A Clinical Study to Assess the Efficacy and Safety of Alpha DaRT224 for the Treatment of Patients With Recurrent Cutaneous Squamous Cell Carcinoma

January 17, 2024 updated by: Alpha Tau Medical LTD.

A Prospective International Multicenter, Pivotal, Single Arm, Open Label Clinical Study to Assess the Efficacy and Safety of Intratumoral Alpha DaRT224 for the Treatment of Patients With Recurrent Cutaneous Squamous Cell Carcinoma

This is a multi-center clinical study enrolling up to 86 participants. The primary objectives are to determine the objective response rate (ORR) established by the confirmed best overall response (BOR) following intratumoral administration of DaRT - Diffusing Alpha-Emitters Radiation Therapy, as well as to assess the Duration of Response (DOR) 6 months from initial response. Secondary objectives are to assess the safety of DaRT, and to assess the progression free survival (PFS), overall survival (OS), Overall Duration of Response (O-DOR), local control and quality of life (QOL) for patients treated with DaRT.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is a prospective multicenter, pivotal, single arm, open label clinical study to assess the efficacy and safety of intratumoral Alpha DaRT-224 for the treatment of patients with recurrent cutaneous squamous cell carcinoma.

The "Diffusing Alpha-emitter Radiation Therapy (DaRT)", based on the interstitial intratumoral placement of an encapsulated Radium-224 source (3.7 days half-life), is described in this study. These sources release short-lived alpha-emitting atoms into the tumor microenvironment by recoil. DaRT seeds will be inserted into recurrent Squamous Cell Carcinoma (SCC) tumors and will be removed following 14-21 days.

The Objective Response Rate (ORR) will be determined based on the confirmed Best Overall Response (BOR) following DaRT insertion. Duration of Response (DOR) will be assessed for up to 6 months from initial response is documented. Safety will be assessed based on the cumulative incidence rate, severity and outcome of device related Adverse Events (AEs). Classification of AEs will be done according to CTCAE v5.

Study Type

Interventional

Enrollment (Estimated)

86

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
  • United States
    • Arizona
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Withdrawn
        • University of Arkansas
    • California
      • Los Angeles, California, United States, 90095
      • Los Angeles, California, United States, 91010
    • Florida
      • Boca Raton, Florida, United States, 33486
      • Miami, Florida, United States, 33101
      • Miami, Florida, United States, 33176
        • Recruiting
        • Baptist Health South Florida MCI
        • Contact:
      • Tampa, Florida, United States, 33612
    • Georgia
      • Atlanta, Georgia, United States, 30308
    • Iowa
    • Minnesota
      • Rochester, Minnesota, United States, 55905
    • New Jersey
      • Teaneck, New Jersey, United States, 07666
        • Recruiting
        • Holy Name Medical Center
        • Contact:
        • Contact:
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Recruiting
        • New Mexico Cancer Center
        • Contact:
        • Contact:
    • New York
      • Cooperstown, New York, United States, 13326
      • Queens, New York, United States, 11375
        • Recruiting
        • Northwell Health
        • Contact:
      • Uniondale, New York, United States, 11553
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
        • Contact:
    • Ohio
      • Columbus, Ohio, United States, 43210
    • Tennessee
    • Texas
      • Houston, Texas, United States, 77089
        • Recruiting
        • University Cancer & Diagnostic Center
        • Contact:
        • Contact:
    • Virginia
    • Washington
      • Bellevue, Washington, United States, 98004

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. Patients with recurrent cutaneous SCC histologically confirmed who have failed at least first line standard of care therapy who are not indicated for surgery and standard radiation therapy, or non alpha radiation brachytherapy technologies, and for whom no curative systemic treatment is available
  2. Central histopathological confirmation within 6 months of enrollment provided no tumor treatment occurred between the biopsy and enrollment
  3. Measurable disease according to RECIST v 1.1.
  4. Ability to undergo a CT scan
  5. Tumor size ≤7 cm, at the longest diameter.
  6. Single lesion per subject.
  7. Targeted lesion must be technically amenable for complete coverage (including margins) by the DaRT seeds.Targets will be deemed technically amenable for complete coverage if there are entry and exit vectors for placement that are not hindered by bone or major vessels or other vital organs (eg. eye).
  8. Interstitial implant indication validated by multidisciplinary team.
  9. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
  10. Life expectancy ≥12 months.
  11. Subjects male/ female ≥18.
  12. Willing and have the ability to provide signed Informed Consent.
  13. Patients, male and female, with reproductive potential (including women who are menopausal for less than a year and not surgically sterilized), must practice acceptable effective methods of birth control, such as barrier methods, condom or diaphragm with spermicide or abstinence. Birth control should be continued for 3 months after the DaRT insertion visit.
  14. Women with childbearing potential must provide a negative pregnancy test during the screening period and up to V1, prior to the DaRT insertion procedure.

  15. Blood tests values:

    • Leucocytes ≥3000mm3,
    • Absolute neutrophil count ≥1500mm3,
    • Platelets ≥100,000 mm3,
    • Total bilirubin ≤ 1.5xULN (upper limit of normal)
    • Aspartate Aminotransferase (AST) ≤2.5xULN,
    • Serum Glutamic-Oxaloacetic Transaminase (SGOT) ≤2.5xULN,
    • Serum Glutamic-Pyruvic Transaminase (SGPT) ≤2.5xULN,
    • Alkaline Phosphatase ≤2.5xULN.
    • Creatinine ≤ 2.0xULN or Creatinine Clearance ≥60 ml/min.
    • INR (International Normalized Ratio) or Prothrombin time ≤1.5xULN.

Exclusion Criteria:

  1. Distant or nodal metastatic disease (according to the TNM [tumor, nodes , and metastases] staging system - N+ or M1 patients are excluded).
  2. T4 disease or perineural spread of disease
  3. Previously untreated cutaneous SCC indicated for surgery or radiation.
  4. Mucosal, vulvar, anal and penile SCC.
  5. Inability to fully cover the entire volume with DaRT seeds
  6. Inability to place DaRT seeds into tumor due to inaccessibility by presence of bones or major vessels or vital organs
  7. Inability to undergo a CT scan
  8. Patients undergoing systemic immunosuppressive therapy excepting intermittent, brief use of systemic corticosteroids.

  9. Patients receiving any of the following within 4 weeks of enrollment:

    1. Antineoplastic systemic chemotherapy or biological therapy
    2. Immunotherapy
    3. Investigational agents other than the study intervention
    4. Radiation therapy
    5. Live vaccines within 30 days prior to the first dose of trial treatment and while participating in the trial.
  10. Longest tumor diameter >7 cm.
  11. Tumor with keratoacanthoma histology.
  12. Known hypersensitivity to any component of treatment.
  13. Clinically significant cardiovascular disease e.g., cardiac failure of New York Heart Association class III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, history of myocardial infarction in the last 12 months.
  14. Any medical or Psychiatric illness, which in the opinion of the investigator would compromise the patient's ability to tolerate treatment and to adhere to the clinical trial protocol.
  15. Serious medical comorbidities that, in the opinion of the investigator, may affect subject compliance and/or interpretation of treatment safety or effectiveness.
  16. High probability of protocol non-compliance (in opinion of investigator).
  17. 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.
  18. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  19. Patients do not agree to use adequate contraception (vasectomy or barrier method of birth control) prior to study entry and for 3 months after the DaRT insertion visit.
  20. Breastfeeding or pregnant women
  21. Tattoos or other identifying marks which can not be adequately hidden on digital photos

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
DaRT source will be inserted using preplanned radiotherapy parameters and reassessed by volumetric imaging 2-3 weeks after placement and then removed. Objective Response Rate (ORR) will be determined based on confirmed BOR following DaRT insertion.
Device: DaRT seeds
DaRT source will be inserted using preplanned radiotherapy parameters and reassessed by volumetric imaging 2-3 weeks after placement and then removed.
Other Names:
  • DaRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate
Time Frame: From Day 14 until 52 weeks
Objective Response Rate (ORR) of DaRT as treatment for Recurrent SCC established by the confirmed Best Overall Response (BOR), with confirmation at least 4 weeks after initial assessment
From Day 14 until 52 weeks
Duration of Response
Time Frame: 6 months from from first demonstration of CR or PR after Alpha DaRT seeds insertion.
Assess the Duration of Response (DOR) of DaRT as treatment for Recurrent SCC
6 months from from first demonstration of CR or PR after Alpha DaRT seeds insertion.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: Up to 12 months after DaRT seed insertion
Determine Progression Free Survival (PFS) of SCC following DaRT treatment
Up to 12 months after DaRT seed insertion
Overall Survival
Time Frame: Up to 12 months following DaRT insertion
Assess Overall Survival (OS) of Recurrent SCC patients treated with DaRT
Up to 12 months following DaRT insertion
Time of Local Control
Time Frame: Up to 12 months following DaRT insertion
Local control of SCC following DaRT treatment is measured as the time from first recorded response (Complete Response/Partial Response/Stable Disease) to local recurrence up to 12 months or last follow up
Up to 12 months following DaRT insertion
Patients Quality of Life Assessment
Time Frame: On 14 days,12 weeks and 52 weeks following DaRT insertion
Assess patient reported health related quality of life (QOL) outcomes using the Skin Cancer Index (SCI) and Skindex-16 questionnaires
On 14 days,12 weeks and 52 weeks following DaRT insertion
DaRT-related Adverse Events
Time Frame: Up to 12 months following DaRT insertion
Assess the safety of the Alpha DaRT treatment, based on the cumulative incidence rate, severity and outcome of device related AEs. Classification of AEs will be done according to CTCAE v5
Up to 12 months following DaRT insertion
Overall Duration of Response (O-DOR)
Time Frame: Up to 12 months following first reported response
O-DOR Defined as the time from first response (CR or PR) to the date of initial objectively documented progression or death due to any cause, whichever occurs first.
Up to 12 months following first reported response
User experience
Time Frame: On Day 0 (DaRT insertion) and Day 14 (+7) (DaRT removal)
Assess user experience as determined by questionnaire
On Day 0 (DaRT insertion) and Day 14 (+7) (DaRT removal)

Collaborators and Investigators

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

Sponsor

Alpha Tau Medical LTD.

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)

September 21, 2022

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

April 1, 2022

First Submitted That Met QC Criteria

April 11, 2022

First Posted (Actual)

April 12, 2022

Study Record Updates

Last Update Posted (Estimated)

January 18, 2024

Last Update Submitted That Met QC Criteria

January 17, 2024

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTP-SCC-03

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

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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