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

December 31, 2023 updated by: Alpha Tau Medical LTD.

A Safety and Efficacy Study of Intratumoral Diffusing Alpha Radiation Emitters in Recurrent Unresectable or Metastatic Head and Neck Squamous Cell Carcinoma

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

48

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Israel
      • Jerusalem, Israel, 91120
        • Recruiting
        • Sharett institute, Hadassah University Hospital - Ein-Kerem
        • Contact:
          • Aron Popovtzer, MD
      • Ramat Gan, Israel
      • Tel Aviv, Israel
        • Not yet recruiting
        • Tel-Aviv Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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 Names:
  • DaRT
Drug: Pembrolizumab
200 mg administered as an intravenous infusion over 30 minutes every 3 weeks
Other Names:
  • KEYTRUDA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
From Day 26 to date of documented best response, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Until completion of the last study-related procedure, approximately 2 years
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
From first dose of Pembrolizumab until progressive disease is recorded (up to 24 months)
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.
From Pembrolizumab treatment start date to death or lost to follow-up (up to 24 months)
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.
From first record of response until the first date recurrent or progressive disease is documented (up to 24 months)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
On Day -16, day 0, day 15, and day 68

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alpha Tau Medical LTD.

Investigators

  • Principal Investigator: Aron Popovtzer, MD, Sharett institute, Hadassah Medical Center - Ein-Kerem

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 2, 2021

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

August 29, 2021

First Submitted That Met QC Criteria

September 14, 2021

First Posted (Actual)

September 16, 2021

Study Record Updates

Last Update Posted (Actual)

January 3, 2024

Last Update Submitted That Met QC Criteria

December 31, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTP-HNCPI-00

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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