Randomized trial evaluating the addition of nivolumab to cisplatin-radiotherapy combination for treatment of cancers of the head and neck

Trial details

Who runs it

Groupe Oncologie Radiotherapie Tete Cou

Trial code

EU 2024-513206-65-00

Record updated

2025. március 31.

Original description

To determine the efficacy of nivolumab + cisplatin-RT relative to SOC cisplatin-RT alone, using the disease-free survival (DFS by investigator imaging assessment) as primary endpointRead full original descriptionShow less

A phase III randomized trial of post-operative adjuvant nivolumab and concomitant chemo-radiotherapy in high-risk patients with resected squamous cell carcinoma of head and neck (SCCHN)

To determine the efficacy of nivolumab + cisplatin-RT relative to SOC cisplatin-RT alone, using the disease-free survival (DFS by investigator imaging assessment) as primary endpoint

Inclusion: Age > 18 and < 75 years; Squamous cell carcinoma of the head and neck treated by primary surgery; Histopathological classification: pStage III or IV. However, Oropharyngeal Cancer pStage II p16 positive with pT3N1 or pT4N1 and tobacco consumption ≥20 packs/year are eligible. (American Joint Committee on Cancer 8th edition); Subject must have complete macroscopic resection; Subject must be free of disease; Recovery from the surgical procedure allowing for cisplatin-Radiotherapy; Radiotherapy planned to start within 4 to 9 weeks after surgery. However, a maximum of 1 additional week could be considered in case of delay due to healing or logistical problem; Patient/tumor carrying a high risk of relapse with one or more following criteria: · Extra-capsular extension (ECE) · Multiple peri-neural invasion · Multiple nodal extension without ECE (≥ 4 nodes) · Positive margins (R1 or close margin ≤ 1 mm) R1 is microscopic residual disease and close margin is R0 with a minimum margin ≤ 1 mm in any direction; Adequate tumor specimen from archived or resected tissue available for PD-L1, TILs and immune landscape and other biomarker evaluation; Performance Status (PS) ECOG 0-1; Written informed consent; Recording of alcohol consumption and smoking history; Histologically proven squamous cell carcinoma of the head and neck from one or more of the following primary sites: oral cavity, oropharynx, hypopharynx or larynx.

Exclusion: Incomplete macroscopic resection (R2), as stated in the surgical report; Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol; 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; Any prior treatment for the current head and neck cancer other than primary surgery. 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; Clinically significant (i.e., active) cardiovascular disease: · Cerebral vascular accident/stroke (< 6 months prior to enrollment) or · Myocardial infarction (< 6 months prior to enrollment) or · unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II) or · Serious cardiac arrhythmia requiring medication; Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers; Active central nervous system disease; Interstitial lung disease; Active infection; Metastatic disease; Known active viral infection (Human Immunodeficiency Virus (HIV), Hepatitis B/C) or known history of positive test for HIV, active autoimmune disease and/or active immunodeficiency or ongoing immunosuppressive therapy; 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); Severe acute or chronic medical conditions including colitis, pneumonitis, pulmonary fibrosis, laboratory abnormalities or other 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; Squamous cell carcinoma involving cervical neck nodes with unknown primary site; 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 5 months after the last dose of nivolumab; Male patients who are unwilling or unable to use contraception methods for the duration of the study and for at least 6 months after the last dose of cisplatin.

EU CTIS 2024-513206-65-00