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

NCT ID: NCT05047094

Last Updated: 2025-12-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-02
• Study Completion Date: 2027-06-30

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

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DaRT seeds

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

Group Type: EXPERIMENTAL

Diffusing Alpha Radiation Emitters Therapy (DaRT)

Intervention Type: 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.

Pembrolizumab

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DEVICE

Pembrolizumab

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

Intervention Type: DRUG

Other Intervention Names

DaRT; KEYTRUDA

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alpha Tau Medical LTD.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aron Popovtzer, MD

Role: PRINCIPAL_INVESTIGATOR

Sharett institute, Hadassah Medical Center - Ein-Kerem

Locations

Sharett institute, Hadassah University Hospital - Ein-Kerem

Jerusalem, , Israel

Site Status: RECRUITING

Sheba Medical Center

Ramat Gan, , Israel

Site Status: RECRUITING

Tel-Aviv Medical Center

Tel Aviv, , Israel

Site Status: NOT_YET_RECRUITING

Countries

Israel

Central Contacts

Tami Granot

Role: CONTACT

TamiG@alphatau.com

+972-2-3737-212

Liron Dimnik

Role: CONTACT

LironD@alphatau.com

+972-2-3737-210

Facility Contacts

Aron Popovtzer, MD

Role: primary

Iris Gluck, MD

Role: primary

Iris.gluck@sheba.health.gov.il

052-6669142

Inbar Finkel, MD

Role: primary

Inbarfi@tlvmc.gov.il

03-6973494

Other Identifiers

CTP-HNCPI-00

Identifier Type: -

Identifier Source: org_study_id