| Eligibility |
Inclusion Criteria:
1. Age > 18 years with no upper limit
2. Performance Status ECOG 0-2
3. Squamous cell carcinoma, previously untreated
4. T1-T4 with clinical status N0-N1 or N2a-N2b non palpable, with only homolateral lymph
node in radiological examinations.
5. Patient with at least one of these fragility criteria :
o Status ECOG 1 with multiple comorbidities, at least 2 pathologies with grade = 2
(renal and/or cardiac and/or vascular and/or hepatic, and/or,neurologic, and/or
pulmonary)
o Status ECOG = 2
o Age = 70 , judged unfit with oncogeratric evaluation by EGE (ELAN Geriatric
Evaluation) test or unable to receive cisplatine or Carboplatine- 5FU (at least one
criteria listed below*)
* Criteria for determining if a patient is unfit for receiving cisplatine or carbo-5FU
:
- Calculated creatinine clearance = 60 mL/min as determined by the modified. method of
Cockcroft and Gault or glomerular filtration rate = 60 mL/min/1.73m² (CKD-EPI method
recommended)
- Haemoglobin < 10 g/dL, aspartate (AST) and alanine transaminase (ALT) more than 2
times the upper limit of the normal range (ULN), serum albumin =35 g/L, Absolute
neutrophil count = 1 500/µL, platelets = 100 000/µL or total bilirubin = 1.5 mg/dL
- Cardiac function not compatible with hyperhydration or significant heart disease
- Weight loss > 15% in 2 months
6. Oral cavity, oropharynx, hypopharynx or larynx
7. Availability of pre-treatment tumor tissue sample (for PD-L1 expression, TILs and
immune landscape)
8. Documentation of p16 disease (HPV status for oropharyngeal tumor)
9. Recording of alcohol consumption and smoking history
10. Glomerular filtration rate (GFR) >40 mL/min/1.73m2 (CKD-EPI method recommended) or
Calculated creatinine clearance CL>40 mL/min by the Cockcroft-Gault formula
11. Patient willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations during the follow
up period
12. Patient able to understand French and complete the quality of life questionnaires or
who can be helped by a support person if necessary.
13. Must have a life expectancy of at least 12 weeks
14. Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal patients. Women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply:
1) Women <50 years of age would be considered post-menopausal if they have been amenorrheic
for 12 months or more following cessation of exogenous hormonal treatments and if they have
luteinizing hormone and folliclestimulating hormone levels in the post-menopausal range for
the institution or underwent surgical sterilization (bilateral oophorectomy or
hysterectomy).
2) Women =50 years of age would be considered post-menopausal if they have been amenorrheic
for 12 months or more following cessation of all exogenous hormonal treatments, had
radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced
menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral
oophorectomy, bilateral salpingectomy or hysterectomy).
15. Written informed consent obtained prior to performing any protocol-related procedures,
including screening evaluations
Exclusion Criteria:
1. Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers
2. Metastatic disease
3. Active CNS disease
4. Any prior or current treatment for invasive head and neck cancer
5. Any unresolved toxicity NCI CTCAE v5.0 Grade =2 from previous anticancer therapy with
the exception of alopecia, vitiligo, and the laboratory values defined in the
inclusion criteria.
1. Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis
2. Patients with irreversible toxicity not reasonably expected to be exacerbated by
treatment with durvalumab may be included only after consultation with the
investigator
6. Major surgical procedure (as defined by the investigator) within 28 days prior to the
first dose of IP. Note: Local surgery of isolated lesions for palliative intent is
acceptable
7. History of leptomeningeal carcinomatosis
8. Body weight = 30 kg and/or weight loss of = 15% during the last 4 weeks (except if
renutrition with a feeding tube is planned before the onset of treatment or is
ongoing)
9. Concurrent treatment with any other systemic anti-cancer therapy that is not specified
in the protocol
10. Concomitant treatment with any drug on the prohibited medication list such as live
vaccines within 30 days prior to the first dose of IP
11. Known allergy or hypersensitivity reaction to study drug or any of the study drug
excipients
12. Prior organ transplantation including allogenic stem-cell transplantation
13. Other severe acute or chronic medical conditions including pneumonitis, pulmonary
fibrosis
14. Active autoimmune or inflammatory disorders (including inflammatory bowel disease
[e.g., colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease,
rheumatoid arthritis, hypophysitis, uveitis, etc])
15. Uncontrolled intercurrent illness, including but not limited to, symptomatic
congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac
arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions, or
psychiatric illness/social situations that would limit compliance with study
requirement, substantially increase risk of incurring AEs or compromise the ability of
the patient to give written informed consent
16. History of another primary malignancy except for:
1. Malignancy treated with curative intent and with no known active disease = 5
years
2. Adequately treated non-melanoma skin cancer
3. Adequately treated carcinoma in situ without evidence of disease
17. History of active primary immunodeficiency
18. Ongoing or active infection including tuberculosis, hepatitis B (known positive HBV
surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus
(positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined
as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are
eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if
polymerase chain reaction is negative for HCV RNA
19. Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections
2. Systemic corticosteroids < 10 mg/day of prednisone or its equivalent
3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
20. Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy
21. Prior randomization or treatment in a previous durvalumab clinical study regardless of
treatment arm assignment
22. Individual deprived of liberty, or under any kind of guardianship
23. Inclusion in another study research on drug or medical device
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