Combination treatment for advanced head and neck cancer using radiation and immunotherapy

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial investigates a novel treatment approach for recurrent unresectable or metastatic Head and Neck Squamous Cell Carcinoma (mHNSCC) by combining Diffusing Alpha Radiation Emitters (DaRT) with the checkpoint inhibitor Pembrolizumab. The trial is designed as a prospective, open-label, single-arm study that will assess the safety and efficacy of this combination therapy. Patients will receive DaRT seeds implanted in their target lesions, which will be removed after 15-22 days, while concurrently undergoing treatment with Pembrolizumab. Disease evaluation will occur through radiological imaging every six weeks, starting 42 days after the DaRT insertion.

Why it matters

Who can join: the full rules

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.

Where it's running

• Sharett institute, Hadassah University Hospital - Ein-Kerem
  Jerusalem, Israel Recruiting
• Sheba Medical Center
  Ramat Gan, Israel Recruiting
• Tel-Aviv Medical Center
  Tel Aviv, Israel Not yet recruiting

Study contacts

• Principal investigator: Aron Popovtzer, MD — Sharett institute, Hadassah Medical Center - Ein-Kerem
• Study coordinator: Tami Granot
• Email: TamiG@alphatau.com
• Phone: +972-2-3737-212

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.