Study on the Efficacy of Radiotherapy Added to Pembrolizumab in Newly Diagnosed Metastatic Head and Neck Cancers

• Status: Recruiting
• Trial end date: 2029-09-15
• Target enrollment: 0
• Participant gender: All

Summary

Trial evaluating the efficacy of radiotherapy added to pembrolizumab compared to pembrolizumab alone for patients with newly diagnosed head and neck carcinoma with metastases

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: UNICANCER
• Collaborators: GORTEC; National Cancer Institute, France
• Treatments: Pembrolizumab

Criteria

Inclusion Criteria:

1. Patient must have signed a written informed consent form prior to any study specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.

2. Newly diagnosed histologically confirmed squamous cell carcinoma of head and neck (oral cavity, oropharynx, hypopharynx, and larynx) with histologically confirmed distant metastases at presentation (T1-4 N0-3 M1)

3. Eligible for treatment by pembrolizumab according to the European Marketing Authorization

4. Patient ≥18 years old

5. Performance status: 0-1 (WHO)

6. Combined Positive Score (CPS) ≥1 for primary tumor (as determined per local practice)

7. Subjects must have at least one measurable lesion as per RECIST v1.1 to assess efficacy

8. Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within one month prior to initiation of study treatment:

1. Absolute neutrophil count ≥1.5 × 10⁹/L

2. Platelet ≥100 × 10⁹/L

3. Hemoglobin ≥90 g/L

4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT), ≤3 × upper limit of normal (ULN), (unless documented liver metastases where ≤5 x ULN is permitted)

5. Bilirubin ≤1.5 × ULN.

6. Serum albumin ≥25 g/L

7. Creatinine clearance ≥30 mL/min (calculated per institutional guidelines or by Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formula)

8. Corrected serum calcium of ≤11.5 mg/dL or ≤2.6 mmol/L.

9. Patient must agree to use adequate contraception methods for the duration of the study treatment and up to 4 months after the last dose of pembrolizumab administration

10. Patients must be affiliated to a Social Security System (or equivalent)

Exclusion Criteria:

1. Symptomatic central nervous system (CNS) metastases and / or carcinomatous meningitis

2. History of another malignancy within 2 years prior to study inclusion, with the exception of completely resected basal or squamous cell skin cancer, or successfully treated in-situ carcinoma

3. Prior radiotherapy in the head and neck region

4. Any prior or current treatment for invasive head and neck cancer. This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, chemotherapy, anti-PD-1/PD-L1 and CTLA-4, prior radiotherapy (RT), or use of any investigational agent

5. Uncontrolled head and neck loco-regional grade ≥3 (by CTCAE v5.0) symptoms including bleeding, pain, dysphagia (feeding tube permitted), or dyspnea (tracheotomy permitted)

6. Known Acquired Immune Deficiency Syndrome (AIDS)

7. Known currently active infection including hepatitis B or hepatitis C

8. Patient having received live attenuated vaccine within 28 days prior to enrolment

9. Pregnant or breast feeding woman

10. Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized with hormonal substitution, or psoriasis which do not require systemic treatment

11. Active immunodeficiency or ongoing immunosuppressive therapy

12. Active symptomatic interstitial lung disease

13. Significant disease which, in the judgment of the investigator, as a result of the medical interview, physical examinations, or screening investigations would make the patient inappropriate for entry into the trial

14. Any social, personal, medical, geographic and/or psychologic factor(s) that could interfere with the observance of the patient to the protocol and/or the follow-up and/or the signature of the informed consent

15. Prior organ transplantation including allogenic stem-cell transplantation

16. Other severe acute or chronic medical conditions including colitis, pneumonitis, pulmonary fibrosis or psychiatric conditions including active suicidal ideation; or laboratory abnormalities that may increase the risk associated with study participation and, in the judgment of the investigator, would make the patient inappropriate for entry into this study

17. Person deprived of their liberty or under protective custody or guardianship

18. Patient who have taken any investigational medicinal product or have used an investigational device within 30 days prior to study inclusion