Squamous cell carcinoma treated by primary surgery Stage III, stage IV (American Joint Committee on Cancer 7th edition) Oral cavity, oropharynx, hypopharynx or larynx MedDRA version: 21.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: OPDIVO
Pharmaceutical Form: Infusion
Other descriptive name: NIVOLUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Trade Name: CI
Sponsors
GORTEC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age > 18 and =65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
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 4. Incomplete macroscopic resection (R2), as stated in the surgical report 5. 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 6. Active central nervous system disease 7. Interstitial lung disease 8. Active infection 9. 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 10. Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol 11. 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 12. 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) 13. 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 14. 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 15. 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 16. Known hypersensitivity to study drugs 17. Prior organ transplantation including allogenic stem-cell transplantation 18. 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 19. Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment within 28 days prior to the first dose of study treatment 20. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness 21. Any psychiatric condition (including active suicidal ideation), or psychological, or familial, or sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule 22. Individuals deprived of liberty or placed under the authority of a tutor.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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;Secondary Objective: - To compare the overall survival (OS), loco-regional control, distant metastases of nivolumab in combination with cisplatin-RT vs SOC cisplatin-RT - To determine DFS by blinded independent central review imaging - To evaluate the overall safety and tolerability profile of nivolumab in combination with cisplatin-RT as compared to SOC cisplatin-RT - To evaluate DFS and OS by PDL-1 expression (using 28-8 assay) - To evaluate the effect of nivolumab in combination with cisplatin-RT compared to SOC cisplatin-RT on health-related quality of life - To evaluate candidate immune-related predictive biomarkers of sensitivity or insensitivity to treatment with nivolumab in pre-treatment tumor samples obtained at surgery and in blood (levels of cells, DNA, RNA, or proteins that may be related to antitumor immune response and/or disease progression) and to explore potential correlations between treatment outcome and the immune landscape.;Primary end point(s): Disease free survival (DFS by investigator imaging assessments) ;Timepoint(s) of evaluation of this end point: 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall survival - DFS by blinded independent central review - DFS and OS by PDL-1 status - Cumulative incidence of locoregional failure, cumulative incidence of distant metastatic failure and cumulative incidence of death without previous progression - 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). - 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). - Correlation between the immune landscape and patients’ outcome - Patient-Reported Outcomes (PRO): Health related quality of ife (QoL) survey will be assessed by EORTC QLQ-C30, H&N35 and EQ- 5D-5L questionnaires.;Timepoint(s) of evaluation of this end point: During treatment | — |
Countries
Belgium, France, Greece, Poland, Spain, Switzerland
Contacts
Public ContactMahasti BERT
GORTEC
Outcome results
None listed