A Trial Evaluating the Addition of Nivolumab to Cisplatin-RT for Treatment of Cancers of the Head and Neck (NIVOPOSTOP)

  • STATUS
    Recruiting
  • End date
    Sep 14, 2027
  • participants needed
    680
  • sponsor
    Groupe Oncologie Radiotherapie Tete et Cou
Updated on 14 April 2022
cancer
cavities
carcinoma
squamous cell carcinoma
neutrophil count
EGFR
nivolumab
oropharyngeal
caries
intensity-modulated radiation therapy
head and neck carcinoma
carcinoma of oropharynx
hyperhydration

Summary

The purpose of this study is to determine the efficacy of nivolumab + cisplatin-RT relative to standard of care (SOC) cisplatin-RT alone, using the disease-free survival (DFS by investigator imaging assessment) as primary endpoint )

Description

This open-label, randomized, controlled, multicenter phase III study will include 680 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.

Details
Condition Squamous Cell Carcinoma of Head and Neck
Treatment cisplatin, Nivolumab, RT
Clinical Study IdentifierNCT03576417
SponsorGroupe Oncologie Radiotherapie Tete et Cou
Last Modified on14 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Age > 18 and < 75 years
Performance Status (PS) ECOG 0-1 (Appendix 2)
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
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
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
For oropharyngeal tumor, known p16 status (by IHC)
Adequate tumor specimen from archived or resected tissue available for PD-L1, TILs and
immune landscape and other biomarker evaluation
Patient's ability to receive cisplatin 100 mg/m2 for 3 cycles
Creatinine Cclearance (CrCl) ≥ 60 mL/min (measured or calculated by Cockcroft and Gault method) or estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73m2 (determined by CKDEPI or MDRD method). The highest value should be considered if both are assessed
No hearing loss (assessed clinically and confirmed by audiogram if doubtful)
Absolute neutrophil count ≥1 500/mm3, platelets ≥100 000/mm3, haemoglobin ≥ 9 g/dL, aspartate transaminase (AST) and alanine transaminase (ALT) less than 2.5 times the upper limit of the normal range (ULN), total bilirubin ≤ 1.5 mg/dL(except Gilbert Syndrom: < 3.0 mg/dL)
Cardiac function compatible with hyperhydration
Peripheral neuropathy ≤ grade 1
No administration of prophylactic phenytoin
Patients aged 71-74 years,must be fit according to geriatric evaluation

Exclusion Criteria

Nasopharyngeal, paranasal sinuses, nasal cavity tumours or thyroid cancers
Squamous cell carcinoma involving cervical neck nodes with unknown primary site
Metastatic disease
Incomplete macroscopic resection (R2), as stated in the surgical report
Known active viral infection Human Immunodeficiency Virus (HIV), Hepatitis B/C) or known history of positive test for HIV, active autoimmune disease and/or an active immunodeficiency or ongoing immunosuppressive therapy
Active Central Nervous System disease
Interstitial lung disease
Active infection
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
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 5 months after the last dose of nivolumab
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
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
Known hypersensitivity to study drugs
Prior organ transplantation including allogenic stem-cell transplantation
Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment within 28 days prior to the first dose of study treatment
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
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
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
Individuals deprived of liberty or placed under the authority of a tutor
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note