) <1
  4. Patients with known contraindications to radiotherapy
  5. Any prior therapy with anti-PD-L1 (Programmed death-ligand), anti-PD-L2, anti-CTLA-4 (Cytotoxic T lymphocyte antigen) antibody, etc.
  6. Any history of a sever hypersensitivity reaction to any monoclonal antibody.
  7. Known hypersensitivity to any of the components of the DaRT.
  8. Has a known history of active TB (Tuberculosis Bacillus )
  9. 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.
  10. Any diagnosis of immunodeficiency or current immunosuppressive therapy including >10mg/day of prednisone within 14 days of enrollment is not permitted
  11. 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.
  12. 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.
  13. Patient requires treatment which may conflict with the endpoints of this study including evaluation of response or toxicity of DaRT.
  14. Has a known history of Human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
  15. Has known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA [qualitative] is detected)
  16. Pregnancy or lactation.
  17. Patients must agree to use adequate contraception (abstinence, barrier method of birth control, or any other medically acceptable form of contraception) prior to study entry, for the duration of study participation and for 6 months after last dose of Pembrolizumab.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05047094


Contacts
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Contact: Tami Granot +972-2-3737-212 TamiG@alphatau.com
Contact: Liron Dimnik +972-2-3737-210 LironD@alphatau.com

Locations
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Israel
Sharett institute, Hadassah University Hospital - Ein-Kerem Recruiting
Jerusalem, Israel, 91120
Contact: Aron Popovtzer, MD         
Sheba Medical Center Not yet recruiting
Ramat Gan, Israel
Contact: Iris Gluck, MD    052-6669142    Iris.gluck@sheba.health.gov.il   
Tel-Aviv Medical Center Not yet recruiting
Tel Aviv, Israel
Contact: Inbar Finkel, MD    03-6973494    Inbarfi@tlvmc.gov.il   
Sponsors and Collaborators
Alpha Tau Medical LTD.
Investigators
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Principal Investigator: Aron Popovtzer, MD Sharett institute, Hadassah Medical Center - Ein-Kerem
More Information
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Responsible Party: Alpha Tau Medical LTD.
ClinicalTrials.gov Identifier: NCT05047094    
Other Study ID Numbers: CTP-HNCPI-00
First Posted: September 16, 2021    Key Record Dates
Last Update Posted: January 3, 2024
Last Verified: September 2023

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Alpha Tau Medical LTD.:
Squamous Cell Carcinoma
SCC
Skin Cancer
Skin metastasis
HNSCC
Carcinoma, Squamous
Recurrent disease
 Alpha radiation
Brachytherapy
Pembrolizumab
Check Point Inhibitor
KEYTRUDA
Immunomodulators
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Skin Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
 Head and Neck Neoplasms
Neoplasms by Site
Skin Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action