Etude : NIVOPOSTOP /



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Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : NIVOPOSTOP

Nom :

Traitement : Adjuvant / Radiothérapie

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 05/08/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : 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 (SCCHN) localement avancé opéré, à risque élevé de récidive

Spécialité : Lèvre, cavité buccale et pharynx
Localisation : C06 - Tumeur maligne de la bouche, parties autres et non précisées

Spécialité : Lèvre, cavité buccale et pharynx
Localisation : C10 - Tumeur maligne de l'oropharynx

Spécialité : Lèvre, cavité buccale et pharynx
Localisation : C13 - Tumeur maligne de l'hypopharynx

Spécialité : Organes respiratoires et intrathoraciques
Localisation : C32 - Tumeur maligne du larynx
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : This open-label, randomized, controlled, multicenter phase III study will include 484 patients who have been operated for their LA SCCHN and exhibiting extra capsular extension (ECE) and/or positive margins (high risk). Subjects will be randomized (1:1) to receive post-operative concomitant cisplatin-RT with or without nivolumab.

The study is designed with the general objective of demonstrating that treatment with nivolumab in combination with 3 cycles of cisplatin during RT is more efficient and not more toxic than the SOC 3 cycles of cisplatin during RT.

Stratification will be based on the P16 status (immunohistochemistry assay on surgical sample). Two classes: Oropharyngeal Cancer (OPC) p16 positive versus OPC p16 negative or not OPC.

2 arms:
- Active Comparator: RT+ cisplatin
100 mg/m2 of cisplatin on days 1, 22,43 of RT
- Experimental: RT+ cisplatin + nivolumab
360 mg of nivolumab 3 weeks before RT-Cisplatin
360 mg of nivolumab on days 1, 22,43 of -RT-cisplatin

Phase : III

Stade : Localement avancé à Métastatique

NA
Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Age > 18 and < 75 years
- Performance Status (PS) ECOG 0-1 (Appendix 2)
- Written informed consent
- Recording of alcohol consumption and smoking history
- Stage III, stage IV (American Joint Committee on Cancer 7th edition) 38
- Oral cavity, oropharynx, hypopharynx or larynx
- Squamous cell carcinoma treated by primary surgery
- Recovery from the surgical procedure allowing for cisplatin-RT
- RT planned within 4 to 8 weeks after surgery
- Patient/tumor carrying a high risk of relapse with:
-> extra-capsular extension (ECE),
-> and/or positive margins (R1 or close margin ≤ 1 mm)
- Availability of surgical tumour specimen (PD-L1, TILs and immune landscape ...)
- For oropharyngeal tumor, known p16 status (by IHC)
- 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 patients aged 71-74 years, PS must be 0 and fit according to geriatric evaluation

Critères de non-inclusion : - Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers
- Squamous cell carcinoma involving cervical neck nodes with unknown primary site
- Metastatic disease (stage IVc)
- Active viral infection (HIV, Hepatitis B/C) or known history of positive test for HIV
- Active autoimmune disease
- Active immunodeficiency or ongoing immunosuppressive therapy
- Active CNS disease
- Interstitial lung disease
- Active infection
- 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
- 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
- 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)
- 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
- 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
- Known hypersensitivity reaction to study drugs
- 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
- Prior organ transplantation including allogenic stem-cell transplantation
- 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
- Persisting toxicity related to prior therapy or pre-existing conditions (NCI CTCAE v. 4.03 Grade > 1) 39
- 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
- Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment within 28 days prior to the first dose of study treatment
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03576417
Promoteur :
Groupe Oncologie Radiothérapie Tête et Cou (GORTEC)
Type de sponsor : Institutionnel
37000 TOURS

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre François BACLESSE - 3 avenue du Général Harris - 14000 CAEN

Investigateur :
Dominique DE RAUCOURT

TEC / ARC / IDE :
Karim HAMOND
k.hamond@
baclesse.unicancer.fr

Ouverture de l'essai : OUVERT

MAJ : 05/08/2019