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

NCT05047094 | Recruiting

• 1 other identifier: CTP-HNCPI-00
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 3

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

Conditions

Head and Neck Squamous Cell Carcinoma; Skin Cancer; Metastatic Head-and-neck Squamous-cell Carcinoma

Keywords

Squamous Cell Carcinoma; SCC; Skin Cancer; Skin metastasis; HNSCC; Carcinoma, Squamous; Recurrent disease; Alpha radiation; Brachytherapy; Pembrolizumab; Check Point Inhibitor; KEYTRUDA; Immunomodulators

Outcome Measures

Primary Outcomes (1)

• Evaluation of Efficacy of DaRT Treatment in Combination with Pembrolizumab

  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 Outcomes (4)

• Adverse Events

  Until completion of the last study-related procedure, approximately 2 years

• Progression Free Survival (PFS)

  From first dose of Pembrolizumab until progressive disease is recorded (up to 24 months)

• Overall Survival (OS)

  From Pembrolizumab treatment start date to death or lost to follow-up (up to 24 months)

• Duration of Response (DOR)

  From first record of response until the first date recurrent or progressive disease is documented (up to 24 months)

Other Outcomes (1)

• Change in Expression of Immune-Related Biomarkers

  On Day -16, day 0, day 15, and day 68

Study Arms (1)

DaRT seeds

EXPERIMENTAL

Intratumoral Diffusing alpha-emitters Radiation Therapy (DaRT) Seeds in Combination with Standard Treatment of Pembrolizumab

Device: Diffusing Alpha Radiation Emitters Therapy (DaRT); Drug: Pembrolizumab

Interventions

Diffusing Alpha Radiation Emitters Therapy (DaRT) DEVICE

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.

Also known as: DaRT

DaRT seeds

Pembrolizumab DRUG

200 mg administered as an intravenous infusion over 30 minutes every 3 weeks

Also known as: KEYTRUDA

DaRT seeds

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)
• Patients with brain metastases
• Combined Positive Scores (CPS) \<1
• Patients with known contraindications to radiotherapy
• Any prior therapy with anti-PD-L1 (Programmed death-ligand), anti-PD-L2, anti-CTLA-4 (Cytotoxic T lymphocyte antigen) antibody, etc.
• Any history of a sever hypersensitivity reaction to any monoclonal antibody.
• Known hypersensitivity to any of the components of the DaRT.
• Has a known history of active TB (Tuberculosis Bacillus )
• 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.
• Any diagnosis of immunodeficiency or current immunosuppressive therapy including \>10mg/day of prednisone within 14 days of enrollment is not permitted
• 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.
• Patient requires treatment which may conflict with the endpoints of this study including evaluation of response or toxicity of DaRT.
• Has a known history of Human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
• Has known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA \[qualitative\] is detected)

Sponsors & Collaborators

• Alpha Tau Medical LTD.: lead

Study Sites (3)

Sharett institute, Hadassah University Hospital - Ein-Kerem

Jerusalem, 91120, Israel

RECRUITING

Sheba Medical Center

Ramat Gan, Israel

RECRUITING

Tel-Aviv Medical Center

Tel Aviv, Israel

NOT YET RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Skin Neoplasms; Carcinoma, Squamous Cell; Recurrence

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Squamous Cell; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Aron Popovtzer, MD

  Sharett institute, Hadassah Medical Center - Ein-Kerem

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tami Granot

CONTACT

+972-2-3737-212; TamiG@alphatau.com

Liron Dimnik

CONTACT

+972-2-3737-210; LironD@alphatau.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2021
• First Posted: September 16, 2021
• Study Start: November 2, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: December 2, 2025

Record last verified: 2025-11

Locations

IL (3)