Essai de Phase III randomisé évaluant l’ajout de nivolumab à l’association cisplatine-radiothérapie (traitement standard) dans le cancer épidermoïde de la tête et du cou localement avancé opéré à risque élevé de récidive

Drug: Cisplatin
Drug: Nivolumab
Radiation: RT

Inclusion Criteria: 1. Age > 18 and < 75 years 2. Performance Status (PS) ECOG 0-1 (Appendix 2) 3. Written informed consent 4. Recording of alcohol consumption and smoking history 5. Stage III, stage IV (American Joint Committee on Cancer 7th edition) 38 6. Oral cavity, oropharynx, hypopharynx or larynx 7. Squamous cell carcinoma treated by primary surgery 8. Recovery from the surgical procedure allowing for cisplatin-RT 9. RT planned within 4 to 8 weeks after surgery 10. Patient/tumor carrying a high risk of relapse with: - extra-capsular extension (ECE), - and/or positive margins (R1 or close margin = 1 mm) 11. Availability of surgical tumour specimen (PD-L1, TILs and immune landscape ...) 12. For oropharyngeal tumor, known p16 status (by IHC) 13. Determination of patient ability to receive cisplatin 100 mg/m2 for 3 cycles: - Calculated creatinine clearance = 60 mL/min as determined by CKD-EPI method (Cockcroft and Gault or MDRD method allowed) - Absolute neutrophil count =1 500/µL, platelets =100 000/µL, haemoglobin = 10 g/dL, aspartate (AST) and alanine transaminase (ALT) less than 2 times the upper limit of the normal range (ULN), total bilirubin = 1.5 mg/dL, serum albumin >35 g/L - Peripheral neuropathy = grade 1 - Sensorineural hearing loss (confirmed by audiogram) - Cardiac function compatible with hyperhydration - No administration of prophylactic phenytoin - For ppatients aged 71-74 years, PS must be 0 and fit according to geriatric evaluation Exclusion Criteria: 1. Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers 2. Squamous cell carcinoma involving cervical neck nodes with unknown primary site 3. Metastatic disease (stage IVc) 4. Active viral infection (HIV, Hepatitis B/C) or known history of positive test for HIV 5. Active autoimmune disease 6. Active immunodeficiency or ongoing immunosuppressive therapy 7. Active CNS disease 8. Interstitial lung disease 9. Active infection 10. 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, induction chemotherapy, prior RT, or use of any investigational agent 11. Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol 12. Concomitant treatment with any drug on the prohibited medication list such as live vaccines. Live vaccines administered more than 30 days before study entry are permitted 13. History of other malignancy within the last 3 years (exception of in situ carcinoma, thyroid papillary carcinoma, skin carcinomas, localized prostate carcinoma Gleason 6 and in situ breast carcinoma) 14. Pregnant, breastfeeding patients, and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in the protocol for the duration of the study and for at least 6 months after the last dose of cisplatin and 7 months after the last dose of nivolumab 15. 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 16. Known hypersensitivity reaction to study drugs 17. Any social, personal, medical 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 18. Prior organ transplantation including allogenic stem-cell transplantation 19. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication 20. Persisting toxicity related to prior therapy or pre-existing conditions (NCI CTCAE v. 4.03 Grade > 1) 39 21. 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 22. Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment within 28 days prior to the first dose of study treatment
Minimum age: 18 Years
Maximum age: 74 Years
Sex: All