NIVOLUMAB for Head and neck squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- Age > 18 and < 75 years"}
• {"criterion_text":"- Squamous cell carcinoma of the head and neck treated by primary surgery"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Subject must have complete macroscopic resection."}
• {"criterion_text":"- Subject must be free of disease"}
• {"criterion_text":"- Recovery from the surgical procedure allowing for cisplatin-Radiotherapy"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Adequate tumor specimen from archived or resected tissue available for PD-L1, TILs and immune landscape and other biomarker evaluation"}
• {"criterion_text":"- Performance Status (PS) ECOG 0-1"}
• {"criterion_text":"- Written informed consent"}
• {"criterion_text":"- Recording of alcohol consumption and smoking history"}
• {"criterion_text":"- 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 criteria

• {"criterion_text":"- Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers"}
• {"criterion_text":"- Incomplete macroscopic resection (R2), as stated in the surgical report"}
• {"criterion_text":"- Squamous cell carcinoma involving cervical neck nodes with unknown primary site"}
• {"criterion_text":"- Active central nervous system disease"}
• {"criterion_text":"- Interstitial lung disease"}
• {"criterion_text":"- Active infection"}
• {"criterion_text":"- Metastatic disease"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}

Primary endpoints

• {"endpoint_text":"- Disease free survival (DFS by investigator imaging assessments) defined as the time between the date of randomization and the date of first loco-regional or distant recurrence or death (of any cause) whichever occurs first,..","definition_or_measurement_approach":"Defined as time between date of randomization and date of first loco-regional or distant recurrence or death (any cause); assessed by investigator imaging assessments."}

Secondary endpoints

• {"endpoint_text":"- Overall survival","definition_or_measurement_approach":"Overall survival (OS) measured as time from randomization to death from any cause."}
• {"endpoint_text":"- DFS by blinded independent central imaging review","definition_or_measurement_approach":"Disease-free survival evaluated by blinded independent central review of imaging."}
• {"endpoint_text":"- DFS and OS by PDL-1 status","definition_or_measurement_approach":"Analysis of DFS and OS stratified by PD-L1 expression (using 28-8 assay)."}
• {"endpoint_text":"- Cumulative incidence of locoregional failure, cumulative incidence of distant metastatic failure and cumulative incidence of death without previous progression","definition_or_measurement_approach":"Cumulative incidence functions for locoregional failure, distant metastatic failure, and death without prior progression."}
• {"endpoint_text":"- Incidence of second primary malignancy (SCC to a distance >= 3 cm from the tumor bed and that will clearly not be attributable to a relapse or a second cancer arising outside the upper aero digestive track).","definition_or_measurement_approach":"Incidence of second primary malignancies meeting specified criteria (SCC ≥3 cm from tumor bed and not attributable to relapse)."}
• {"endpoint_text":"- Safety: Adverse events and laboratory abnormalities as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0). Incidence of delayed toxicity of radiotherapy (e.g. dysphagia, chronic swallowing dysfunctions, speech problems, cervical fibrosis, rate and duration of the use of feeding tubes).","definition_or_measurement_approach":"Safety assessed by AE reporting and laboratory abnormalities graded per NCI-CTCAE v5.0; delayed radiotherapy toxicities (specified symptomatic endpoints) recorded (incidence, rate and duration of feeding tube use)."}
• {"endpoint_text":"- Correlation between the immune landscape and patients’ outcome","definition_or_measurement_approach":"Exploratory correlation analyses between immune-related biomarkers (tumor and blood) and clinical outcomes."}

Belgium

Earliest CTIS Part Ii Submission Date

18-06-2024

Latest Decision Or Authorization Date

24-07-2024

Processing Time Days

36

Number Of Sites

3

Number Of Participants

11

France

Earliest CTIS Part Ii Submission Date

27-06-2024

Latest Decision Or Authorization Date

20-03-2025

Processing Time Days

266

Number Of Sites

63

Number Of Participants

595

Greece

Earliest CTIS Part Ii Submission Date

14-08-2024

Latest Decision Or Authorization Date

12-09-2024

Processing Time Days

29

Number Of Sites

1

Number Of Participants

6

Poland

Earliest CTIS Part Ii Submission Date

18-06-2024

Latest Decision Or Authorization Date

25-07-2024

Processing Time Days

37

Number Of Sites

2

Number Of Participants

12

Spain

Earliest CTIS Part Ii Submission Date

18-06-2024

Latest Decision Or Authorization Date

31-03-2025

Processing Time Days

286

Number Of Sites

18

Number Of Participants

51

Primary sponsor

Full Name

Groupe Oncologie Radiotherapie Tete Cou

Organisation Type

Patient organisation/association

Country Of Registered Address

France